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CompletedNCT03091920Updated Aug 31, 2020Results posted

Trial of IW-1973, A Stimulator of Soluble Guanylate Cyclase (sGC) in Patients With Stable Type 2 Diabetes and Hypertension

A Phase 2 interventional study of IW-1973 and Placebo in Diabetes Mellitus, Type 2 and Hypertension, sponsored by Cyclerion Therapeutics. Completed at 1 site in United States. Open to participants aged 30 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-08-31.

Sponsored by Cyclerion Therapeutics (formerly part of Ironwood Pharmaceuticals, Inc.) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
30 Years to 75 Years
Sex
All
01

Study summary

To compare the safety, tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) effects of 2 treatment regimens of IW-1973 tablet (40 mg per day) administered orally for 2 weeks to patients with stable type 2 diabetes mellitus and hypertension.

02

Conditions studied

  • Diabetes Mellitus, Type 2
  • Hypertension
03

In context

Diabetes Mellitus, Type 2

10,371 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,406 are open to participants now.

This study's enrollment of 26 is below the median of 80 across 8,350 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

Cyclerion Therapeutics is the lead sponsor of 11 studies on the registry; none are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.

First submitted before Cyclerion Therapeutics left Ironwood Pharmaceuticals, Inc..

Browse Cyclerion Therapeutics studies →All Ironwood Pharmaceuticals, Inc. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patient is ambulatory male or female
  • Patient's score is > 20 and \< 40 kg/m\^2 at the Screening Visit
  • Women of must have a negative pregnancy test at the time of screening and check-in and must agree to use protocol-specified throughout the duration of the study
  • Patient's health is stable with no findings on physical examination
  • Patient has type 2 (ie, adult onset) diabetes mellitus diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit, is on a stable glycemic control medication, and protocol specified (Hb)A1c values at the Screening Visit
  • Patient has hypertension diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit, and blood pressure (BP) within the protocol's acceptable range
  • Patients must be on a stable regimen for hypertension control that includes an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), stable for 28 days
  • Other inclusion criteria per protocol

Exclusion criteria

Exclusion Criteria:

  • Patient has a active or unstable medical condition that, in the opinion of the Investigator, would preclude trial participation
  • Patient is on medication(s) that, when co-administered with a sGC stimulator, could increase the risk of hypotension
  • Patient has evidence of severe or active end-organ damage
  • Patient is an active smoker or has used any nicotine-containing products (cigarettes, e-cigarettes, vape pens, cigars, chewing tobacco, gum, patches) during the 6 months before Check-in. Use of nicotine is excluded during the study until after the End of Trial Visit.
  • Other exclusion criteria per protocol
Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    IW-1973 QD/QD

    On Days 1-14: IW-1973 40 mg taken once daily (QD) in morning (AM) and placebo taken QD at night (PM).

    Drug: IW-1973 · Drug: Placebo

  • Experimental
    IW-1973 BID (Twice Daily)/QD

    On Days 1-7: IW-1973 20 mg taken in AM and IW-1973 20 mg taken in PM. On Days 8-14: IW-1973 40 mg taken QD in AM and placebo taken QD in PM.

    Drug: IW-1973 · Drug: Placebo

  • Placebo comparator
    Placebo

    On Days 1-14: Placebo taken in AM and in PM.

    Drug: Placebo

Interventions

  • DrugIW-1973

    Oral Tablet

  • DrugPlacebo

    Oral Tablet

06

What researchers measure

Primary outcomes

  1. Change From Study Baseline Over Time in Supine Systolic Blood Pressure

    Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42

  2. Change From Study Baseline Over Time in Supine Diastolic Blood Pressure

    Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42

  3. Change From Study Baseline Over Time in Supine Pulse

    Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42

  4. Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time

    Time frame: Baseline, Days 1-14, Day 15, 21, 42

  5. Orthostatic Systolic Blood Pressure Over Time

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

    Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM

  6. Orthostatic Diastolic Blood Pressure Over Time

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

    Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM

  7. Orthostatic Pulse Over Time

    An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

    Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM

  8. Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure

    24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  9. Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure

    Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  10. Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure

    Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  11. Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure

    Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

    Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose

  12. Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure

    24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  13. Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure

    Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  14. Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure

    Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  15. Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure

    Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

    Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose

  16. Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure

    24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  17. Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure

    Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  18. Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure

    Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  19. Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure

    Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

    Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose

  20. Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse

    24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  21. Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse

    Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  22. Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse

    Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

    Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14

  23. Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse

    Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

    Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose

  24. Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13

    RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values \>1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.

    Time frame: Baseline, Day 13 predose AM

  25. Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay

    Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with \< 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \< 180 units indicate impairment of platelet aggregation.

    Time frame: Baseline, Day 8, Day 14

  26. Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay

    Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or \> 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.

    Time frame: Baseline, Day 8, Day 14

  27. Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay

    The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \<180 PRU indicate impairment of platelet aggregation.

    Time frame: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)

  28. Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay

    Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.

    Time frame: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)

  29. Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin

    Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.

    Time frame: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15

  30. IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7

    Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.

    Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose

  31. IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7

    Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose

  32. IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7

    Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose

  33. IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7

    Time frame: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose

  34. IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14

    Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose

  35. IW-1973 Pharmacokinetics: AUCtau on Day 14

    Time frame: Day 14: 1, 3, 6h (± 5 min) postdose

  36. IW-1973 Pharmacokinetics: Tmax on Days 8 and 14

    Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose

  37. IW-1973 Pharmacokinetics: Cmax on Days 8 and 14

    Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose

  38. IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14

    Time frame: Days 13 and 14: predose

  39. IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14

    Time frame: Day 14: 1, 3, 6h (± 5 min) postdose

  40. IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14

    Time frame: Day 14: 1, 3, 6h (± 5 min) postdose

  41. IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)

    Time frame: Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42)

  42. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs

    An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.

    Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)

  43. Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results

    Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)

  44. Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values

    Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine diastolic blood pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine heart rate (SHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ \> 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ \> 15 mmHg from supine to standing. Orthostatic HR: ↓ \> 30 bpm from supine to standing.

    Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)

  45. Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings

    Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.

    Time frame: Post-randomization to End of Trial Visit (42 [± 3] days)

  46. Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results

    Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)

  47. Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)

    Time frame: Study Baseline, Day 15/Discharge, Day 42/End of Trial

07

Results

Posted Aug 31, 2020

Participant flow

Participant flow — Overall Study
MilestonePlaceboIW-1973 40 mg Twice Dily (BID)/Once Daily (QD)IW-1973 40 mg QD/QD
Started61010
Completed6910
Not completed010
Withdrew: Adverse event010

Outcome measures

PrimaryChange From Study Baseline Over Time in Supine Systolic Blood Pressure
Time frame:
Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Reported as:
Least squares mean · mmHg
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline (Day 1 predose AM)130.2 ± 11.1120.1 ± 8.9128.6 ± 10.1
Day 1 postdose AM: 1 hour-6.8 ± 4.8-7.7 ± 3.9-6.2 ± 3.7
Day 1 postdose AM: 4 hour4.4 ± 6.0-9.5 ± 4.9-11.1 ± 4.6
Day 1 postdose AM: 8 hour0.5 ± 5.0-9.4 ± 4.0-2.7 ± 3.8
Day 1 predose PM1.8 ± 6.3-6.9 ± 5.1-1.7 ± 4.8
Day 1 postdose PM: 1 hour-0.6 ± 5.6-3.9 ± 4.5-5.0 ± 4.3
Day 2 predose AM5.5 ± 3.5-2.9 ± 2.8-0.2 ± 2.7
Day 2 postdose AM: 1 hour2.0 ± 4.6-13.4 ± 3.7-7.4 ± 3.5
Day 2 postdose AM: 4 hour1.7 ± 6.1-7.1 ± 4.9-9.4 ± 4.7
Day 2 predose PM4.6 ± 4.5-7.1 ± 3.6-2.4 ± 3.4
Day 2 postdose PM: 1 hour-3.8 ± 5.3-2.2 ± 4.3-3.1 ± 4.1
Day 2 postdose PM: 4 hour-5.0 ± 4.2-9.7 ± 3.4-8.0 ± 3.3
Day 3 predose AM-0.8 ± 4.0-5.5 ± 3.2-6.5 ± 3.1
Day 3 postdose PM: 4 hour-5.8 ± 4.8-6.0 ± 3.9-8.6 ± 3.7
Day 4 predose AM-0.8 ± 3.3-7.0 ± 2.7-8.9 ± 2.6
Day 5 predose AM-0.2 ± 3.6-1.9 ± 2.9-10.3 ± 2.8
Day 6 predose AM-4.3 ± 4.1-11.0 ± 3.3-8.6 ± 3.2
Day 7 predose AM-4.3 ± 4.8-3.3 ± 3.8-8.1 ± 3.7
Day 7 postdose AM: 1 hour-5.3 ± 4.4-8.4 ± 3.5-11.7 ± 3.4
Day 7 postdose AM: 4 hour1.3 ± 4.8-8.2 ± 3.9-15.9 ± 3.7
Day 8 predose AM3.7 ± 4.6-8.0 ± 3.7-4.7 ± 3.6
Day 8 postdose AM: 1 hour-2.0 ± 5.3-15.4 ± 4.3-12.3 ± 4.1
Day 8 postdose AM: 4 hour-5.2 ± 6.1-15.2 ± 4.9-9.8 ± 4.7
Day 8 predose PM-4.5 ± 5.5-8.8 ± 4.4-5.8 ± 4.2
Day 9 predose AM3.0 ± 3.7-9.7 ± 3.0-2.1 ± 2.9
Day 10 predose AM-1.3 ± 4.0-9.3 ± 3.2-5.1 ± 3.0
Day 11 predose AM3.8 ± 5.4-12.3 ± 4.4-4.5 ± 4.2
Day 12 predose AM-6.5 ± 4.1-9.8 ± 3.3-12.0 ± 3.1
Day 13 predose AM-1.6 ± 3.7-13.5 ± 3.0-8.1 ± 2.8
Day 13 postdose AM: 1 hour-2.4 ± 4.0-16.6 ± 3.2-14.2 ± 3.1
Day 13 postdose AM: 4 hour-3.9 ± 6.3-15.6 ± 5.1-13.7 ± 4.8
Day 13 predose PM-1.9 ± 4.0-13.2 ± 3.2-11.8 ± 3.1
Day 14 predose AM-3.7 ± 5.9-9.5 ± 4.7-9.8 ± 4.5
Day 15/Discharge2.1 ± 4.9-6.0 ± 4.0-3.0 ± 3.8
Day 21/Follow-Up-3.5 ± 4.31.3 ± 3.51.7 ± 3.3
Day 42/End of Trial3.3 ± 6.28.8 ± 5.0-1.2 ± 4.8
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Ls mean difference: -0.9 · 95% CI -14.2 to 12.4LS mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.6 · 95% CI -11.8 to 12.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -13.9 · 95% CI -30.6 to 2.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -15.5 · 95% CI -31.0 to 0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.9 · 95% CI -23.8 to 3.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.1 · 95% CI -16.0 to 9.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.8 · 95% CI -26.2 to 8.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.6 · 95% CI -19.7 to 12.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.3 · 95% CI -18.7 to 12.2
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.4 · 95% CI -18.7 to 9.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.5 · 95% CI -18.2 to 1.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.7 · 95% CI -14.8 to 3.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -15.4 · 95% CI -28.1 to -2.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -9.4 · 95% CI -21.1 to 2.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.8 · 95% CI -25.6 to 7.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -11.2 · 95% CI -26.7 to 4.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -11.7 · 95% CI -24.0 to 0.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -7.0 · 95% CI -18.4 to 4.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.6 · 95% CI -13.0 to 16.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.7 · 95% CI -12.9 to 14.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.7 · 95% CI -16.4 to 7.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.0 · 95% CI -13.9 to 7.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.7 · 95% CI -15.8 to 6.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.8 · 95% CI -16.0 to 4.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.2 · 95% CI -13.6 to 13.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.8 · 95% CI -15.2 to 9.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.2 · 95% CI -15.5 to 3.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.1 · 95% CI -16.6 to 0.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.7 · 95% CI -11.8 to 8.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -10.0 · 95% CI -19.4 to -0.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.7 · 95% CI -18.1 to 4.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.3 · 95% CI -14.8 to 6.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.0 · 95% CI -12.2 to 14.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.8 · 95% CI -16.0 to 8.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.0 · 95% CI -15.1 to 9.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.4 · 95% CI -17.6 to 4.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.5 · 95% CI -22.7 to 3.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -17.2 · 95% CI -29.5 to -5.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -11.7 · 95% CI -24.4 to 1.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.3 · 95% CI -20.2 to 3.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -13.4 · 95% CI -28.1 to 1.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -10.3 · 95% CI -24.0 to 3.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -10.1 · 95% CI -27.0 to 6.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.6 · 95% CI -20.4 to 11.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.2 · 95% CI -19.5 to 11.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.3 · 95% CI -15.4 to 12.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -12.7 · 95% CI -23.0 to -2.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.2 · 95% CI -14.7 to 4.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.0 · 95% CI -19.0 to 2.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.8 · 95% CI -14.0 to 6.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -16.1 · 95% CI -31.0 to -1.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.3 · 95% CI -22.1 to 5.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.4 · 95% CI -14.6 to 7.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.5 · 95% CI -15.9 to 4.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -11.9 · 95% CI -22.1 to -1.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.5 · 95% CI -16.0 to 2.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -14.3 · 95% CI -25.4 to -3.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -11.8 · 95% CI -22.1 to -1.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -11.7 · 95% CI -29.0 to 5.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -9.8 · 95% CI -25.9 to 6.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -11.3 · 95% CI -22.4 to -0.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -9.9 · 95% CI -20.2 to 0.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.8 · 95% CI -22.0 to 10.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.1 · 95% CI -21.1 to 9.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.1 · 95% CI -21.7 to 5.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.0 · 95% CI -17.7 to 7.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.8 · 95% CI -7.0 to 16.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.2 · 95% CI -5.8 to 16.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.5 · 95% CI -11.7 to 22.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.5 · 95% CI -20.4 to 11.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Study Baseline Over Time in Supine Diastolic Blood Pressure
Time frame:
Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Reported as:
Least squares mean · mmHg
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline (Day 1 predose AM)80.3 ± 6.975.5 ± 4.474.8 ± 5.9
Day 1 postdose AM: 1 hour-3.1 ± 2.4-5.7 ± 1.8-5.1 ± 1.8
Day 1 postdose AM: 4 hour-0.3 ± 2.4-3.2 ± 1.8-7.4 ± 1.8
Day 1 postdose AM: 8 hour0.9 ± 2.3-4.6 ± 1.7-3.7 ± 1.7
Day 1 predose PM-1.3 ± 2.2-4.9 ± 1.6-3.5 ± 1.6
Day 1 postdose PM: 1 hour-0.9 ± 3.4-5.9 ± 2.5-3.7 ± 2.5
Day 2 predose AM3.1 ± 2.0-1.3 ± 1.50 ± 1.5
Day 2 postdose AM: 1 hour-1.4 ± 2.4-8.1 ± 1.8-6.7 ± 1.8
Day 2 postdose AM: 4 hour2.2 ± 3.4-3.1 ± 2.5-6.2 ± 2.5
Day 2 predose PM1.9 ± 2.3-3.7 ± 1.7-2.6 ± 1.7
Day 2 postdose PM: 1 hour-2.2 ± 2.6-2.7 ± 1.9-4.4 ± 1.9
Day 2 postdose PM: 4 hour-3.9 ± 2.7-6.3 ± 2.0-5.4 ± 2.0
Day 3 predose AM-0.8 ± 2.5-0.6 ± 1.8-0.5 ± 1.8
Day 3 postdose PM: 4 hour-5.5 ± 3.0-4.0 ± 2.2-6.7 ± 2.2
Day 4 predose AM0.3 ± 2.2-4.0 ± 1.6-4.2 ± 1.6
Day 5 predose AM1.8 ± 2.2-0.6 ± 1.6-5.3 ± 1.6
Day 6 predose AM-0.5 ± 1.9-3.3 ± 1.4-5.2 ± 1.4
Day 7 predose AM0.9 ± 2.9-3.2 ± 2.1-3.4 ± 2.1
Day 7 postdose AM: 1 hour-1.7 ± 2.4-6.0 ± 1.8-7.4 ± 1.8
Day 7 postdose AM: 4 hour-6.1 ± 3.5-5.1 ± 2.6-5.9 ± 2.6
Day 8 predose AM0.6 ± 2.7-3.9 ± 1.9-2.2 ± 2.0
Day 8 postdose AM: 1 hour0 ± 2.4-9.3 ± 1.8-8.3 ± 1.8
Day 8 postdose AM: 4 hour-3.6 ± 2.8-8.9 ± 2.0-4.9 ± 2.1
Day 8 predose PM-3.3 ± 2.9-4.1 ± 2.1-3.0 ± 2.1
Day 9 predose AM0.6 ± 2.1-4.3 ± 1.5-1.6 ± 1.5
Day 10 predose AM0.1 ± 2.4-3.7 ± 1.7-5.0 ± 1.8
Day 11 predose AM2.2 ± 2.5-6.4 ± 1.8-3.1 ± 1.9
Day 12 predose AM-1.1 ± 2.0-3.5 ± 1.5-5.6 ± 1.5
Day 13 predose AM0.1 ± 2.2-4.8 ± 1.6-4.4 ± 1.6
Day 13 postdose AM: 1 hour-2.0 ± 2.1-11.0 ± 1.6-10.5 ± 1.6
Day 13 postdose AM: 4 hour-2.5 ± 2.9-8.6 ± 2.1-9.0 ± 2.2
Day 13 predose PM0.1 ± 2.7-7.8 ± 2.0-7.0 ± 2.0
Day 14 predose AM-4.4 ± 3.1-6.1 ± 2.3-4.1 ± 2.3
Day 15/Discharge-0.9 ± 2.4-3.5 ± 1.8-1.6 ± 1.8
Day 21/Follow-Up0.1 ± 1.8-0.7 ± 1.30.3 ± 1.3
Day 42/End of Trial0.7 ± 3.32.8 ± 2.41.5 ± 2.4
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.6 · 95% CI -8.9 to 3.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.0 · 95% CI -8.4 to 4.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.9 · 95% CI -9.2 to 3.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -7.1 · 95% CI -13.5 to -0.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.5 · 95% CI -11.5 to 0.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.6 · 95% CI -10.8 to 1.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.6 · 95% CI -9.4 to 2.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.1 · 95% CI -8.0 to 3.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.0 · 95% CI -13.8 to 3.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.7 · 95% CI -11.7 to 6.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.4 · 95% CI -9.7 to 0.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.1 · 95% CI -8.5 to 2.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.7 · 95% CI -13.1 to -0.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.3 · 95% CI -11.8 to 1.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.4 · 95% CI -14.2 to 3.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.5 · 95% CI -17.5 to 0.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.7 · 95% CI -11.6 to 0.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.6 · 95% CI -10.6 to 1.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.5 · 95% CI -7.4 to 6.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.3 · 95% CI -9.3 to 4.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.4 · 95% CI -9.4 to 4.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.5 · 95% CI -8.7 to 5.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.2 · 95% CI -6.2 to 6.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.3 · 95% CI -6.2 to 6.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.5 · 95% CI -6.4 to 9.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.3 · 95% CI -9.3 to 6.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.3 · 95% CI -10.0 to 1.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.5 · 95% CI -10.3 to 1.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.4 · 95% CI -8.2 to 3.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -7.1 · 95% CI -13.0 to -1.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.8 · 95% CI -7.7 to 2.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.7 · 95% CI -9.7 to 0.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.1 · 95% CI -11.6 to 3.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.3 · 95% CI -12.0 to 3.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.3 · 95% CI -10.6 to 1.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.7 · 95% CI -12.0 to 0.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.0 · 95% CI -8.3 to 10.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.2 · 95% CI -9.2 to 9.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.6 · 95% CI -11.5 to 2.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.9 · 95% CI -9.9 to 4.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.3 · 95% CI -15.5 to -3.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.3 · 95% CI -14.6 to -1.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.3 · 95% CI -12.6 to 2.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.3 · 95% CI -8.7 to 6.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.7 · 95% CI -8.2 to 6.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.3 · 95% CI -7.3 to 7.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.9 · 95% CI -10.3 to 0.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.2 · 95% CI -7.7 to 3.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.9 · 95% CI -10.0 to 2.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.1 · 95% CI -11.4 to 1.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.7 · 95% CI -15.2 to -2.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.3 · 95% CI -12.0 to 1.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.4 · 95% CI -7.6 to 2.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.5 · 95% CI -9.7 to 0.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.9 · 95% CI -10.7 to 0.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.6 · 95% CI -10.4 to 1.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.0 · 95% CI -14.6 to -3.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.5 · 95% CI -14.2 to -2.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.2 · 95% CI -13.8 to 1.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.5 · 95% CI -14.3 to 1.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.0 · 95% CI -15.0 to -1.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -7.1 · 95% CI -14.2 to 0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.7 · 95% CI -9.8 to 6.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.3 · 95% CI -8.0 to 8.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.6 · 95% CI -9.0 to 3.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.7 · 95% CI -7.1 to 5.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.8 · 95% CI -5.5 to 3.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.2 · 95% CI -4.6 to 4.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.1 · 95% CI -6.5 to 10.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.8 · 95% CI -7.9 to 9.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Study Baseline Over Time in Supine Pulse
Time frame:
Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Reported as:
Least squares mean · bpm
Change From Study Baseline Over Time in Supine Pulse
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline (Day 1 predose AM)70.3 ± 13.770.3 ± 10.970.0 ± 10.3
Day 1 postdose AM: 1 hour1.0 ± 4.17.2 ± 3.110.2 ± 3.1
Day 1 postdose AM: 4 hour4.3 ± 3.44.3 ± 2.78.8 ± 2.7
Day 1 postdose AM: 8 hour2.8 ± 2.82.6 ± 2.24.5 ± 2.2
Day 1 predose PM0 ± 2.75.1 ± 2.15.3 ± 2.1
Day 1 postdose PM: 1 hour2.3 ± 2.84.6 ± 2.23.7 ± 2.2
Day 2 predose AM-2.6 ± 2.3-1.7 ± 1.8-1.9 ± 1.8
Day 2 postdose AM: 1 hour7.0 ± 4.19.5 ± 3.111.3 ± 3.1
Day 2 postdose AM: 4 hour3.2 ± 3.06.5 ± 2.310.2 ± 2.3
Day 2 predose PM7.9 ± 2.76.5 ± 2.16.6 ± 2.1
Day 2 postdose PM: 1 hour7.2 ± 3.67.3 ± 2.87.0 ± 2.8
Day 2 postdose PM: 4 hour1.9 ± 2.43.0 ± 1.84.8 ± 1.8
Day 3 predose AM0.2 ± 2.3-1.2 ± 1.8-0.2 ± 1.8
Day 3 postdose PM: 4 hour3.0 ± 2.90.7 ± 2.25.2 ± 2.2
Day 4 predose AM-4.1 ± 2.62.8 ± 2.00.9 ± 2.0
Day 5 predose AM-3.3 ± 2.3-0.4 ± 1.8-0.6 ± 1.8
Day 6 predose AM-0.8 ± 2.91.5 ± 2.3-1.5 ± 2.3
Day 7 predose AM-4.0 ± 2.51.1 ± 2.01.0 ± 2.0
Day 7 postdose AM: 1 hour0.2 ± 4.29.5 ± 3.213.2 ± 3.2
Day 7 postdose AM: 4 hour-2.6 ± 2.64.4 ± 2.08.8 ± 2.0
Day 8 predose AM-2.8 ± 2.6-0.9 ± 2.01.3 ± 2.0
Day 8 postdose AM: 1 hour2.7 ± 3.812.4 ± 2.912.3 ± 2.9
Day 8 postdose AM: 4 hour-0.6 ± 3.07.1 ± 2.37.7 ± 2.3
Day 8 predose PM2.7 ± 3.26.0 ± 2.55.7 ± 2.5
Day 9 predose AM-1.8 ± 2.9-0.3 ± 2.30.5 ± 2.3
Day 10 predose AM-3.0 ± 3.21.3 ± 2.42.1 ± 2.4
Day 11 predose AM2.2 ± 3.60.7 ± 2.81.4 ± 2.8
Day 12 predose AM-0.6 ± 4.02.3 ± 3.10.6 ± 3.1
Day 13 predose AM-0.2 ± 3.60.8 ± 2.8-0.1 ± 2.8
Day 13 postdose AM: 1 hour0.3 ± 3.27.3 ± 2.510.2 ± 2.5
Day 13 postdose AM: 4 hour-0.8 ± 2.54.8 ± 2.06.4 ± 2.0
Day 13 predose PM5.0 ± 3.04.5 ± 2.37.0 ± 2.3
Day 14 predose AM-3.1 ± 3.00.7 ± 2.30.1 ± 2.3
Day 15/Discharge1.1 ± 2.90.7 ± 2.31.5 ± 2.3
Day 21/Follow-Up-1.3 ± 4.1-2.0 ± 3.25.4 ± 3.2
Day 42/End of Trial0.4 ± 3.60.6 ± 2.81.2 ± 2.8
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 6.2 · 95% CI -4.4 to 16.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 9.1 · 95% CI -1.5 to 19.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0 · 95% CI -9.0 to 9.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.4 · 95% CI -4.6 to 13.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.2 · 95% CI -7.5 to 7.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.6 · 95% CI -5.7 to 8.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.1 · 95% CI -2.0 to 12.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.2 · 95% CI -1.8 to 12.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.3 · 95% CI -5.1 to 9.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.3 · 95% CI -6.0 to 8.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.0 · 95% CI -5.0 to 6.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.7 · 95% CI -5.3 to 6.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.5 · 95% CI -8.1 to 13.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.3 · 95% CI -6.3 to 15.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.3 · 95% CI -4.6 to 11.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 7.0 · 95% CI -1.0 to 14.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.3 · 95% CI -8.5 to 5.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.3 · 95% CI -8.5 to 5.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.1 · 95% CI -9.2 to 9.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.2 · 95% CI -9.5 to 9.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.2 · 95% CI -5.1 to 7.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.9 · 95% CI -3.4 to 9.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.4 · 95% CI -7.5 to 4.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.4 · 95% CI -6.5 to 5.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.3 · 95% CI -9.9 to 5.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.2 · 95% CI -5.4 to 9.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 7.0 · 95% CI 0.2 to 13.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.0 · 95% CI -1.7 to 11.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.9 · 95% CI -3.1 to 9.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.6 · 95% CI -3.4 to 8.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.3 · 95% CI -5.4 to 10.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.7 · 95% CI -8.4 to 7.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.1 · 95% CI -1.6 to 11.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.0 · 95% CI -1.7 to 11.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 9.3 · 95% CI -1.6 to 20.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 13.0 · 95% CI 2.1 to 23.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 7.1 · 95% CI 0.2 to 13.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 11.5 · 95% CI 4.6 to 18.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.9 · 95% CI -4.8 to 8.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.1 · 95% CI -2.6 to 10.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 9.7 · 95% CI -0.1 to 19.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 9.6 · 95% CI -0.3 to 19.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 7.8 · 95% CI 0 to 15.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 8.3 · 95% CI 0.6 to 16.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.3 · 95% CI -5.1 to 11.7Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.0 · 95% CI -5.4 to 11.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.5 · 95% CI -6.1 to 9.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.3 · 95% CI -5.3 to 9.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.3 · 95% CI -4.0 to 12.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.1 · 95% CI -3.2 to 13.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.5 · 95% CI -11.0 to 8.0Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.9 · 95% CI -10.3 to 8.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.9 · 95% CI -7.7 to 13.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.2 · 95% CI -9.4 to 11.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.0 · 95% CI -8.4 to 10.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.1 · 95% CI -9.3 to 9.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 7.0 · 95% CI -1.3 to 15.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 9.9 · 95% CI 1.6 to 18.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.6 · 95% CI -1.0 to 12.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 7.2 · 95% CI 0.5 to 13.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.5 · 95% CI -8.4 to 7.4Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.9 · 95% CI -6.0 to 9.9Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.9 · 95% CI -4.0 to 11.8Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.3 · 95% CI -4.6 to 11.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.3 · 95% CI -8.0 to 7.3Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.5 · 95% CI -7.2 to 8.1Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.7 · 95% CI -11.5 to 10.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 6.7 · 95% CI -4.1 to 17.5Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.3 · 95% CI -9.1 to 9.6Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.8 · 95% CI -8.5 to 10.2Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryPercentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Time frame:
Baseline, Days 1-14, Day 15, 21, 42
Reported as:
Number · percentage of participants
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
percentage of participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Baseline33.380.060.0
Day 1100100100
Day 266.7100100
Day 366.710090.0
Day 450.010090.0
Day 550.070.090.0
Day 666.790.090.0
Day 750.090.090.0
Day 883.390.0100
Day 933.310070.0
Day 1033.310070.0
Day 1150.010070.0
Day 1250.090.080.0
Day 1366.7100100
Day 1450.090.080.0
Day 15 / Discharge33.310070.0
Day 21 / Follow-Up50.080.050.0
Day 42 / End of Trial33.340.060.0
PrimaryOrthostatic Systolic Blood Pressure Over Time

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

Time frame:
Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Reported as:
Mean · mmHg
Orthostatic Systolic Blood Pressure Over Time
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Day -1, 1 hour AM-0.8 ± 11.92.0 ± 12.15.6 ± 11.5
Day -1, 4 hour AM0.3 ± 6.42.9 ± 9.92.3 ± 11.5
Day -1, 0 hour PM3.0 ± 10.51.7 ± 12.4-0.1 ± 7.3
Day -1, 1 hour PM3.8 ± 9.05.3 ± 13.83.1 ± 11.5
Day 1, 0 hour AM1.3 ± 9.65.2 ± 11.83.7 ± 12.7
Day 1, 1 hour AM9.7 ± 7.93.7 ± 15.82.5 ± 11.5
Day 1, 4 hour AM3.0 ± 14.612.1 ± 11.35.8 ± 8.3
Day 1, 8 hour AM5.3 ± 6.44.7 ± 12.45.1 ± 11.5
Day 1, 0 hour PM10.2 ± 10.54.1 ± 17.00.2 ± 10.3
Day 1, 1 hour PM5.7 ± 10.20.7 ± 18.04.1 ± 11.4
Day 1, 4 hour PM4.3 ± 14.40.4 ± 14.86.4 ± 5.3
Day 2, 0 hour AM-2.7 ± 11.02.5 ± 13.51.1 ± 10.3
Day 2, 1 hour AM-4.7 ± 15.02.9 ± 8.52.2 ± 8.6
Day 2, 4 hour AM-1.7 ± 11.45.8 ± 6.84.6 ± 10.6
Day 2, 0 Hour PM-6.0 ± 14.96.6 ± 11.92.3 ± 10.4
Day 2, 1 hour PM2.7 ± 14.45.0 ± 14.30.5 ± 14.0
Day 2, 4 hour PM0.8 ± 6.8-0.7 ± 18.97.1 ± 13.1
Day 7, 0 hour AM1.0 ± 7.62.5 ± 19.14.9 ± 10.7
Day 7, 1 hour AM-2.0 ± 6.86.3 ± 11.7-2.5 ± 8.0
Day 7, 4 hour AM-1.2 ± 10.84.7 ± 11.34.7 ± 14.1
Day 8, 0 hour AM-4.0 ± 13.76.5 ± 11.9-1.1 ± 5.7
Day 8, 1 hour AM-2.5 ± 8.55.9 ± 14.71.7 ± 12.6
Day 8, 4 hour AM1.0 ± 12.32.9 ± 10.3-1.7 ± 16.0
Day 8, 0 hour PM1.0 ± 8.45.0 ± 9.74.2 ± 8.8
Day 13, 0 hour AM-2.0 ± 5.26.2 ± 13.71.3 ± 7.4
Day 13, 1 hour AM-1.5 ± 12.88.3 ± 13.71.4 ± 12.1
Day 13, 4 hour AM0.8 ± 7.44.1 ± 10.92.2 ± 11.7
Day 13, 0 hour PM3.8 ± 9.14.8 ± 14.23.2 ± 10.3
PrimaryOrthostatic Diastolic Blood Pressure Over Time

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

Time frame:
Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Reported as:
Mean · mmHg
Orthostatic Diastolic Blood Pressure Over Time
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Day -1, 1 hour AM1.8 ± 3.03.3 ± 6.86.3 ± 5.9
Day -1, 4 hour AM-0.5 ± 5.13.6 ± 8.25.5 ± 6.4
Day -1, 0 hour PM8.2 ± 4.64.2 ± 5.63.4 ± 4.4
Day -1, 1 hour PM5.7 ± 4.64.0 ± 6.84.5 ± 4.3
Day 1, 0 hour AM3.3 ± 5.24.2 ± 4.45.4 ± 4.6
Day 1, 1 hour AM5.3 ± 8.92.9 ± 5.13.4 ± 5.9
Day 1, 4 hour AM4.2 ± 4.16.1 ± 5.87.0 ± 5.0
Day 1, 8 hour AM5.3 ± 1.93.6 ± 4.54.9 ± 6.0
Day 1, 0 hour PM10.0 ± 6.82.8 ± 6.35.1 ± 6.2
Day 1, 1 hour PM3.0 ± 4.35.2 ± 9.25.1 ± 4.3
Day 1, 4 hour PM6.8 ± 4.23.4 ± 7.37.7 ± 4.9
Day 2, 0 hour AM2.7 ± 2.03.3 ± 5.23.3 ± 6.0
Day 2, 1 hour AM3.0 ± 4.11.8 ± 5.85.2 ± 3.2
Day 2, 4 hour AM0.5 ± 2.43.8 ± 3.55.7 ± 5.3
Day 2, 0 Hour PM-2.7 ± 10.23.2 ± 7.44.7 ± 5.2
Day 2, 1 hour PM2.3 ± 5.60.9 ± 6.15.3 ± 5.1
Day 2, 4 hour PM5.8 ± 4.31.3 ± 10.08.7 ± 7.5
Day 7, 0 hour AM2.3 ± 3.42.9 ± 7.95.6 ± 6.2
Day 7, 1 hour AM1.8 ± 2.93.7 ± 5.52.4 ± 3.5
Day 7, 4 hour AM7.3 ± 9.04.8 ± 7.43.2 ± 6.5
Day 8, 0 hour AM3.3 ± 6.16.2 ± 7.14.8 ± 5.5
Day 8, 1 hour AM-1.3 ± 8.92.2 ± 8.43.8 ± 6.7
Day 8, 4 hour AM4.0 ± 2.61.9 ± 7.31.2 ± 7.3
Day 8, 0 hour PM5.0 ± 2.63.8 ± 4.54.2 ± 4.0
Day 13, 0 hour AM2.7 ± 5.14.0 ± 6.83.9 ± 4.1
Day 13, 1 hour AM3.3 ± 4.35.8 ± 4.75.0 ± 7.1
Day 13, 4 hour AM0.7 ± 4.53.7 ± 4.35.4 ± 7.7
Day 13, 0 hour PM4.0 ± 3.25.1 ± 6.33.9 ± 3.8
PrimaryOrthostatic Pulse Over Time

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

Time frame:
Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Reported as:
Mean · bpm
Orthostatic Pulse Over Time
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Day -1, 1 hour AM9.2 ± 6.49.2 ± 4.310.2 ± 8.8
Day -1, 4 hour AM4.7 ± 9.810.9 ± 5.89.5 ± 8.3
Day -1, 0 hour PM15.3 ± 15.010.1 ± 4.79.8 ± 4.9
Day -1, 1 hour PM11.3 ± 3.911.0 ± 4.311.4 ± 6.0
Day 1, 0 hour AM4.8 ± 10.48.8 ± 4.310.3 ± 7.7
Day 1, 1 hour AM8.7 ± 6.69.7 ± 5.912.9 ± 6.9
Day 1, 4 hour AM7.7 ± 7.411.0 ± 6.110.1 ± 8.4
Day 1, 8 hour AM10.0 ± 4.79.9 ± 6.310.5 ± 4.6
Day 1, 0 hour PM14.8 ± 9.99.1 ± 6.67.7 ± 4.1
Day 1, 1 hour PM9.3 ± 6.210.8 ± 7.211.1 ± 6.6
Day 1, 4 hour PM16.5 ± 12.714.5 ± 7.216.5 ± 10.0
Day 2, 0 hour AM9.0 ± 3.010.4 ± 7.010.5 ± 4.7
Day 2, 1 hour AM6.5 ± 6.011.2 ± 8.710.7 ± 5.8
Day 2, 4 hour AM11.2 ± 9.28.4 ± 6.58.8 ± 6.2
Day 2, 0 Hour PM6.0 ± 8.68.6 ± 5.89.0 ± 4.2
Day 2, 1 hour PM10.0 ± 5.49.4 ± 6.87.9 ± 4.6
Day 2, 4 hour PM10.8 ± 6.315.9 ± 8.613.6 ± 7.1
Day 7, 0 hour AM10.8 ± 5.27.1 ± 8.59.7 ± 4.6
Day 7, 1 hour AM11.5 ± 6.39.5 ± 6.610.1 ± 7.9
Day 7, 4 hour AM10.8 ± 3.38.7 ± 2.69.6 ± 4.7
Day 8, 0 hour AM10.3 ± 8.38.6 ± 8.69.5 ± 7.8
Day 8, 1 hour AM5.3 ± 9.39.5 ± 8.710.5 ± 3.3
Day 8, 4 hour AM10.7 ± 7.48.1 ± 7.87.3 ± 6.1
Day 8, 0 hour PM9.3 ± 3.69.6 ± 5.68.9 ± 4.7
Day 13, 0 hour AM7.8 ± 14.99.1 ± 8.610.9 ± 5.9
Day 13, 1 hour AM11.0 ± 4.67.9 ± 6.011.2 ± 7.5
Day 13, 4 hour AM14.5 ± 8.19.1 ± 6.011.5 ± 5.9
Day 13, 0 hour PM9.3 ± 3.49.3 ± 4.611.2 ± 4.3
PrimaryChange From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure

24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Time Matched Baseline (Day -1)132.34 ± 8.22126.40 ± 11.07129.00 ± 6.48127.70 ± 8.93
Change at Day 1-0.60 ± 2.39-3.92 ± 1.84-3.15 ± 1.81-3.53 ± 1.29
Change at Day 7-3.54 ± 2.68-6.77 ± 2.07-3.03 ± 2.04-4.90 ± 1.45
Change at Day 14-4.87 ± 3.17-7.58 ± 2.59-6.74 ± 2.39-7.16 ± 1.75
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.32 · 95% CI -9.68 to 3.04Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.55 · 95% CI -8.76 to 3.66Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -2.93 · 95% CI -8.62 to 2.75Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.23 · 95% CI -10.37 to 3.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.52 · 95% CI -6.46 to 7.49Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -1.36 · 95% CI -7.74 to 5.03Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.71 · 95% CI -11.46 to 6.04Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.87 · 95% CI -10.09 to 6.35Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -2.29 · 95% CI -9.93 to 5.35Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure

Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)136.99 ± 8.42130.64 ± 10.82132.28 ± 7.07
Change at Day 1-0.74 ± 2.81-7.80 ± 2.14-4.93 ± 2.12
Change at Day 7-5.27 ± 2.89-9.09 ± 2.20-3.85 ± 2.17
Change at Day 14-6.37 ± 3.62-12.81 ± 2.92-7.40 ± 2.71
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.06 · 95% CI -14.52 to 0.40Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.19 · 95% CI -11.52 to 3.14Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.82 · 95% CI -11.47 to 3.83Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.42 · 95% CI -6.10 to 8.94Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.44 · 95% CI -16.36 to 3.47Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.03 · 95% CI -10.44 to 8.38Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure

Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)126.76 ± 9.36121.77 ± 12.26125.26 ± 7.24
Change at Day 10.11 ± 2.55-0.11 ± 1.98-1.50 ± 1.96
Change at Day 7-1.42 ± 2.93-4.54 ± 2.28-2.25 ± 2.25
Change at Day 14-3.25 ± 3.17-2.38 ± 2.63-6.23 ± 2.44
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.22 · 95% CI -6.97 to 6.54Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.60 · 95% CI -8.24 to 5.03Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.12 · 95% CI -10.88 to 4.65Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.82 · 95% CI -8.45 to 6.80Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.87 · 95% CI -7.84 to 9.58Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.98 · 95% CI -11.23 to 5.26Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure

Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

Time frame:
Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time-matched baseline (Day -1): 0-4 hours134.45 ± 8.01128.18 ± 9.90128.38 ± 7.33
Time-matched baseline (Day -1): 4-8 hours136.10 ± 9.69130.04 ± 13.15132.53 ± 6.83
Time-matched baseline (Day -1): 8-12 hours140.46 ± 9.12133.67 ± 11.90135.93 ± 8.51
Time-matched baseline (Day -1): 12-16 hours130.31 ± 9.75124.00 ± 11.93128.44 ± 11.32
Time-matched baseline (Day -1): 16-20 hours120.34 ± 8.79119.75 ± 14.51120.41 ± 11.00
Time-matched baseline (Day -1): 20-24 hours132.10 ± 11.62122.77 ± 9.60128.13 ± 7.19
Day 1, 0-4 hours-1.61 ± 3.02-7.15 ± 2.27-4.08 ± 2.27
Day 1, 4-8 hours-0.62 ± 3.51-8.67 ± 2.70-8.89 ± 2.67
Day 1, 8-12 hours1.21 ± 3.80-8.14 ± 2.91-1.84 ± 2.88
Day 1, 12-16 hours-4.83 ± 3.04-1.46 ± 2.37-2.00 ± 2.34
Day 1, 16-20 hours3.77 ± 4.12-0.66 ± 3.19-1.08 ± 3.19
Day 1, 20-24 hours2.08 ± 3.041.27 ± 2.37-0.55 ± 2.27
Day 7, 0-4 hours-5.14 ± 3.14-10.68 ± 2.35-5.15 ± 2.35
Day 7, 4-8 hours-6.24 ± 3.44-9.13 ± 2.65-4.07 ± 2.62
Day 7, 8-12 hours-3.70 ± 3.65-7.93 ± 2.80-2.33 ± 2.76
Day 7, 12-16 hours-4.46 ± 3.66-5.03 ± 2.86-1.97 ± 2.82
Day 7, 16-20 hours2.75 ± 3.98-5.14 ± 3.08-3.74 ± 3.08
Day 7, 20-24 hours-1.10 ± 3.74-4.94 ± 2.91-0.33 ± 2.80
Day 14, 0-4 hours-6.67 ± 3.92-13.80 ± 3.10-5.01 ± 2.90
Day 14, 4-8 hours-7.36 ± 3.62-13.67 ± 2.95-8.53 ± 2.75
Day 14, 8-12 hours-4.42 ± 4.41-11.43 ± 3.58-8.53 ± 3.31
Day 14, 12-16 hours-5.28 ± 4.14-3.52 ± 3.43-8.75 ± 3.18
Day 14, 16-20 hours-1.06 ± 3.53-2.79 ± 2.89-6.61 ± 2.74
Day 14, 20-24 hours-2.98 ± 3.82-1.00 ± 3.17-1.91 ± 2.84
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.55 · 95% CI -13.51 to 2.41Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.47 · 95% CI -10.41 to 5.47Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.05 · 95% CI -17.36 to 1.25Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.28 · 95% CI -17.42 to 0.87Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.34 · 95% CI -19.43 to 0.74Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.05 · 95% CI -12.95 to 6.84Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.36 · 95% CI -4.74 to 11.47Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.82 · 95% CI -5.10 to 10.75Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.43 · 95% CI -15.23 to 6.37Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.85 · 95% CI -15.65 to 5.94Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.81 · 95% CI -9.10 to 7.47Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.63 · 95% CI -10.42 to 5.16Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.54 · 95% CI -13.80 to 2.72Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.01 · 95% CI -8.25 to 8.23Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.89 · 95% CI -12.01 to 6.23Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.17 · 95% CI -6.78 to 11.13Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.23 · 95% CI -13.93 to 5.47Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.37 · 95% CI -8.14 to 10.88Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.57 · 95% CI -10.32 to 9.18Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.49 · 95% CI -7.04 to 12.02Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.89 · 95% CI -18.33 to 2.55Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.49 · 95% CI -16.92 to 3.95Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.84 · 95% CI -14.03 to 6.35Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.78 · 95% CI -8.80 to 10.35Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.13 · 95% CI -17.79 to 3.53Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.66 · 95% CI -8.59 to 11.91Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.31 · 95% CI -16.17 to 3.55Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.17 · 95% CI -10.60 to 8.27Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.01 · 95% CI -19.13 to 5.11Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.11 · 95% CI -15.55 to 7.34Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.77 · 95% CI -9.63 to 13.17Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.47 · 95% CI -14.25 to 7.31Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.73 · 95% CI -11.24 to 7.77Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.55 · 95% CI -14.83 to 3.73Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.98 · 95% CI -8.85 to 12.81Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.07 · 95% CI -8.68 to 10.82Least squares mean difference and associated 95% CI are from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure

24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Time Matched Baseline (Day -1)96.44 ± 8.3890.27 ± 6.8991.14 ± 5.5490.71 ± 6.10
Change at Day 1-0.68 ± 1.61-2.80 ± 1.20-3.07 ± 1.19-2.94 ± 0.85
Change at Day 7-1.84 ± 1.83-5.24 ± 1.37-3.46 ± 1.35-4.35 ± 0.97
Change at Day 14-1.55 ± 2.28-6.50 ± 1.79-6.05 ± 1.65-6.28 ± 1.23
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.12 · 95% CI -6.38 to 2.15Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.39 · 95% CI -6.59 to 1.80Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -2.26 · 95% CI -6.11 to 1.60Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.39 · 95% CI -8.25 to 1.47Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.61 · 95% CI -6.40 to 3.18Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -2.50 · 95% CI -6.90 to 1.90Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.96 · 95% CI -11.22 to 1.31Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.50 · 95% CI -10.41 to 1.40Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -4.73 · 95% CI -10.27 to 0.81Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure

Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)100.09 ± 7.1493.31 ± 7.3694.00 ± 5.54
Change at Day 1-0.20 ± 2.24-5.07 ± 1.65-5.22 ± 1.63
Change at Day 7-2.60 ± 2.01-6.82 ± 1.48-4.75 ± 1.46
Change at Day 14-1.97 ± 2.50-10.71 ± 1.94-7.31 ± 1.79
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.87 · 95% CI -10.80 to 1.06Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.02 · 95% CI -10.87 to 0.83Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.23 · 95% CI -9.55 to 1.10Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.15 · 95% CI -7.40 to 3.11Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.74 · 95% CI -15.64 to -1.85Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.34 · 95% CI -11.84 to 1.15Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure

Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)91.93 ± 10.0386.85 ± 7.5787.77 ± 6.37
Change at Day 1-0.39 ± 1.67-0.84 ± 1.27-1.10 ± 1.26
Change at Day 7-0.47 ± 2.07-3.79 ± 1.57-2.20 ± 1.56
Change at Day 14-0.54 ± 2.46-2.42 ± 1.97-4.83 ± 1.84
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.45 · 95% CI -4.86 to 3.96Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.71 · 95% CI -5.07 to 3.65Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.32 · 95% CI -8.79 to 2.14Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.74 · 95% CI -7.14 to 3.67Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.88 · 95% CI -8.58 to 4.83Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.30 · 95% CI -10.69 to 2.10Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure

Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

Time frame:
Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time-matched baseline (Day -1): 0-4 hours98.10 ± 5.1091.52 ± 7.0091.16 ± 4.64
Time-matched baseline (Day -1): 4-8 hours98.92 ± 8.6492.27 ± 7.7393.98 ± 4.94
Time-matched baseline (Day -1): 8-12 hours103.25 ± 8.6696.20 ± 9.5096.76 ± 8.22
Time-matched baseline (Day -1): 12-16 hours93.31 ± 9.8287.07 ± 6.7590.02 ± 8.80
Time-matched baseline (Day -1): 16-20 hours87.48 ± 10.4285.54 ± 9.6883.70 ± 9.24
Time-matched baseline (Day -1): 20-24 hours97.62 ± 11.4889.30 ± 6.4090.96 ± 6.46
Day 1, 0-4 hours-0.40 ± 2.61-4.84 ± 1.86-5.57 ± 1.88
Day 1, 4-8 hours0.24 ± 2.86-4.98 ± 2.15-7.97 ± 2.11
Day 1, 8-12 hours0.84 ± 2.87-5.87 ± 2.15-2.30 ± 2.14
Day 1, 12-16 hours-2.21 ± 1.90-1.84 ± 1.47-2.23 ± 1.44
Day 1, 16-20 hours1.47 ± 2.96-0.86 ± 2.28-0.97 ± 2.29
Day 1, 20-24 hours0.99 ± 2.200.25 ± 1.63-0.13 ± 1.60
Day 7, 0-4 hours-2.77 ± 2.13-7.90 ± 1.52-6.41 ± 1.53
Day 7, 4-8 hours-2.54 ± 2.73-6.46 ± 2.06-4.99 ± 2.02
Day 7, 8-12 hours-1.71 ± 2.33-6.47 ± 1.74-2.96 ± 1.73
Day 7, 12-16 hours-2.35 ± 2.42-4.46 ± 1.86-2.30 ± 1.83
Day 7, 16-20 hours2.93 ± 2.89-3.73 ± 2.23-3.45 ± 2.24
Day 7, 20-24 hours-1.18 ± 2.62-3.47 ± 1.94-1.35 ± 1.91
Day 14, 0-4 hours-2.65 ± 2.67-10.39 ± 1.99-6.51 ± 1.86
Day 14, 4-8 hours-2.26 ± 2.38-11.78 ± 1.89-7.91 ± 1.74
Day 14, 8-12 hours-1.27 ± 3.35-9.89 ± 2.65-7.32 ± 2.46
Day 14, 12-16 hours-1.55 ± 3.31-2.91 ± 2.71-6.50 ± 2.49
Day 14, 16-20 hours0.05 ± 2.75-3.38 ± 2.23-5.33 ± 2.12
Day 14, 20-24 hours-0.49 ± 2.70-0.57 ± 2.12-2.38 ± 1.95
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.45 · 95% CI -11.30 to 2.41Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.17 · 95% CI -12.10 to 1.75Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.23 · 95% CI -12.87 to 2.42Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -8.22 · 95% CI -15.64 to -0.79Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.72 · 95% CI -14.29 to 0.86Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.14 · 95% CI -10.66 to 4.38Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.37 · 95% CI -4.71 to 5.45Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.02 · 95% CI -4.94 to 4.91Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.33 · 95% CI -10.07 to 5.41Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.45 · 95% CI -10.26 to 5.37Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.75 · 95% CI -6.62 to 5.13Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.13 · 95% CI -6.83 to 4.58Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.13 · 95% CI -10.72 to 0.47Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.64 · 95% CI -9.29 to 2.01Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.92 · 95% CI -11.22 to 3.38Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.46 · 95% CI -9.54 to 4.63Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.75 · 95% CI -10.90 to 1.39Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.25 · 95% CI -7.35 to 4.85Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.11 · 95% CI -8.57 to 4.35Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.05 · 95% CI -6.21 to 6.31Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.66 · 95% CI -14.22 to 0.90Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.38 · 95% CI -14.01 to 1.25Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.29 · 95% CI -9.30 to 4.71Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.17 · 95% CI -6.97 to 6.64Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.74 · 95% CI -15.03 to -0.44Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.86 · 95% CI -10.88 to 3.16Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -9.53 · 95% CI -16.10 to -2.95Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.66 · 95% CI -11.82 to 0.50Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.62 · 95% CI -17.77 to 0.54Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.05 · 95% CI -14.79 to 2.69Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.36 · 95% CI -10.51 to 7.79Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.95 · 95% CI -13.50 to 3.60Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.43 · 95% CI -10.81 to 3.96Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.38 · 95% CI -12.64 to 1.89Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.08 · 95% CI -7.55 to 7.39Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.89 · 95% CI -8.89 to 5.12Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure

24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Time Matched Baseline (Day -1)77.37 ± 9.2671.57 ± 8.5871.50 ± 6.3371.53 ± 7.34
Change at Day 1-1.73 ± 1.29-2.53 ± 0.96-2.82 ± 0.96-2.67 ± 0.69
Change at Day 7-1.60 ± 1.49-4.27 ± 1.12-3.44 ± 1.12-3.86 ± 0.80
Change at Day 14-1.36 ± 2.04-5.33 ± 1.61-5.53 ± 1.51-5.43 ± 1.11
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.79 · 95% CI -4.17 to 2.59Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.09 · 95% CI -4.47 to 2.29Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -0.94 · 95% CI -4.02 to 2.14Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.67 · 95% CI -6.60 to 1.26Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.84 · 95% CI -5.77 to 2.10Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -2.25 · 95% CI -5.83 to 1.32Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.97 · 95% CI -9.50 to 1.56Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.17 · 95% CI -9.52 to 1.18Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -4.07 · 95% CI -9.01 to 0.87Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure

Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)80.71 ± 8.6574.31 ± 9.1974.20 ± 6.45
Change at Day 1-0.88 ± 1.76-4.28 ± 1.31-4.47 ± 1.31
Change at Day 7-2.36 ± 1.61-5.66 ± 1.20-4.36 ± 1.20
Change at Day 14-1.59 ± 2.03-8.88 ± 1.59-6.69 ± 1.50
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.40 · 95% CI -8.01 to 1.21Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.60 · 95% CI -8.21 to 1.02Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.30 · 95% CI -7.53 to 0.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.01 · 95% CI -6.24 to 2.23Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.29 · 95% CI -12.80 to -1.79Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.10 · 95% CI -10.43 to 0.23Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure

Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)73.42 ± 10.0468.44 ± 8.6068.36 ± 6.80
Change at Day 1-2.02 ± 1.51-1.03 ± 1.14-1.46 ± 1.14
Change at Day 7-0.42 ± 1.94-2.96 ± 1.47-2.68 ± 1.47
Change at Day 14-0.81 ± 2.41-1.84 ± 1.92-4.48 ± 1.81
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.99 · 95% CI -2.97 to 4.95Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.55 · 95% CI -3.41 to 4.52Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.54 · 95% CI -7.63 to 2.56Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.26 · 95% CI -7.36 to 2.85Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.03 · 95% CI -7.55 to 5.49Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -3.68 · 95% CI -10.00 to 2.65Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure

Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

Time frame:
Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Reported as:
Least squares mean · mmHg
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
mmHgPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1): 0-4 hours78.96 ± 8.7072.48 ± 8.5871.58 ± 5.46
Time Matched Baseline (Day -1): 4-8 hours79.85 ± 9.3473.96 ± 8.8573.79 ± 6.71
Time Matched Baseline (Day -1): 8-12 hours83.31 ± 8.4976.47 ± 11.7677.13 ± 8.49
Time Matched Baseline (Day -1): 12-16 hours74.27 ± 10.8868.10 ± 7.9270.29 ± 8.87
Time Matched Baseline (Day -1): 16-20 hours70.07 ± 9.1667.89 ± 10.0464.87 ± 8.26
Time Matched Baseline (Day -1): 20-24 hours77.61 ± 10.9570.57 ± 8.3571.04 ± 7.34
Day 1, 0-4 hours-0.57 ± 1.98-3.15 ± 1.45-4.63 ± 1.47
Day 1, 4-8 hours-1.02 ± 2.15-4.88 ± 1.61-5.75 ± 1.61
Day 1, 8-12 hours-0.08 ± 2.64-5.18 ± 1.99-3.04 ± 1.99
Day 1, 12-16 hours-2.99 ± 2.10-2.12 ± 1.61-2.44 ± 1.59
Day 1, 16-20 hours-1.41 ± 2.56-1.97 ± 1.96-1.87 ± 1.99
Day 1, 20-24 hours-0.13 ± 1.891.59 ± 1.410.12 ± 1.40
Day 7, 0-4 hours-1.88 ± 1.56-6.31 ± 1.14-6.05 ± 1.15
Day 7, 4-8 hours-2.55 ± 2.45-5.94 ± 1.83-3.61 ± 1.84
Day 7, 8-12 hours-2.16 ± 2.01-4.98 ± 1.52-3.52 ± 1.51
Day 7, 12-16 hours-2.18 ± 2.32-3.37 ± 1.78-3.45 ± 1.75
Day 7, 16-20 hours2.29 ± 2.62-3.57 ± 2.01-3.91 ± 2.03
Day 7, 20-24 hours-0.13 ± 2.37-1.74 ± 1.77-0.76 ± 1.76
Day 14, 0-4 hours-2.02 ± 2.16-8.92 ± 1.66-6.06 ± 1.57
Day 14, 4-8 hours-1.52 ± 1.98-9.77 ± 1.56-7.07 ± 1.47
Day 14, 8-12 hours-0.98 ± 2.99-8.06 ± 2.39-6.83 ± 2.24
Day 14, 12-16 hours-0.91 ± 3.19-2.32 ± 2.59-6.07 ± 2.40
Day 14, 16-20 hours-0.94 ± 2.91-3.30 ± 2.34-5.44 ± 2.24
Day 14, 20-24 hours0.50 ± 2.640.06 ± 2.08-1.48 ± 1.95
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.58 · 95% CI -7.76 to 2.59Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.06 · 95% CI -9.32 to 1.19Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.86 · 95% CI -9.51 to 1.80Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.73 · 95% CI -10.40 to 0.93Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.10 · 95% CI -12.06 to 1.86Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -2.96 · 95% CI -9.87 to 3.96Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 0.87 · 95% CI -4.70 to 6.45Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.55 · 95% CI -4.90 to 6.01Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.56 · 95% CI -7.22 to 6.10Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.47 · 95% CI -7.27 to 6.34Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.72 · 95% CI -3.26 to 6.69Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.25 · 95% CI -4.69 to 5.20Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -4.43 · 95% CI -8.50 to -0.36Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.17 · 95% CI -8.30 to -0.03Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -3.39 · 95% CI -9.82 to 3.04Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.06 · 95% CI -7.51 to 5.38Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.82 · 95% CI -8.12 to 2.48Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.36 · 95% CI -6.63 to 3.91Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.19 · 95% CI -7.35 to 4.97Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.26 · 95% CI -7.30 to 4.77Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -5.86 · 95% CI -12.68 to 0.95Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -6.20 · 95% CI -13.16 to 0.76Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.61 · 95% CI -7.87 to 4.65Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.63 · 95% CI -6.85 to 5.59Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -6.91 · 95% CI -12.74 to -1.08Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.04 · 95% CI -9.73 to 1.66Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -8.25 · 95% CI -13.59 to -2.91Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.56 · 95% CI -10.76 to -0.35Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -7.07 · 95% CI -15.20 to 1.05Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.85 · 95% CI -13.68 to 1.98Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -1.40 · 95% CI -10.14 to 7.33Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -5.16 · 95% CI -13.46 to 3.14Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -2.37 · 95% CI -10.14 to 5.40Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -4.51 · 95% CI -12.25 to 3.23Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.44 · 95% CI -7.60 to 6.72Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.98 · 95% CI -8.88 to 4.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse

24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · bpm
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Time Matched Baseline (Day -1)75.08 ± 14.0972.81 ± 10.7975.40 ± 10.8474.10 ± 10.61
Change at Day 1-0.90 ± 1.252.29 ± 0.972.64 ± 0.972.47 ± 0.69
Change at Day 7-1.92 ± 1.382.67 ± 1.082.57 ± 1.072.62 ± 0.76
Change at Day 14-0.45 ± 1.502.12 ± 1.232.71 ± 1.162.42 ± 0.84
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.19 · 95% CI -0.10 to 6.48Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.53 · 95% CI 0.25 to 6.82Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: 3.36 · 95% CI 0.40 to 6.32Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.59 · 95% CI 0.95 to 8.23Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.49 · 95% CI 0.86 to 8.12Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: 4.54 · 95% CI 1.27 to 7.81Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.58 · 95% CI -1.45 to 6.61Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.17 · 95% CI -0.78 to 7.11Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: 2.87 · 95% CI -0.71 to 6.45Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse

Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · bpm
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)76.81 ± 15.0075.98 ± 12.8478.18 ± 11.47
Change at Day 10.14 ± 1.842.30 ± 1.424.23 ± 1.43
Change at Day 7-1.80 ± 1.512.75 ± 1.172.22 ± 1.17
Change at Day 14-0.46 ± 1.592.66 ± 1.303.28 ± 1.23
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 2.17 · 95% CI -2.65 to 6.99Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.09 · 95% CI -0.73 to 8.91Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.56 · 95% CI 0.60 to 8.51Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.02 · 95% CI 0.07 to 7.98Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.12 · 95% CI -1.15 to 7.39Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.74 · 95% CI -0.44 to 7.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse

Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.

Time frame:
Time Matched Baseline (Day -1), Days 1, 7, and 14
Reported as:
Least squares mean · bpm
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1)73.43 ± 13.3969.62 ± 8.9172.54 ± 10.46
Change at Day 1-2.01 ± 1.212.29 ± 0.940.93 ± 0.94
Change at Day 7-2.24 ± 1.632.57 ± 1.272.86 ± 1.26
Change at Day 14-0.40 ± 1.791.48 ± 1.462.15 ± 1.38
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.30 · 95% CI 1.10 to 7.49Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.94 · 95% CI -0.23 to 6.10Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.80 · 95% CI 0.50 to 9.11Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.10 · 95% CI 0.84 to 9.36Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.89 · 95% CI -2.93 to 6.70Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.55 · 95% CI -2.15 to 7.25Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse

Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.

Time frame:
Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Reported as:
Least squares mean · bpm
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
bpmPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Time Matched Baseline (Day -1): 0-4 hours73.52 ± 14.0273.89 ± 12.2376.46 ± 9.48
Time Matched Baseline (Day -1): 4-8 hours77.65 ± 15.5776.88 ± 15.0979.91 ± 14.33
Time Matched Baseline (Day -1): 8-12 hours79.00 ± 15.5077.34 ± 11.4278.21 ± 11.67
Time Matched Baseline (Day -1): 12-16 hours78.60 ± 15.2272.93 ± 9.3875.36 ± 11.89
Time Matched Baseline (Day -1): 16-20 hours72.08 ± 13.3767.79 ± 8.8070.51 ± 10.23
Time Matched Baseline (Day -1): 20-24 hours68.05 ± 11.2667.97 ± 8.7571.45 ± 10.35
Day 1, 0-4 hours0.87 ± 2.077.68 ± 1.607.42 ± 1.60
Day 1, 4-8 hours1.18 ± 2.760.23 ± 2.143.02 ± 2.14
Day 1, 8-12 hours-0.96 ± 2.14-1.33 ± 1.652.15 ± 1.65
Day 1, 12-16 hours-4.33 ± 1.682.13 ± 1.301.24 ± 1.29
Day 1, 16-20 hours-1.67 ± 1.241.95 ± 0.970.73 ± 0.96
Day 1, 20-24 hours0.76 ± 1.772.50 ± 1.371.09 ± 1.38
Day 7, 0-4 hours-0.09 ± 2.114.27 ± 1.635.32 ± 1.64
Day 7, 4-8 hours-2.94 ± 1.721.95 ± 1.341.36 ± 1.34
Day 7, 8-12 hours-2.25 ± 1.781.79 ± 1.380.01 ± 1.38
Day 7, 12-16 hours-4.05 ± 1.892.85 ± 1.462.10 ± 1.45
Day 7, 16-20 hours-2.56 ± 1.872.44 ± 1.452.78 ± 1.44
Day 7, 20-24 hours0.23 ± 1.851.91 ± 1.444.26 ± 1.44
Day 14, 0-4 hours0.77 ± 1.954.82 ± 1.594.53 ± 1.51
Day 14, 4-8 hours-2.85 ± 2.562.33 ± 2.092.76 ± 1.99
Day 14, 8-12 hours0.89 ± 1.910.68 ± 1.562.50 ± 1.48
Day 14, 12-16 hours-3.74 ± 2.331.35 ± 1.891.56 ± 1.79
Day 14, 16-20 hours-0.88 ± 1.980.43 ± 1.612.06 ± 1.53
Day 14, 20-24 hours4.14 ± 2.312.80 ± 1.883.00 ± 1.80
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 6.81 · 95% CI 1.40 to 12.22Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 6.55 · 95% CI 1.12 to 11.99Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.95 · 95% CI -8.18 to 6.28Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.85 · 95% CI -5.39 to 9.09Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.38 · 95% CI -5.98 to 5.23Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.10 · 95% CI -2.50 to 8.70Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 6.46 · 95% CI 2.02 to 10.89Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.57 · 95% CI 1.19 to 9.95Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 3.63 · 95% CI 0.34 to 6.91Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.41 · 95% CI -0.84 to 5.66Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.74 · 95% CI -2.89 to 6.36Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 0.33 · 95% CI -4.33 to 4.99Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.36 · 95% CI -1.17 to 9.88Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.41 · 95% CI -0.14 to 10.96Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.88 · 95% CI 0.36 to 9.40Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.30 · 95% CI -0.22 to 8.83Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.04 · 95% CI -0.65 to 8.72Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.26 · 95% CI -2.42 to 6.94Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 6.90 · 95% CI 1.91 to 11.89Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 6.15 · 95% CI 1.22 to 11.08Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.99 · 95% CI 0.05 to 9.93Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.34 · 95% CI 0.45 to 10.22Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.67 · 95% CI -3.17 to 6.52Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 4.03 · 95% CI -0.86 to 8.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 4.05 · 95% CI -1.18 to 9.27Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 3.76 · 95% CI -1.38 to 8.90Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.18 · 95% CI -1.70 to 12.06Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.61 · 95% CI -1.14 to 12.37Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.21 · 95% CI -5.35 to 4.92Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 1.61 · 95% CI -3.42 to 6.65Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 5.08 · 95% CI -1.19 to 11.36Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 5.30 · 95% CI -0.83 to 11.42Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: 1.30 · 95% CI -4.02 to 6.63Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: 2.93 · 95% CI -2.26 to 8.12Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.34 · 95% CI -7.52 to 4.85Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -1.14 · 95% CI -7.25 to 4.98Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate.
PrimaryChange From Baseline in Reactive Hyperemia Index (RHI) on Day 13

RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values \>1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.

Time frame:
Baseline, Day 13 predose AM
Reported as:
Least squares mean · ratio
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
ratioPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Baseline2.327 ± 1.1181.918 ± 0.5871.683 ± 0.3791.807 ± 0.501
Day 13 predose AM0.282 ± 0.219-0.006 ± 0.1630.177 ± 0.1760.086 ± 0.120
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -0.288 · 95% CI -0.857 to 0.282Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -0.105 · 95% CI -0.708 to 0.498Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -0.196 · 95% CI -0.727 to 0.335Least Squares mean difference and associated 95% CI is from an ANCOVA model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryPost-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay

Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with \< 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \< 180 units indicate impairment of platelet aggregation.

Time frame:
Baseline, Day 8, Day 14
Reported as:
Count of participants · Participants
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
ParticipantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Baseline: <180 PRU000
Baseline: ≥180 PRU51010
PRU Day 8: ≥180 BL, <180 PBL000
PRU Day 8: ≥180 BL, ≥180 PBL51010
PRU Day 14: ≥180 BL, <180 PBL000
PRU Day 14: ≥180 BL, ≥180 PBL51010
PrimaryPost-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay

Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or \> 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.

Time frame:
Baseline, Day 8, Day 14
Reported as:
Count of participants · Participants
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
ParticipantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Baseline: ≤ 549 ARU256
Baseline: > 549 ARU354
Day 8: ≤ 549 BL, ≤ 549 PBL256
Day 8: ≤ 549 BL, > 549 PBL000
Day 8: > 549 BL, ≤ 549 PBL120
Day 8: > 549 BL, > 549 PBL234
Day 14: ≤ 549 BL, ≤ 549 PBL226
Day 14: ≤ 549 BL, > 549 PBL030
Day 14: > 549 BL, ≤ 549 PBL001
Day 14: > 549 BL, > 549 PBL353
PrimaryChange From Study Baseline Over Time in Platelet Function Assessments: PRU Assay

The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \<180 PRU indicate impairment of platelet aggregation.

Time frame:
Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)
Reported as:
Mean · PRU
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
PRUPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline (Day 1 predose)304.0 ± 48.8283.6 ± 43.1294.4 ± 36.9
Change at Day 8-9.4 ± 47.88.2 ± 31.4-0.7 ± 36.4
Change at Day 14-4.4 ± 38.124.4 ± 38.28.5 ± 24.5
PrimaryChange From Study Baseline Over Time in Platelet Function Assessments: ARU Assay

Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.

Time frame:
Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)
Reported as:
Mean · ARU
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
ARUPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline (Day 1 predose)571.4 ± 82.5557.4 ± 76.3524.6 ± 89.5
Change at Day 8-8.0 ± 58.5-16.2 ± 50.918.7 ± 29.4
Change at Day 1410.2 ± 19.830.2 ± 34.9-11.7 ± 34.9
PrimaryPercent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin

Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.

Time frame:
Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15
Reported as:
Least squares mean · percent change
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
percent changePlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDIW-1973 40 mg Total Daily Dose (Overall)
Study Baseline (Day 1 predose)7.350 ± 5.2366.646 ± 3.4037.187 ± 5.6846.962 ± 4.681
Day 8-4.284 ± 20.823-27.473 ± 18.639-18.318 ± 15.735-22.895 ± 12.191
Day 15-12.839 ± 12.565-38.228 ± 11.263-34.015 ± 10.270-36.121 ± 7.609
Statistical analysis
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -23.188 · 95% CI -84.130 to 37.753Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -14.033 · 95% CI -70.883 to 42.817Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -18.611 · 95% CI -71.204 to 33.982Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg BID/QD · Least squares mean difference: -25.389 · 95% CI -62.551 to 11.774Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg QD/QD · Least squares mean difference: -21.176 · 95% CI -56.879 to 14.527Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
  • Placebo vs IW-1973 40 mg Total Daily Dose (Overall) · Least squares mean difference: -23.282 · 95% CI -55.618 to 9.053Least Squares mean difference and associated 95% confidence interval (CI) is from an analysis of covariance (ANCOVA) model with treatment as fixed effect and baseline as covariate. Standard Error of the Mean=Standard Error of the LS Mean Difference.
PrimaryIW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7

Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.

Time frame:
Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Reported as:
Mean · h*ng/mL
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
h*ng/mLIW-1973 40 mg BID/QD: 20 mg AMIW-1973 40 mg BID/QD: 20 mg PMIW-1973 40 mg QD/QD: 40 mg AM
Day 1362 ± 88339 ± 1341190 ± 499
Day 7795 ± 186—2200 ± 591
PrimaryIW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Time frame:
Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Reported as:
Mean · ng/mL
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
ng/mLIW-1973 40 mg BID/QD: 20 mg AMIW-1973 40 mg BID/QD: 20 mg PMIW-1973 40 mg QD/QD: 40 mg AM
Day 173.8 ± 18.947.8 ± 22.2181 ± 107
Day 7117 ± 32.6—242 ± 80.0
PrimaryIW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Time frame:
Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Reported as:
Median · hours
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
hoursIW-1973 40 mg BID/QD: 20 mg AMIW-1973 40 mg BID/QD: 20 mg PMIW-1973 40 mg QD/QD: 40 mg AM
Day 11.0 (1.0 to 3.0)3.0 (3.0 to 11.9)2.0 (1.0 to 6.0)
Day 71.0 (1.0 to 3.0)—1.0 (1.0 to 6.0)
PrimaryIW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Time frame:
Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose
Reported as:
Mean · ng/mL
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
ng/mLIW-1973 40 mg BID/QD: 20 mg AMIW-1973 40 mg BID/QD: 20 mg PMIW-1973 40 mg QD/QD: 40 mg AM
Day 111.6 ± 4.2919.6 ± 5.0415.6 ± 5.24
Day 221.0 ± 5.97——
Day 6—48.4 ± 10.153.7 ± 14.5
Day 745.6 ± 14.552.4 ± 12.857.2 ± 14.9
PrimaryIW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14
Time frame:
Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Mean · h*mg/mL
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14
h*mg/mLIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
Day 81210 ± 2641540 ± 482
Day 1417100 ± 698023600 ± 8950
PrimaryIW-1973 Pharmacokinetics: AUCtau on Day 14
Time frame:
Day 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Mean · ng/mL
IW-1973 Pharmacokinetics: AUCtau on Day 14
ng/mLIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
IW-1973 Pharmacokinetics: AUCtau on Day 142080 ± 4422910 ± 770
PrimaryIW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Time frame:
Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Median · hours
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
hoursIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
Day 81.0 (1.0 to 3.0)1.0 (1.0 to 6.2)
Day 141.0 (1.0 to 3.0)3.0 (1.0 to 6.0)
PrimaryIW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Time frame:
Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Mean · ng/mL
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
ng/mLIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
Day 8198 ± 56.8229 ± 90.6
Day 14181 ± 46.8250 ± 139
PrimaryIW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Time frame:
Days 13 and 14: predose
Reported as:
Mean · ng/mL
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
ng/mLIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
Day 1356.8 ± 19.582.4 ± 22.7
Day 1465.7 ± 23.090.7 ± 26.2
PrimaryIW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
Time frame:
Day 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Mean · L/h
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
L/hIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 1420.0 ± 4.3414.7 ± 3.89
PrimaryIW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
Time frame:
Day 14: 1, 3, 6h (± 5 min) postdose
Reported as:
Mean · L
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
LIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 145570 ± 15303880 ± 1370
PrimaryIW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
Time frame:
Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42)
Reported as:
Mean · hours
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
hoursIW-1973 40 mg BID/QD: 40 mg AMIW-1973 40 mg QD/QD: 40 mg AM
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)197 ± 57.4183 ± 43.4
PrimaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.

Time frame:
From first dose of study drug to End of Trial Visit (42 [± 3] days)
Reported as:
Number · participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
TEAE568
SAE010
Severe TEAE010
Moderate TEAE000
Mild TEAE568
TEAE Considered Study Drug Related136
TEAE Considered Not Study Drug Related467
TEAE Resulting in Study Discontinuation010
TEAE Resulting in Death000
AECI Related to Bleeding010
AECI Related to Hypotension110
PrimaryNumber of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
Time frame:
From first dose of study drug to End of Trial Visit (42 [± 3] days)
Reported as:
Number · participants
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results011
PrimaryNumber of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values

Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine diastolic blood pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine heart rate (SHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ \> 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ \> 15 mmHg from supine to standing. Orthostatic HR: ↓ \> 30 bpm from supine to standing.

Time frame:
From first dose of study drug to End of Trial Visit (42 [± 3] days)
Reported as:
Number · participants
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg000
SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg010
SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg000
SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg020
SHR: ≥ 110 bpm and ↑ from BL ≥ 20 bpm120
SHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm100
StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg000
StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg020
StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg000
StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg010
StHR: ≥ 120 bpm and ↑ from BL ≥ 25 bpm011
StHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm000
Orthostatic SBP: ↓ > 20 mmHg, Supine to Standing243
Orthostatic DBP: ↓ > 15 mmHg, Supine to Standing110
Orthostatic HR: ↑ > 30 bpm, Supine to Standing221
PrimaryNumber of Participants With Clinically Significant Post-Randomization Physical Examination Findings

Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.

Time frame:
Post-randomization to End of Trial Visit (42 [± 3] days)
Reported as:
Number · participants
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings000
PrimaryNumber of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
Time frame:
From first dose of study drug to End of Trial Visit (42 [± 3] days)
Reported as:
Number · participants
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
participantsPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results000
PrimaryChange From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Time frame:
Study Baseline, Day 15/Discharge, Day 42/End of Trial
Reported as:
Mean · mL/min/1.73m^2
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
mL/min/1.73m^2PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Study Baseline103.045 ± 7.54289.014 ± 19.72980.373 ± 19.716
Day 15/Discharge0.158 ± 4.050-2.232 ± 7.2751.663 ± 5.803
Day 42/End of Trial-3.727 ± 10.262-8.905 ± 4.293-5.587 ± 6.196

Adverse events

Collected over From first dose of study drug to End of Trial Visit (42 [± 3] days). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/6 (0%)0/6 (0%)5/6 (83.3%)
IW-1973 40 mg BID/QD0/10 (0%)1/10 (10%)6/10 (60%)
IW-1973 40 mg QD/QD0/10 (0%)0/10 (0%)8/10 (80%)
Most frequent serious events
Most frequent serious events
EventPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Upper gastrointestinal haemorrhageGastrointestinal disorders0/61/100/10
Most frequent other events
Showing 10 of 32
Most frequent other events
EventPlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QD
Injection site haemorrhageGeneral disorders3/60/101/10
HypoglycaemiaMetabolism and nutrition disorders2/62/103/10
HeadacheNervous system disorders2/62/103/10
NauseaGastrointestinal disorders0/62/103/10
DiarrhoeaGastrointestinal disorders1/60/103/10
Abdominal painGastrointestinal disorders0/60/102/10
PseudohypoglycaemiaMetabolism and nutrition disorders1/60/100/10
Limb discomfortMusculoskeletal and connective tissue disorders1/60/100/10
DizzinessNervous system disorders1/61/100/10
TremorNervous system disorders1/60/100/10

Baseline characteristics

Age, Customized
Age, Customized(Participants)PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDTotal
40 to < 65 years old46717
>= 65 years old2439
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDTotal
Female44513
Male26513
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDTotal
Hispanic or Latino52310
Not Hispanic or Latino18716
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDTotal
White67720
Asian0123
Black or African American0213
Percentage of Participants With Baseline Supine BP Less Than 130/80 mmHg
Percentage of Participants With Baseline Supine BP Less Than 130/80 mmHg(percentage of participants)PlaceboIW-1973 40 mg BID/QDIW-1973 40 mg QD/QDTotal
Number33.380.060.070.0
08

Study locations

1 site
  • ProSciento, Inc.
    Chula Vista, California 91911, United States
09

References and documents

Publications

  • Hanrahan JP, Seferovic JP, Wakefield JD, Wilson PJ, Chickering JG, Jung J, Carlson KE, Zimmer DP, Frelinger AL 3rd, Michelson AD, Morrow L, Hall M, Currie MG, Milne GT, Profy AT. An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension. Diabetologia. 2020 Apr;63(4):733-743. doi: 10.1007/s00125-019-05062-x. Epub 2019 Dec 19. PubMed 31858186 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Undecided

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Feb 2017 to primary completion in Aug 2017, 5 months.

Results were first posted in Aug 2020, 3 years after primary completion. A results delay was requested in Jul 2018.

Of 194 industry-sponsored phase 2 interventional studies under Diabetes Mellitus, Type 2, half reached primary completion within 13 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 18. This study's 5 months is below that.

Counting every sponsor, half of 293 studies reached it within 15 months; a quarter within 11 and three quarters within 27.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 8, 2017
First posted
Mar 27, 2017
StartActual
Feb 28, 2017
Primary completionActual
Aug 3, 2017
CompletionActual
Aug 3, 2017
Results delay requested
Jul 17, 2018
Results first posted
Aug 31, 2020
Last update
Aug 31, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 31, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03091920
Lead sponsor
Cyclerion Therapeutics
Responsible party
Sponsor
First posted
Mar 27, 2017
Start date
Feb 28, 2017
Primary completion
Aug 3, 2017
Completion
Aug 3, 2017
Results posted
Aug 31, 2020
Last update
Aug 31, 2020

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Praliciguat

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