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CompletedNCT02906579Updated Apr 16, 2020Results posted

A Phase 2 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 Matching Placebo and IW-1973 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 65 Years. Per ClinicalTrials.gov, last updated 2020-04-16.

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

Phase
Phase 2
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
30 Years to 65 Years
Sex
All
01

Study summary

To evaluate the impact of escalating doses of IW-1973 on endothelial function [using EndoPAT to measure fingertip small vessel pulse volume], blood pressure (BP), and heart rate.

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 11 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 65 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/m2 at the Screening Visit
  • Women of must have a negative pregnancy test at the time of check-in and must agree to use double-barrier throughout the duration of the study
  • Patient's health is stable with no findings on a physical examination
  • Patient has type 2 (ie adult onset) diabetes mellitus diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit, and an entry that does not mandate prompt intervention for improved control
  • Patient has hypertension diagnosed by a physician or nurse practitioner > 6 months before the Screening Visit and BP within the protocol's acceptable range
  • Patients must be on a stable regimen for glycemic control, and a stable regimen for hypertension control that includes an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)
  • Patient has abnormal endothelial function measured by the EndoPAT
  • 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 soluble guanylate cyclase (sGC) stimulator, could increase the risk of hypotension
  • Patient has evidence of severe or active end-organ damage attributable to diabetes
  • Patient has severe renal insufficiency, has undergone renal transplantation, or has planned renal transplantation
  • 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.

HbA1c

A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    IW-1973

    Placebo taken once daily Day 1-Day 3; 10 mg IW-1973 take once daily Day 4-Day 6; 20 mg IW-1973 taken once daily Day 7-Day 9; 30 mg IW-1973 taken once daily Day 10-Day 12; 40 mg IW-1973 taken once daily Day 13-Day 15; 50 mg IW-1973 taken once daily Day 16-Day 18

    Drug: Matching Placebo · Drug: IW-1973

Interventions

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, 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.

    Time frame: From first dose of study drug through end of trial (Day 46 [±3 days])

  2. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 19

  3. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 32

  4. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 19

  5. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 32

  6. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 19

  7. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 32

  8. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 19

  9. Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)

    Study baseline is defined as the Day -1 assessment.

    Time frame: Baseline, Day 32

  10. Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle

    Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

    Time frame: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

  11. Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle

    Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

    Time frame: Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)

  12. Number of Participants With Notable Changes in Post Baseline Vital Signs 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 pulse rate (SPR): ≥ 110 beats per minute (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 pulse rate (StPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.

    Time frame: Up to Day 32

  13. Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values

    Systolic blood pressure (SBP): Decrease of \> 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of \> 10 mmHg from supine to standing Pulse rate (PR): Increase of \> 20 bpm from supine to standing.

    Time frame: Up to Day 32

  14. Change From Baseline Over Time in Respiratory Rate

    Time frame: Baseline, Day 19, Day 32

  15. Change From Baseline Over Time in Temperature

    Time frame: Baseline, Day 19, Day 32

  16. Change From Baseline Over Time in Weight

    Time frame: Baseline, Day 19, Day 32

  17. Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)

    Time frame: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

  18. Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)

    Time frame: Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19

  19. Change From Study Baseline Over Time in Supine Pulse

    Study baseline is defined as the Day -1 assessment.

    Time frame: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

  20. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse

    Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

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

    Study baseline is defined as the Day -1 assessment.

    Time frame: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

  22. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure

    Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

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

    Study baseline is defined as the Day -1 assessment.

    Time frame: Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

  24. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure

    Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h

  25. Orthostatic Pulse Over Time

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

    Time frame: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

  26. Orthostatic Systolic Blood Pressure Over Time

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

    Time frame: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

  27. Orthostatic Diastolic Blood Pressure Over Time

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

    Time frame: Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h

  28. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure

    Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

  29. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure

    Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

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

    Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2

  31. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure

    Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

  32. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure

    Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

  33. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure

    Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2

  34. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure

    Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

  35. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure

    Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

  36. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure

    Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2

  37. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse

    Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs

  38. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse

    Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs

  39. Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse

    Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle); Cycle Day 2

  40. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse

    Time frame: Follow-up Visit Day 32 (± 2 days)

  41. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure

    Time frame: Follow-up Visit Day 32 (± 2 days)

  42. Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure

    Time frame: Follow-up Visit Day 32 (± 2 days)

  43. Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)

    Study baseline is defined as the Day -1 assessment. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

    Time frame: Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h

  44. Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI

    Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction. Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h

  45. Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI

    Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

    Time frame: Follow-up Visit Day 32 (± 2 days)

  46. Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation

    Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle. Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation. Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data.

    Time frame: Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h

07

Results

Posted Apr 16, 2020
Limitations and caveats
No separate placebo control. 2 of 11 enrolled participants discontinued prematurely. Participants were confined, diet and activity controlled. Multiple dose-escalation design had no washout period between dose cycles. EndoPAT device was exploratory.

Participant flow

Participant flow — Overall Study
MilestoneAll Participants
Started11
Completed cycle 1 (placebo)11
Completed cycle 2 (10 mg iw-1973)11
Completed cycle 3 (20 mg iw-1973)11
Completed cycle 4 (30 mg iw-1973)10
Completed cycle 5 (40 mg iw-1973)9
Completed cycle 6 (50 mg iw-1973)9
Completed9
Not completed2
Withdrew: Adverse event1
Withdrew: Physician decision1

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, 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.

Time frame:
From first dose of study drug through end of trial (Day 46 [±3 days])
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to TEAEs
ParticipantsControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
≥1 TEAE332432
SAE000000
Deaths000000
Discontinuations (DCs) due to AEs001000
DCs Due to Trough Blood Pressure Decline001100
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 19
Reported as:
Mean · mg/dL
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Discharge Day (Day 19)
mg/dLAll Participants
Cholesterol: Day 19/Discharge141.7 ± 39.6
Cholesterol: Change at Day 19/Discharge-43.3 ± 35.1
Glucose: Day 19/Discharge116.82 ± 25.43
Glucose: Change at Day 19/Discharge-26.45 ± 25.25
HDL-C: Day 19/Discharge44.36 ± 10.74
HDL-C: Change at Day 19/Discharge-5.91 ± 7.73
LDL-C: Day 19/Discharge73.09 ± 34.69
LDL-C: Change at Day 19/Discharge-34.36 ± 28.88
Triglycerides: Day 19/Discharge121.73 ± 46.10
Triglycerides: Change at Day 19/Discharge-16.00 ± 42.45
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 32
Reported as:
Mean · mg/dL
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Cholesterol, Glucose, HDL-C, LDL-C, and Triglycerides at Follow-Up (Day 32)
mg/dLAll Participants
Cholesterol: Day 32/Follow-Up183.1 ± 48.6
Cholesterol: Change at Day 32/Follow-Up-1.9 ± 27.1
Glucose: Day 32/Follow-Up154.27 ± 48.54
Glucose: Change at Day 32/Follow-Up11.00 ± 41.47
HDL-C: Day 32/Follow-Up48.18 ± 10.32
HDL-C: Change at Day 32/Follow-Up-2.09 ± 6.88
LDL-C: Day 32/Follow-Up107.27 ± 42.11
LDL-C: Change at Day 32/Follow-Up-0.18 ± 23.84
Triglycerides: Day 32/Follow-Up138.09 ± 46.26
Triglycerides: Change at Day 32/Follow-Up0.36 ± 52.94
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 19
Reported as:
Mean · U/L
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase at Discharge Day (Day 19)
U/LAll Participants
GGT: Day 19/Discharge28.3 ± 17.2
GGT: Change at Day 19/Discharge-7.9 ± 15.9
Lactate Dehydrogenase: Day 19/Discharge135.7 ± 18.2
Lactate Dehydrogenase: Change at Day 19/Discharge-27.4 ± 21.2
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 32
Reported as:
Mean · U/L
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in GGT and Lactate Dehydrogenase at Follow-Up (Day 32)
U/LAll Participants
GGT: Day 32/Follow-Up53.6 ± 83.9
GGT: Change at Day 32/Follow-Up17.5 ± 67.8
Lactate Dehydrogenase: Day 32/Follow-Up171.6 ± 55.2
Lactate Dehydrogenase: Change at Day 32/Follow-Up8.5 ± 46.4
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 19
Reported as:
Mean · percent
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Discharge Day (Day 19)
percentAll Participants
Discharge Day (Day 19)7.27 ± 1.53
Change at Discharge Day (Day 19)-0.40 ± 0.54
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 32
Reported as:
Mean · percent
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Hemoglobin A1c at Follow-Up (Day 32)
percentAll Participants
Follow-Up (Day 32)7.54 ± 1.49
Change at Follow-Up (Day 32)-0.14 ± 0.49
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 19
Reported as:
Mean · µIU/mL
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Discharge Day (Day 19)
µIU/mLAll Participants
Discharge Day (Day 19)17.45 ± 14.20
Change at Discharge Day (Day 19)-0.05 ± 5.31
PrimaryCertain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)

Study baseline is defined as the Day -1 assessment.

Time frame:
Baseline, Day 32
Reported as:
Mean · µIU/mL
Certain Clinical Chemistry Laboratory Parameters: Overall Changes From Study Baseline in Insulin at Follow-Up (Day 32)
µIU/mLAll Participants
Follow-Up (Day 32)23.81 ± 18.81
Change at Follow-Up (Day 32)6.31 ± 11.18
PrimaryChange From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle

Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Time frame:
Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)
Reported as:
Mean · mg/dL
Change From Time-Matched Baseline in Fasting Blood Glucose on Day 2 of Each Dose Cycle
mg/dL10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline142.3 ± 32.6142.3 ± 32.6144.1 ± 33.8147.7 ± 33.8147.7 ± 33.8
Cycle Day 2 Change-12.0 ± 10.3-13.4 ± 9.9-21.1 ± 16.0-24.3 ± 16.9-25.3 ± 15.9
PrimaryChange From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle

Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle. Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Time frame:
Time-Matched Baseline (Day 2 Placebo Cycle), Day 2 of Each Dose Cycle (Days 5, 8, 11, 14, 17)
Reported as:
Mean · µIU/mL
Change From Time-Matched Baseline in Serum Insulin on Day 2 of Each Dose Cycle
µIU/mL10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline17.35 ± 10.7017.35 ± 10.7017.37 ± 11.2814.32 ± 6.2114.32 ± 6.21
Cycle Day 2 Change0.20 ± 5.04-0.40 ± 6.26-2.61 ± 3.11-2.49 ± 5.65-2.70 ± 4.20
PrimaryNumber of Participants With Notable Changes in Post Baseline Vital Signs 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 pulse rate (SPR): ≥ 110 beats per minute (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 pulse rate (StPR): ≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.

Time frame:
Up to Day 32
Reported as:
Count of participants · Participants
Number of Participants With Notable Changes in Post Baseline Vital Signs Values
ParticipantsControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg000000
SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg001200
SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg000000
SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg000000
SPR: ≥ 110 bpm and ↑ from BL000000
SPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm000000
StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg000000
StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg000010
StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg000000
StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg000000
StPR: ≥ 120 bpm and ↑ from BL000000
StPR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm000000
PrimaryNumber of Participants With Notable Post Baseline Orthostatic Vital Signs Values

Systolic blood pressure (SBP): Decrease of \> 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of \> 10 mmHg from supine to standing Pulse rate (PR): Increase of \> 20 bpm from supine to standing.

Time frame:
Up to Day 32
Reported as:
Count of participants · Participants
Number of Participants With Notable Post Baseline Orthostatic Vital Signs Values
ParticipantsControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
SBP: Decrease of > 20 mmHg, supine to standing000000
DBP: Decrease of > 10 mmHg from supine to standin001010
PR: Increase of > 20 bpm from supine to standing343533
PrimaryChange From Baseline Over Time in Respiratory Rate
Time frame:
Baseline, Day 19, Day 32
Reported as:
Mean · breaths/min
Change From Baseline Over Time in Respiratory Rate
breaths/minAll Participants
Change at Day 19/Discharge-0.7 ± 1.8
Change at Day 32/Follow-Up-1.5 ± 2.7
PrimaryChange From Baseline Over Time in Temperature
Time frame:
Baseline, Day 19, Day 32
Reported as:
Mean · degrees celcius
Change From Baseline Over Time in Temperature
degrees celciusAll Participants
Change at Day 19/Discharge0.12 ± 0.19
Change at Day 32/Follow-Up-0.03 ± 0.20
PrimaryChange From Baseline Over Time in Weight
Time frame:
Baseline, Day 19, Day 32
Reported as:
Mean · kg
Change From Baseline Over Time in Weight
kgAll Participants
Change at Day 19/Discharge-3.47 ± 2.16
Change at Day 32/Follow-Up-1.40 ± 1.61
PrimaryNumber of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)
Time frame:
Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)
ParticipantsAll Participants
Number of Participants With Clinically Significant Findings or Shifts in Baseline in Electrocardiograms (ECGs)0
PrimaryNumber of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
Time frame:
Study Baseline, Cycle Day 1: 0 (≤ 15m) predose; 1h, 4h (± 15m) postdose; Day 19
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
ParticipantsControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Number of Participants With Clinically Significant Findings or Shifts in Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)000000
PrimaryChange From Study Baseline Over Time in Supine Pulse

Study baseline is defined as the Day -1 assessment.

Time frame:
Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · bpm
Change From Study Baseline Over Time in Supine Pulse
bpmControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Study Baseline72.0 ± 15.972.0 ± 15.972.0 ± 15.972.7 ± 16.673.2 ± 17.573.2 ± 17.5
Change at Cycle Day 1, 0 h-5.5 ± 7.6-6.5 ± 11.6-5.8 ± 11.1-7.2 ± 11.0-4.9 ± 12.1-6.3 ± 13.7
Change at Cycle Day 1, 1 h-0.1 ± 8.7-1.9 ± 9.81.7 ± 12.75.7 ± 12.71.0 ± 9.44.8 ± 12.1
Change at Cycle Day 1, 2 h-1.8 ± 7.63.4 ± 8.96.3 ± 11.711.9 ± 14.113.9 ± 10.99.0 ± 12.1
Change at Cycle Day 1, 4 h-3.5 ± 9.4-2.2 ± 10.71.7 ± 9.50.7 ± 10.63.7 ± 7.50.2 ± 8.8
Change at Cycle Day 1, 8 h-3.2 ± 9.72.1 ± 12.30.8 ± 10.2-1.4 ± 9.3-1.7 ± 11.7-0.2 ± 8.9
Change at Cycle Day 1, 12 h-2.3 ± 8.44.1 ± 10.42.9 ± 9.60 ± 9.43.2 ± 12.90.8 ± 10.2
Change at Cycle Day 3, 0 h-4.1 ± 11.7-6.2 ± 10.7-5.1 ± 11.2-5.4 ± 10.8-6.8 ± 12.2-6.3 ± 11.4
Change at Cycle Day 3, 1 h-1.8 ± 9.33.9 ± 11.95.5 ± 11.76.1 ± 8.48.8 ± 15.210.0 ± 13.2
Change at Cycle Day 3, 2 h2.0 ± 9.14.5 ± 11.37.2 ± 8.99.1 ± 10.711.1 ± 12.611.6 ± 13.1
Change at Cycle Day 3, 8 h-1.0 ± 11.20.6 ± 9.3-1.6 ± 11.7-1.2 ± 7.8-0.3 ± 11.44.2 ± 14.8
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · bpm
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Pulse
bpm10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time Matched Baseline (Cycle Day 1, 0 h)66.5 ± 10.866.5 ± 10.866.7 ± 11.367.0 ± 12.067.0 ± 12.0
Change at Cycle Day 1, 0 h-1.1 ± 5.5-0.4 ± 5.2-1.2 ± 5.71.3 ± 7.0-0.1 ± 8.4
Time Matched Baseline (Cycle Day 1, 1 h)71.9 ± 12.671.9 ± 12.672.6 ± 13.073.4 ± 13.573.4 ± 13.5
Change at Cycle Day 1, 1 h-1.8 ± 3.21.8 ± 5.05.8 ± 4.70.8 ± 4.54.6 ± 4.3
Time Matched Baseline (Cycle Day 1, 2 h)70.2 ± 11.770.2 ± 11.770.8 ± 12.271.8 ± 12.571.8 ± 12.5
Change at Cycle Day 1, 2 h5.2 ± 4.38.1 ± 6.713.8 ± 7.215.3 ± 7.210.4 ± 5.8
Time Matched Baseline (Cycle Day 1, 4 h)68.5 ± 10.468.5 ± 10.468.3 ± 10.968.4 ± 11.668.4 ± 11.6
Change at Cycle Day 1, 4 h1.3 ± 6.25.2 ± 7.75.1 ± 7.58.4 ± 6.85.0 ± 4.5
Time Matched Baseline (Cycle Day 1, 8 h)68.8 ± 10.968.8 ± 10.968.6 ± 11.568.9 ± 12.168.9 ± 12.1
Change at Cycle Day 1, 8 h5.3 ± 6.34.0 ± 3.82.7 ± 4.82.7 ± 5.84.1 ± 4.9
Time Matched Baseline (Cycle Day 1, 12 h)69.7 ± 11.569.7 ± 11.570.0 ± 12.170.2 ± 12.870.2 ± 12.8
Change at Cycle Day 1, 12 h6.4 ± 6.35.2 ± 5.92.7 ± 4.06.2 ± 7.33.8 ± 5.2
Time Matched Baseline (Cycle Day 3, 0 h)67.9 ± 11.967.9 ± 11.966.6 ± 11.767.1 ± 12.367.1 ± 12.3
Change at Cycle Day 3, 0 h-2.1 ± 4.2-1.0 ± 6.40.7 ± 6.1-0.7 ± 2.9-0.2 ± 3.8
Time Matched Baseline (Cycle Day 3, 1 h)70.2 ± 13.670.2 ± 13.670.6 ± 14.371.2 ± 15.071.2 ± 15.0
Change at Cycle Day 3, 1 h5.7 ± 8.67.4 ± 9.98.2 ± 5.410.8 ± 6.912.0 ± 6.4
Time Matched Baseline (Cycle Day 3, 2 h)73.8 ± 15.073.8 ± 15.074.2 ± 15.975.6 ± 16.475.6 ± 16.4
Change at Cycle Day 3, 2 h3.7 ± 6.25.1 ± 6.28.0 ± 6.310.3 ± 6.910.4 ± 8.3
Time Matched Baseline (Cycle Day 3, 8 h)71.0 ± 12.971.0 ± 12.969.8 ± 14.170.8 ± 14.170.8 ± 14.1
Change at Cycle Day 3, 8 h1.6 ± 5.9-0.6 ± 8.4-0.6 ± 5.22.1 ± 6.56.7 ± 14.4
PrimaryChange From Study Baseline Over Time in Supine Systolic Blood Pressure

Study baseline is defined as the Day -1 assessment.

Time frame:
Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · mmHg
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
mmHgControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Study Baseline136.3 ± 12.9136.3 ± 12.9136.3 ± 12.9133.9 ± 10.8132.9 ± 10.9132.9 ± 10.9
Change at Cycle Day 1, 0 h-8.9 ± 9.9-9.8 ± 19.6-18.7 ± 16.4-16.1 ± 10.3-15.0 ± 14.3-16.1 ± 15.7
Change at Cycle Day 1, 1 h-14.8 ± 13.0-18.1 ± 18.7-25.6 ± 16.8-24.0 ± 13.5-22.9 ± 13.2-27.2 ± 13.5
Change at Cycle Day 1, 2 h-17.3 ± 11.5-22.5 ± 17.8-27.5 ± 15.7-27.9 ± 14.5-26.6 ± 16.8-27.2 ± 15.1
Change at Cycle Day 1, 4 h-13.5 ± 10.7-18.4 ± 13.0-24.4 ± 13.4-23.9 ± 15.1-27.0 ± 14.7-25.3 ± 16.7
Change at Cycle Day 1, 8 h-16.6 ± 12.0-17.7 ± 13.5-25.3 ± 11.5-21.7 ± 13.5-24.3 ± 14.4-30.6 ± 15.5
Change at Cycle Day 1, 12 h-14.4 ± 12.7-15.5 ± 16.8-23.8 ± 13.4-20.9 ± 14.2-22.3 ± 15.6-23.4 ± 17.4
Change at Cycle Day 3, 0 h-13.3 ± 15.0-13.0 ± 16.1-18.3 ± 16.1-18.5 ± 15.1-16.9 ± 11.5-18.8 ± 16.7
Change at Cycle Day 3, 1 h-16.1 ± 15.6-22.1 ± 17.8-24.9 ± 21.1-26.3 ± 15.1-24.7 ± 16.3-25.7 ± 13.5
Change at Cycle Day 3, 2 h-16.1 ± 15.5-23.2 ± 16.7-27.7 ± 18.7-28.8 ± 15.7-28.0 ± 12.8-26.6 ± 12.0
Change at Cycle Day 3, 8 h-15.4 ± 15.0-20.5 ± 14.6-23.5 ± 16.3-26.2 ± 12.5-24.9 ± 14.3-20.6 ± 13.5
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Systolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time Matched Baseline (Cycle Day 1, 0 h)127.4 ± 9.1127.4 ± 9.1126.3 ± 8.9125.2 ± 8.7125.2 ± 8.7
Change at Cycle Day 1, 0 h-0.9 ± 14.0-9.8 ± 9.9-8.5 ± 7.9-7.3 ± 7.4-8.4 ± 11.8
Time Matched Baseline (Cycle Day 1, 1 h)121.5 ± 11.3121.5 ± 11.3121.2 ± 11.8119.7 ± 11.5119.7 ± 11.5
Change at Cycle Day 1, 1 h-3.3 ± 12.1-10.8 ± 11.1-11.3 ± 10.6-9.7 ± 11.4-14.0 ± 11.5
Time Matched Baseline (Cycle Day 1, 2 h)119.0 ± 8.8119.0 ± 8.8117.6 ± 7.9117.2 ± 8.3117.2 ± 8.3
Change at Cycle Day 1, 2 h-5.3 ± 11.4-10.3 ± 11.4-11.6 ± 7.5-10.9 ± 8.1-11.6 ± 6.8
Time Matched Baseline (Cycle Day 1, 4 h)122.7 ± 6.4122.7 ± 6.4121.8 ± 5.9120.7 ± 4.9120.7 ± 4.9
Change at Cycle Day 1, 4 h-4.8 ± 8.8-10.8 ± 11.3-11.8 ± 11.6-14.8 ± 10.4-13.1 ± 10.4
Time Matched Baseline (Cycle Day 1, 8 h)119.6 ± 9.9119.6 ± 9.9117.3 ± 6.5116.4 ± 6.3116.4 ± 6.3
Change at Cycle Day 1, 8 h-1.1 ± 12.8-8.6 ± 11.1-5.1 ± 11.4-7.9 ± 11.4-14.1 ± 9.3
Time Matched Baseline (Cycle Day 1, 12 h)121.9 ± 10.7121.9 ± 10.7120.7 ± 10.4119.0 ± 9.5119.0 ± 9.5
Change at Cycle Day 1, 12 h-1.2 ± 13.7-9.5 ± 9.8-7.7 ± 10.7-8.4 ± 9.2-9.6 ± 12.5
Time Matched Baseline (Cycle Day 3, 0 h)123.0 ± 11.4123.0 ± 11.4124.0 ± 11.5124.3 ± 12.1124.3 ± 12.1
Change at Cycle Day 3, 0 h0.3 ± 11.3-5.0 ± 12.2-8.6 ± 10.8-8.3 ± 10.2-10.2 ± 16.6
Time Matched Baseline (Cycle Day 3, 1 h)120.2 ± 12.6120.2 ± 12.6121.0 ± 12.9121.3 ± 13.7121.3 ± 13.7
Change at Cycle Day 3, 1 h-6.0 ± 7.9-8.8 ± 10.4-13.4 ± 11.3-13.1 ± 15.7-14.1 ± 10.6
Time Matched Baseline (Cycle Day 3, 2 h)119.2 ± 10.8119.2 ± 10.8119.4 ± 11.5120.4 ± 11.9120.4 ± 11.9
Change at Cycle Day 3, 2 h-5.5 ± 6.8-10.4 ± 6.0-13.9 ± 5.0-16.3 ± 9.5-14.8 ± 4.7
Time Matched Baseline (Cycle Day 3, 8 h)120.9 ± 12.0120.9 ± 12.0120.6 ± 13.2122.1 ± 13.1122.1 ± 13.1
Change at Cycle Day 3, 8 h-5.1 ± 10.3-8.1 ± 9.2-12.1 ± 10.6-14.1 ± 10.4-9.8 ± 13.9
PrimaryChange From Study Baseline Over Time in Supine Diastolic Blood Pressure

Study baseline is defined as the Day -1 assessment.

Time frame:
Study Baseline; Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · mmHg
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
mmHgControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Study Baseline80.4 ± 5.980.4 ± 5.980.4 ± 5.979.9 ± 6.078.2 ± 2.978.2 ± 2.9
Change at Cycle Day 1, 0 h-3.3 ± 5.1-4.4 ± 9.2-6.9 ± 6.9-6.4 ± 6.8-6.3 ± 5.6-5.9 ± 6.1
Change at Cycle Day 1, 1 h-6.8 ± 6.8-7.9 ± 8.4-12.5 ± 8.2-13.3 ± 7.0-11.3 ± 5.5-13.7 ± 6.0
Change at Cycle Day 1, 2 h-8.4 ± 7.4-10.9 ± 9.4-12.9 ± 7.5-16.3 ± 8.2-11.7 ± 6.6-13.3 ± 5.9
Change at Cycle Day 1, 4 h-8.2 ± 4.9-8.2 ± 7.3-10.1 ± 5.8-11.7 ± 6.6-12.0 ± 4.9-10.8 ± 5.5
Change at Cycle Day 1, 8 h-7.2 ± 7.5-6.7 ± 8.7-11.5 ± 6.3-10.1 ± 8.8-8.4 ± 7.7-13.3 ± 6.8
Change at Cycle Day 1, 12 h-6.5 ± 6.6-8.6 ± 8.7-9.7 ± 10.6-10.3 ± 9.7-9.9 ± 6.8-11.0 ± 9.4
Change at Cycle Day 3, 0 h-4.6 ± 6.7-2.6 ± 6.9-5.6 ± 7.1-7.0 ± 6.5-7.4 ± 5.4-5.3 ± 6.8
Change at Cycle Day 3, 1 h-7.6 ± 7.9-10.9 ± 9.1-14.1 ± 9.6-13.6 ± 8.8-13.3 ± 6.3-13.2 ± 6.3
Change at Cycle Day 3, 2 h-4.8 ± 8.6-10.5 ± 8.9-13.5 ± 8.4-12.3 ± 10.7-12.2 ± 5.6-16.3 ± 5.3
Change at Cycle Day 3, 8 h-7.5 ± 7.8-9.1 ± 8.5-11.2 ± 6.2-12.1 ± 8.3-10.9 ± 5.3-9.4 ± 5.6
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 1, 0 h; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h; Cycle Day 3, 0 h; Cycle Day 3, 1 h; Cycle Day 3, 2 h; Cycle Day 3, 8 h
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Supine Diastolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time Matched Baseline (Cycle Day 1, 0 h)77.1 ± 5.377.1 ± 5.377.0 ± 5.675.7 ± 3.875.7 ± 3.8
Change at Cycle Day 1, 0 h-1.1 ± 6.2-3.6 ± 3.7-3.5 ± 4.4-3.8 ± 2.5-3.3 ± 4.9
Time Matched Baseline (Cycle Day 1, 1 h)73.5 ± 8.073.5 ± 8.074.1 ± 8.272.1 ± 5.672.1 ± 5.6
Change at Cycle Day 1, 1 h-1.1 ± 6.5-5.6 ± 7.4-7.5 ± 7.3-5.2 ± 5.3-7.6 ± 5.8
Time Matched Baseline (Cycle Day 1, 2 h)72.0 ± 5.572.0 ± 5.571.9 ± 5.871.4 ± 5.971.4 ± 5.9
Change at Cycle Day 1, 2 h-2.5 ± 6.0-4.5 ± 5.4-8.3 ± 4.7-4.9 ± 6.8-6.6 ± 5.7
Time Matched Baseline (Cycle Day 1, 4 h)72.2 ± 6.172.2 ± 6.172.5 ± 6.471.0 ± 4.571.0 ± 4.5
Change at Cycle Day 1, 4 h0 ± 7.0-1.9 ± 6.1-4.3 ± 6.6-4.8 ± 6.0-3.6 ± 3.3
Time Matched Baseline (Cycle Day 1, 8 h)73.2 ± 7.373.2 ± 7.371.9 ± 6.270.9 ± 5.770.9 ± 5.7
Change at Cycle Day 1, 8 h0.5 ± 9.9-4.3 ± 8.4-2.1 ± 7.9-1.1 ± 10.6-6.0 ± 6.2
Time Matched Baseline (Cycle Day 1, 12 h)73.8 ± 7.773.8 ± 7.772.9 ± 7.471.3 ± 5.971.3 ± 5.9
Change at Cycle Day 1, 12 h-2.1 ± 7.2-3.2 ± 10.7-3.3 ± 6.8-3.0 ± 5.4-4.1 ± 5.6
Time Matched Baseline (Cycle Day 3, 0 h)75.7 ± 4.375.7 ± 4.376.1 ± 4.475.7 ± 4.475.7 ± 4.4
Change at Cycle Day 3, 0 h2.0 ± 4.4-1.0 ± 4.8-3.2 ± 4.6-4.9 ± 3.3-2.8 ± 6.3
Time Matched Baseline (Cycle Day 3, 1 h)72.7 ± 6.172.7 ± 6.172.9 ± 6.372.6 ± 6.672.6 ± 6.6
Change at Cycle Day 3, 1 h-3.3 ± 4.6-6.5 ± 6.0-6.6 ± 5.9-7.7 ± 7.3-7.6 ± 5.5
Time Matched Baseline (Cycle Day 3, 2 h)75.6 ± 6.375.6 ± 6.375.3 ± 6.775.4 ± 7.175.4 ± 7.1
Change at Cycle Day 3, 2 h-5.1 ± 4.0-8.0 ± 6.4-7.0 ± 6.2-8.5 ± 4.9-13.3 ± 5.1
Time Matched Baseline (Cycle Day 3, 8 h)72.8 ± 6.572.8 ± 6.573.0 ± 6.873.0 ± 6.873.0 ± 6.8
Change at Cycle Day 3, 8 h-1.5 ± 5.5-3.6 ± 4.0-4.8 ± 5.3-5.7 ± 3.9-4.2 ± 5.5
PrimaryOrthostatic Pulse Over Time

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

Time frame:
Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h
Reported as:
Mean · bpm
Orthostatic Pulse Over Time
bpmControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Cycle Day 1, Predose9.7 ± 3.811.6 ± 5.611.0 ± 4.111.9 ± 3.811.0 ± 3.910.4 ± 2.7
Cycle Day 1, 1 h9.7 ± 5.411.5 ± 7.112.6 ± 6.417.8 ± 6.117.8 ± 7.616.0 ± 7.4
Cycle Day 1, 2 h10.9 ± 4.110.6 ± 5.912.3 ± 8.414.6 ± 6.813.9 ± 5.915.6 ± 5.7
Cycle Day 1, 4 h9.5 ± 7.710.3 ± 9.511.0 ± 6.414.6 ± 5.312.3 ± 9.314.8 ± 8.0
Cycle Day 1, 8 h10.8 ± 7.810.3 ± 6.712.7 ± 6.513.0 ± 3.415.2 ± 4.411.0 ± 7.6
Cycle Day 1, 12 h10.7 ± 4.810.6 ± 5.19.9 ± 13.010.8 ± 7.513.0 ± 7.411.3 ± 6.8
PrimaryOrthostatic Systolic Blood Pressure Over Time

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

Time frame:
Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h
Reported as:
Mean · mmHg
Orthostatic Systolic Blood Pressure Over Time
mmHgControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Cycle Day 1, Predose4.4 ± 7.23.7 ± 6.55.9 ± 7.34.0 ± 13.03.4 ± 5.34.2 ± 9.1
Cycle Day 1, 1 h7.0 ± 5.69.1 ± 8.45.2 ± 3.55.8 ± 8.24.0 ± 6.86.2 ± 6.7
Cycle Day 1, 2 h8.5 ± 12.48.2 ± 4.66.2 ± 8.77.3 ± 8.43.3 ± 6.54.6 ± 8.3
Cycle Day 1, 4 h3.6 ± 9.23.2 ± 8.74.2 ± 5.84.3 ± 5.06.3 ± 9.26.7 ± 7.7
Cycle Day 1, 8 h8.4 ± 5.85.4 ± 5.88.1 ± 14.15.5 ± 7.85.6 ± 4.98.0 ± 4.5
Cycle Day 1, 12 h9.7 ± 10.56.2 ± 5.36.0 ± 6.18.0 ± 6.72.1 ± 4.53.4 ± 7.9
PrimaryOrthostatic Diastolic Blood Pressure Over Time

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

Time frame:
Cycle Day 1, Predose; Cycle Day 1, 1 h; Cycle Day 1, 2 h; Cycle Day 1, 4 h; Cycle Day 1, 8 h; Cycle Day 1, 12 h
Reported as:
Mean · mmHg
Orthostatic Diastolic Blood Pressure Over Time
mmHgControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Cycle Day 1, Predose7.0 ± 2.49.3 ± 4.78.1 ± 7.75.7 ± 5.18.3 ± 2.77.4 ± 4.4
Cycle Day 1, 1 h6.9 ± 4.17.0 ± 3.96.5 ± 3.74.7 ± 4.45.7 ± 3.65.8 ± 3.8
Cycle Day 1, 2 h10.5 ± 6.58.3 ± 3.56.5 ± 5.67.6 ± 3.73.2 ± 7.24.2 ± 4.6
Cycle Day 1, 4 h9.1 ± 3.66.6 ± 7.84.9 ± 4.35.1 ± 3.16.2 ± 2.76.9 ± 5.5
Cycle Day 1, 8 h9.1 ± 7.16.0 ± 5.57.9 ± 5.25.5 ± 3.44.7 ± 7.67.0 ± 5.0
Cycle Day 1, 12 h8.6 ± 7.77.9 ± 3.95.5 ± 6.29.3 ± 6.36.6 ± 2.56.2 ± 4.3
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 4-Hour Averages of Systolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0-4 hrs: Time Matched Baseline125.67 ± 10.39125.67 ± 10.39125.67 ± 10.39125.72 ± 11.02125.72 ± 11.02
0-4 hrs: Cycle Day 2 Change-5.18 ± 5.70-10.57 ± 8.67-8.98 ± 9.08-11.57 ± 11.00-13.15 ± 12.59
4-8 hrs: Time Matched Baseline124.28 ± 8.07124.28 ± 8.07124.28 ± 8.07123.32 ± 7.94123.32 ± 7.94
4-8 hrs: Cycle Day 2 Change-5.56 ± 10.61-9.45 ± 9.68-9.03 ± 12.55-13.26 ± 11.78-14.18 ± 10.07
8-12 hrs: Time Matched Baseline128.95 ± 9.99128.95 ± 9.99128.95 ± 9.99127.42 ± 9.26127.42 ± 9.26
8-12 hrs: Cycle Day 2 Change-2.65 ± 12.85-8.80 ± 14.91-6.81 ± 10.27-10.51 ± 12.34-11.93 ± 13.47
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Systolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0.5 hr: Time Matched Baseline140.30 ± 18.66140.30 ± 18.66140.30 ± 18.66138.22 ± 18.53138.22 ± 18.53
0.5 hr: Cycle Day 2 Change-4.90 ± 6.89-14.80 ± 8.78-10.10 ± 10.09-11.67 ± 13.06-10.67 ± 9.95
1 hr: Time Matched Baseline128.60 ± 12.56128.60 ± 12.56128.60 ± 12.56128.89 ± 13.29128.89 ± 13.29
1 hr: Cycle Day 2 Change-7.70 ± 12.36-12.50 ± 14.00-10.80 ± 16.19-8.56 ± 17.41-14.22 ± 15.74
1.5 hrs: Time Matched Baseline125.10 ± 13.99125.10 ± 13.99125.10 ± 13.99125.67 ± 14.71125.67 ± 14.71
1.5 hrs: Cycle Day 2 Change-5.00 ± 11.75-9.10 ± 18.46-10.40 ± 14.39-14.33 ± 12.71-13.67 ± 16.81
2 hrs: Time Matched Baseline122.70 ± 10.68122.70 ± 10.68122.70 ± 10.68123.22 ± 11.19123.22 ± 11.19
2 hrs: Cycle Day 2 Change-5.10 ± 14.42-6.30 ± 10.56-8.90 ± 9.92-12.56 ± 13.25-13.11 ± 16.32
2.5 hrs: Time Matched Baseline120.20 ± 6.05120.20 ± 6.05120.20 ± 6.05120.22 ± 6.42120.22 ± 6.42
2.5 hrs: Cycle Day 2 Change0 ± 13.55-10.10 ± 12.56-7.40 ± 12.81-13.11 ± 13.16-12.33 ± 12.11
3 hrs: Time Matched Baseline119.10 ± 13.04119.10 ± 13.04119.10 ± 13.04118.78 ± 13.79118.78 ± 13.79
3 hrs: Cycle Day 2 Change-3.20 ± 16.29-6.40 ± 19.78-4.70 ± 17.61-8.22 ± 18.77-11.56 ± 18.42
3.5 hrs: Time Matched Baseline120.89 ± 13.77120.89 ± 13.77120.89 ± 13.77120.75 ± 14.71120.75 ± 14.71
3.5 hrs: Cycle Day 2 Change-6.56 ± 15.95-14.11 ± 14.29-10.67 ± 12.36-9.25 ± 19.03-12.88 ± 22.40
4 hrs: Time Matched Baseline126.30 ± 12.57126.30 ± 12.57123.78 ± 10.31127.56 ± 12.65127.56 ± 12.65
4 hrs: Cycle Day 2 Change-8.00 ± 8.94-11.30 ± 12.70-5.56 ± 13.31-13.78 ± 12.66-15.33 ± 18.41
4.5 hrs: Time Matched Baseline129.80 ± 13.60129.80 ± 13.60129.80 ± 13.60127.33 ± 11.82127.33 ± 11.82
4.5 hrs: Cycle Day 2 Change-10.70 ± 11.98-10.50 ± 14.69-14.70 ± 10.71-8.78 ± 11.20-13.44 ± 17.40
5 hrs: Time Matched Baseline120.80 ± 14.44120.80 ± 14.44120.80 ± 14.44119.56 ± 14.73119.56 ± 14.73
5 hrs: Cycle Day 2 Change-1.90 ± 13.89-6.20 ± 14.54-5.20 ± 19.86-7.33 ± 17.33-11.67 ± 17.43
5.5 hrs: Time Matched Baseline123.50 ± 16.18123.50 ± 16.18123.50 ± 16.18123.33 ± 17.15123.33 ± 17.15
5.5 hrs: Cycle Day 2 Change-3.10 ± 15.74-9.40 ± 14.95-9.20 ± 14.90-18.11 ± 19.66-17.44 ± 20.73
6 hrs: Time Matched Baseline122.00 ± 11.27124.89 ± 7.01122.00 ± 11.27120.78 ± 11.23120.78 ± 11.23
6 hrs: Cycle Day 2 Change-6.90 ± 16.04-12.00 ± 11.86-7.80 ± 13.80-15.33 ± 17.73-16.11 ± 14.48
6.5 hrs: Time Matched Baseline121.40 ± 7.68121.40 ± 7.68121.40 ± 7.68121.44 ± 8.14121.44 ± 8.14
6.5 hrs: Cycle Day 2 Change-2.00 ± 17.95-7.60 ± 15.90-4.60 ± 17.60-12.44 ± 18.41-14.44 ± 13.97
7 hrs: Time Matched Baseline125.50 ± 10.17125.50 ± 10.17125.50 ± 10.17126.22 ± 10.51126.22 ± 10.51
7 hrs: Cycle Day 2 Change-5.50 ± 13.88-11.60 ± 15.28-10.70 ± 16.34-15.44 ± 13.46-13.78 ± 11.36
7.5 hrs: Time Matched Baseline126.30 ± 12.31126.30 ± 12.31126.30 ± 12.31125.44 ± 12.74125.44 ± 12.74
7.5 hrs: Cycle Day 2 Change-8.00 ± 16.80-12.30 ± 17.75-12.30 ± 21.43-16.56 ± 22.57-14.33 ± 20.27
8 hrs: Time Matched Baseline124.90 ± 12.68124.90 ± 12.68124.90 ± 12.68122.44 ± 10.63122.44 ± 10.63
8 hrs: Cycle Day 2 Change-6.40 ± 21.29-9.10 ± 13.54-7.70 ± 19.81-12.11 ± 22.83-12.22 ± 15.70
8.5 hrs: Time Matched Baseline126.10 ± 12.13126.10 ± 12.13125.11 ± 12.43123.89 ± 10.52123.89 ± 10.52
8.5 hrs: Cycle Day 2 Change-5.00 ± 13.32-8.40 ± 17.58-1.33 ± 9.42-12.11 ± 16.97-12.11 ± 17.51
9 hrs: Time Matched Baseline127.20 ± 11.12127.20 ± 11.12127.20 ± 11.12125.67 ± 10.62125.67 ± 10.62
9 hrs: Cycle Day 2 Change-2.60 ± 17.44-7.90 ± 21.66-7.20 ± 18.33-13.78 ± 19.77-15.44 ± 15.16
9.5 hrs: Time Matched Baseline128.30 ± 14.38128.30 ± 14.38128.30 ± 14.38126.78 ± 14.38126.78 ± 14.38
9.5 hrs: Cycle Day 2 Change-1.90 ± 23.19-14.00 ± 22.14-4.70 ± 18.69-12.11 ± 22.79-11.56 ± 19.64
10 hrs: Time Matched Baseline128.56 ± 14.78128.56 ± 14.78128.56 ± 14.78126.50 ± 14.36126.50 ± 14.36
10 hrs: Cycle Day 2 Change-2.78 ± 20.11-10.67 ± 19.54-5.44 ± 13.42-9.63 ± 22.49-4.25 ± 24.81
10.5 hrs: Time Matched Baseline136.90 ± 19.17137.89 ± 20.07136.90 ± 19.17133.33 ± 16.45133.33 ± 16.45
10.5 hrs: Cycle Day 2 Change-5.20 ± 22.09-5.78 ± 18.03-8.10 ± 16.13-11.33 ± 11.96-11.78 ± 16.28
11 hrs: Time Matched Baseline133.44 ± 14.97133.70 ± 14.13133.44 ± 14.97133.11 ± 14.86133.11 ± 14.86
11 hrs: Cycle Day 2 Change-3.00 ± 16.05-15.50 ± 11.64-12.56 ± 9.17-15.78 ± 16.54-19.00 ± 21.04
11.5 hrs: Time Matched Baseline126.30 ± 10.04126.30 ± 10.04126.30 ± 10.04126.11 ± 10.64126.11 ± 10.64
11.5 hrs: Cycle Day 2 Change-3.20 ± 8.40-3.20 ± 12.93-8.70 ± 6.06-4.56 ± 8.26-12.22 ± 14.01
12 hrs: Time Matched Baseline124.05 ± 9.42124.05 ± 9.42124.05 ± 9.42123.17 ± 9.55123.17 ± 9.55
12 hrs: Cycle Day 2 Change3.45 ± 9.54-4.10 ± 13.33-2.55 ± 10.93-4.94 ± 7.27-6.72 ± 14.85
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline126.27 ± 8.62126.27 ± 8.62126.27 ± 8.62125.45 ± 8.72125.45 ± 8.72
Cycle Day 2 Change-4.42 ± 8.59-9.55 ± 9.98-8.22 ± 9.74-11.74 ± 10.71-13.05 ± 10.66
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Diastolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0-4 hrs: Time Matched Baseline75.59 ± 6.0575.59 ± 6.0575.59 ± 6.0574.94 ± 6.0474.94 ± 6.04
0-4 hrs: Cycle Day 2 Change-2.96 ± 3.75-7.59 ± 6.04-5.96 ± 5.53-7.94 ± 4.75-8.32 ± 6.28
4-8 hrs: Time Matched Baseline74.54 ± 7.5474.54 ± 7.5474.54 ± 7.5472.88 ± 5.7472.88 ± 5.74
4-8 hrs: Cycle Day 2 Change-2.28 ± 7.46-4.03 ± 6.37-3.49 ± 8.91-7.61 ± 5.88-5.92 ± 7.12
8-12 hrs: Time Matched Baseline77.05 ± 6.3177.05 ± 6.3177.05 ± 6.3175.75 ± 5.0875.75 ± 5.08
8-12 hrs: Cycle Day 2 Change1.41 ± 5.71-3.70 ± 5.89-1.45 ± 4.79-4.63 ± 4.92-4.84 ± 6.78
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Diastolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0.5 hr: Time Matched Baseline87.90 ± 7.4587.90 ± 7.4587.90 ± 7.4586.44 ± 6.2186.44 ± 6.21
0.5 hr: Cycle Day 2 Change-2.40 ± 6.04-8.70 ± 11.37-2.60 ± 6.50-7.56 ± 6.48-7.44 ± 9.81
1 hr: Time Matched Baseline77.90 ± 8.5877.90 ± 8.5877.90 ± 8.5877.11 ± 8.7177.11 ± 8.71
1 hr: Cycle Day 2 Change-2.70 ± 7.29-10.40 ± 5.38-6.30 ± 10.63-7.56 ± 6.11-11.33 ± 8.08
1.5 hrs: Time Matched Baselline73.70 ± 11.0273.70 ± 11.0273.70 ± 11.0272.89 ± 11.3672.89 ± 11.36
1.5 hrs: Cycle Day 2 Change-4.70 ± 11.54-6.30 ± 17.63-9.20 ± 10.61-9.78 ± 12.36-10.11 ± 10.76
2 hrs: Time Matched Baseline72.30 ± 7.5972.30 ± 7.5972.30 ± 7.5971.00 ± 6.7671.00 ± 6.76
2 hrs: Cycle Day 2 Change-3.10 ± 8.54-5.60 ± 10.41-7.40 ± 8.37-5.33 ± 10.99-7.89 ± 9.40
2.5 hrs: Time Matched Baseline72.20 ± 7.9372.20 ± 7.9372.20 ± 7.9371.89 ± 8.3471.89 ± 8.34
2.5 hrs: Cycle Day 2 Change-3.10 ± 12.91-9.70 ± 14.30-5.80 ± 11.59-11.11 ± 8.91-6.22 ± 9.90
3 hrs: Time Matched Baseline73.50 ± 11.8373.50 ± 11.8373.50 ± 11.8373.44 ± 12.5573.44 ± 12.55
3 hrs: Cycle Day 2 Change-5.00 ± 9.82-7.90 ± 15.67-8.50 ± 14.18-8.44 ± 9.62-7.78 ± 17.50
3.5 hrs: Time Matched Baseline70.33 ± 9.7070.33 ± 9.7070.33 ± 9.7069.50 ± 10.0169.50 ± 10.01
3.5 hrs: Cycle Day 2 Change-1.67 ± 12.57-6.89 ± 11.04-3.78 ± 9.19-8.00 ± 11.83-5.88 ± 13.89
4 hrs: Time Matched Baseline76.60 ± 6.0276.60 ± 6.0276.33 ± 6.3276.89 ± 6.3176.89 ± 6.31
4 hrs: Cycle Day 2 Change-1.90 ± 6.40-6.10 ± 6.08-2.22 ± 11.02-6.56 ± 9.58-9.67 ± 9.71
4.5 hrs: Time Matched Baseline79.40 ± 12.8879.40 ± 12.8879.40 ± 12.8876.56 ± 9.7776.56 ± 9.77
4.5 hrs: Cycle Day 2 Change-1.60 ± 11.72-5.80 ± 11.11-7.30 ± 9.78-3.78 ± 7.29-6.44 ± 7.84
5 hrs: Time Matched Baseline70.10 ± 14.1070.10 ± 14.1070.10 ± 14.1067.78 ± 12.7667.78 ± 12.76
5 hrs: Cycle Day 2 Change-1.20 ± 14.651.70 ± 14.24-0.70 ± 13.490.11 ± 14.17-0.67 ± 14.49
5.5 hrs: Time Matched Baseline75.30 ± 7.5475.30 ± 7.5475.30 ± 7.5474.22 ± 7.1474.22 ± 7.14
5.5 hrs: Cycle Day 2 Change-3.30 ± 9.19-6.00 ± 8.88-5.00 ± 7.62-14.67 ± 10.85-9.33 ± 9.63
6 hrs: Time Matched Baseline74.80 ± 7.6775.89 ± 7.2774.80 ± 7.6773.44 ± 6.7573.44 ± 6.75
6 hrs: Cycle Day 2 Change-5.70 ± 16.38-7.44 ± 9.86-6.10 ± 10.87-15.22 ± 10.72-8.11 ± 10.45
6.5 hrs: Time Matched Baseline73.60 ± 7.1773.60 ± 7.1773.60 ± 7.1772.67 ± 6.9372.67 ± 6.93
6.5 hrs: Cycle Day 2 Change-3.70 ± 12.28-5.30 ± 6.86-3.20 ± 14.86-8.00 ± 10.81-8.78 ± 12.34
7 hrs: Time Matched Baseline75.70 ± 7.7675.70 ± 7.7675.70 ± 7.7674.67 ± 7.4774.67 ± 7.47
7 hrs: Cycle Day 2 Change-1.50 ± 10.56-5.60 ± 10.39-1.70 ± 12.46-11.22 ± 10.11-4.78 ± 11.98
7.5 hrs: Time Matched Baseline73.70 ± 12.2973.70 ± 12.2973.70 ± 12.2971.89 ± 11.5471.89 ± 11.54
7.5 hrs: Cycle Day 2 Change-0.80 ± 12.65-3.50 ± 14.73-3.20 ± 16.51-2.78 ± 15.71-4.11 ± 20.57
8 hrs: Time Matched Baseline73.70 ± 13.2873.70 ± 13.2873.70 ± 13.2871.78 ± 12.5271.78 ± 12.52
8 hrs: Cycle Day 2 Change-0.40 ± 15.46-1.80 ± 12.93-0.70 ± 13.56-5.33 ± 17.05-5.11 ± 18.45
8.5 hrs: Time Matched Baseline73.70 ± 9.2673.70 ± 9.2673.33 ± 9.7571.33 ± 5.7971.33 ± 5.79
8.5 hrs: Cycle Day 2 Change2.20 ± 9.85-3.60 ± 7.600.89 ± 10.48-2.67 ± 10.23-2.78 ± 11.22
9 hrs: Time Matched Baseline75.90 ± 10.3475.90 ± 10.3475.90 ± 10.3474.22 ± 9.4274.22 ± 9.42
9 hrs: Cycle Day 2 Change3.80 ± 11.51-0.90 ± 13.92-0.80 ± 12.86-6.67 ± 12.74-6.67 ± 12.13
9.5 hrs: Time Matched Baseline80.90 ± 10.2880.90 ± 10.2880.90 ± 10.2880.00 ± 10.4880.00 ± 10.48
9.5 hrs: Cycle Day 2 Change0.60 ± 13.48-12.20 ± 11.63-3.60 ± 15.04-9.78 ± 11.38-7.11 ± 13.36
10 hrs: Time Matched Baseline79.56 ± 7.3279.56 ± 7.3279.56 ± 7.3278.63 ± 7.2378.63 ± 7.23
10 hrs: Cycle Day 2 Change0.56 ± 10.45-3.67 ± 9.68-1.78 ± 4.66-7.75 ± 13.04-3.75 ± 12.69
10.5 hrs: Time Matched Baseline83.60 ± 10.2484.22 ± 10.6683.60 ± 10.2482.56 ± 10.2882.56 ± 10.28
10.5 hrs: Cycle Day 2 Change-2.80 ± 9.38-4.56 ± 9.15-1.60 ± 4.88-8.11 ± 11.24-9.22 ± 10.10
11 hrs: Time Matched Baseline76.22 ± 8.4577.00 ± 8.3476.22 ± 8.4575.89 ± 8.0275.89 ± 8.02
11 hrs: Cycle Day 2 Change0.89 ± 10.56-5.40 ± 7.85-5.56 ± 8.00-6.44 ± 9.94-8.22 ± 12.08
11.5 hrs: Time Matched Baseline73.50 ± 9.9673.50 ± 9.9673.50 ± 9.9672.78 ± 10.2872.78 ± 10.28
11.5 hrs: Cycle Day 2 Change0.20 ± 9.50-0.50 ± 11.65-2.80 ± 8.070.78 ± 10.37-2.78 ± 10.29
12 hrs: Time Matched Baseline73.20 ± 6.4473.20 ± 6.4473.20 ± 6.4471.56 ± 4.0371.56 ± 4.03
12 hrs: Cycle Day 2 Change5.30 ± 8.21-0.10 ± 5.572.50 ± 12.061.89 ± 9.490.89 ± 8.37
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Diastolic Blood Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline75.71 ± 6.2775.71 ± 6.2775.71 ± 6.2774.51 ± 5.2874.51 ± 5.28
Cycle Day 2 Change-1.26 ± 4.08-5.10 ± 4.67-3.59 ± 5.72-6.71 ± 4.38-6.34 ± 5.84
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Mean Arterial Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0-4 hrs: Time Matched Baseline92.61 ± 6.2392.61 ± 6.2392.61 ± 6.2392.21 ± 6.4792.21 ± 6.47
0-4 hrs: Cycle Day 2 Change-3.93 ± 3.38-8.93 ± 6.29-7.64 ± 6.16-9.13 ± 6.21-9.67 ± 8.37
4-8 hrs: Time Matched Baseline91.38 ± 6.4991.38 ± 6.4991.38 ± 6.4989.99 ± 5.0689.99 ± 5.06
4-8 hrs: Cycle Day 2 Change-3.50 ± 7.59-5.80 ± 6.58-5.55 ± 9.34-10.29 ± 6.73-8.65 ± 6.93
8-12 hrs: Time Matched Baseline93.99 ± 6.3893.99 ± 6.3893.99 ± 6.3892.51 ± 4.6392.51 ± 4.63
8-12 hrs: Cycle Day 2 Change0.36 ± 8.87-4.34 ± 7.72-3.00 ± 6.44-6.81 ± 5.80-6.58 ± 8.05
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Mean Arterial Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0.5 hr: Time Matched Baseline104.50 ± 9.96104.50 ± 9.96104.50 ± 9.96102.00 ± 6.42102.00 ± 6.42
0.5 hr: Cycle Day 2 Change-3.70 ± 7.21-9.20 ± 10.99-3.90 ± 8.50-5.33 ± 6.06-4.11 ± 10.41
1 hr: Time Matched Baseline96.80 ± 7.7396.80 ± 7.7396.80 ± 7.7396.33 ± 8.0596.33 ± 8.05
1 hr: Cycle Day 2 Change-7.00 ± 7.73-12.70 ± 6.80-10.60 ± 11.05-10.11 ± 9.24-14.89 ± 9.31
1.5 hrs: Time Matched Baseline91.30 ± 13.0291.30 ± 13.0291.30 ± 13.0291.22 ± 13.8191.22 ± 13.81
1.5 hrs: Cycle Day 2 Change-5.20 ± 11.39-8.80 ± 17.82-10.00 ± 11.55-11.67 ± 14.97-12.00 ± 15.28
2 hrs: Time Matched Baseline89.20 ± 6.5889.20 ± 6.5889.20 ± 6.5888.44 ± 6.5088.44 ± 6.50
2 hrs: Cycle Day 2 Change-1.70 ± 11.16-6.10 ± 8.92-9.10 ± 8.52-8.11 ± 10.17-8.67 ± 16.51
2.5 hrs: Time Matched Baseline88.80 ± 6.7088.80 ± 6.7088.80 ± 6.7088.67 ± 7.0988.67 ± 7.09
2.5 hrs: Cycle Day 2 Change-2.40 ± 12.75-11.40 ± 15.25-7.20 ± 10.94-12.22 ± 9.86-10.11 ± 9.83
3 hrs: Time Matched Baseline88.10 ± 11.2488.10 ± 11.2488.10 ± 11.2488.22 ± 11.9188.22 ± 11.91
3 hrs: Cycle Day 2 Change-4.20 ± 10.54-6.90 ± 14.26-5.50 ± 15.17-8.78 ± 9.43-7.44 ± 17.26
3.5 hrs: Time Matched Baseline87.44 ± 10.0887.44 ± 10.0887.44 ± 10.0887.25 ± 10.7587.25 ± 10.75
3.5 hrs: Cycle Day 2 Change-3.89 ± 13.40-9.00 ± 11.24-6.56 ± 8.80-8.63 ± 13.16-7.50 ± 15.68
4 hrs: Time Matched Baseline94.10 ± 7.3494.10 ± 7.3492.78 ± 6.4094.78 ± 7.4594.78 ± 7.45
4 hrs: Cycle Day 2 Change-4.00 ± 8.46-7.90 ± 7.29-5.78 ± 10.33-8.78 ± 9.02-12.11 ± 13.60
4.5 hrs: Time Matched Baseline97.30 ± 10.9297.30 ± 10.9297.30 ± 10.9294.67 ± 7.5094.67 ± 7.50
4.5 hrs: Cycle Day 2 Change-4.30 ± 7.75-7.40 ± 10.16-11.30 ± 8.14-5.89 ± 2.93-9.67 ± 7.94
5 hrs: Time Matched Baseline86.60 ± 12.4786.60 ± 12.4786.60 ± 12.4784.56 ± 11.3084.56 ± 11.30
5 hrs: Cycle Day 2 Change-1.30 ± 14.03-0.80 ± 11.52-2.80 ± 15.51-3.00 ± 12.61-5.11 ± 12.29
5.5 hrs: Time Matched Baseline92.00 ± 7.2192.00 ± 7.2192.00 ± 7.2191.11 ± 7.0491.11 ± 7.04
5.5 hrs: Cycle Day 2 Change-3.40 ± 10.95-8.70 ± 8.38-7.10 ± 8.12-18.44 ± 10.03-13.33 ± 11.09
6 hrs: Time Matched Baseline90.70 ± 7.1892.33 ± 5.2990.70 ± 7.1889.78 ± 6.9689.78 ± 6.96
6 hrs: Cycle Day 2 Change-5.80 ± 14.99-9.00 ± 9.54-7.20 ± 11.06-15.56 ± 10.50-10.67 ± 11.15
6.5 hrs: Time Matched Baseline89.80 ± 6.4189.80 ± 6.4189.80 ± 6.4189.44 ± 6.6989.44 ± 6.69
6.5 hrs: Cycle Day 2 Change-3.50 ± 12.09-6.10 ± 9.18-4.40 ± 12.82-11.44 ± 11.07-11.33 ± 10.63
7 hrs: Time Matched Baseline92.90 ± 7.9292.90 ± 7.9292.90 ± 7.9292.44 ± 8.2692.44 ± 8.26
7 hrs: Cycle Day 2 Change-3.90 ± 12.06-8.50 ± 12.43-5.60 ± 12.73-14.11 ± 10.81-6.44 ± 11.67
7.5 hrs: Time Matched Baseline90.50 ± 11.7290.50 ± 11.7290.50 ± 11.7288.78 ± 11.0188.78 ± 11.01
7.5 hrs: Cycle Day 2 Change-2.70 ± 15.60-3.90 ± 15.15-3.70 ± 17.84-6.33 ± 16.67-5.44 ± 18.26
8 hrs: Time Matched Baseline91.20 ± 13.0091.20 ± 13.0091.20 ± 13.0089.11 ± 11.8889.11 ± 11.88
8 hrs: Cycle Day 2 Change-3.10 ± 17.12-3.90 ± 12.57-2.30 ± 15.82-7.56 ± 17.98-7.22 ± 13.63
8.5 hrs: Time Matched Baseline91.80 ± 10.0891.80 ± 10.0891.00 ± 10.3489.44 ± 7.2089.44 ± 7.20
8.5 hrs: Cycle Day 2 Change-0.80 ± 11.21-6.30 ± 9.26-0.89 ± 10.29-6.11 ± 12.73-6.33 ± 11.28
9 hrs: Time Matched Baseline92.00 ± 8.5092.00 ± 8.5092.00 ± 8.5090.44 ± 7.3590.44 ± 7.35
9 hrs: Cycle Day 2 Change3.30 ± 12.00-1.80 ± 14.61-1.30 ± 14.25-7.44 ± 12.41-8.11 ± 11.26
9.5 hrs: Time Matched Baseline96.40 ± 11.7596.40 ± 11.7596.40 ± 11.7595.22 ± 11.8295.22 ± 11.82
9.5 hrs: Cycle Day 2 Change1.50 ± 20.74-11.90 ± 14.81-3.40 ± 16.81-11.11 ± 15.32-8.22 ± 16.05
10 hrs: Time Matched Baseline95.11 ± 9.6895.11 ± 9.6895.11 ± 9.6893.63 ± 9.1893.63 ± 9.18
10 hrs: Cycle Day 2 Change-0.44 ± 14.79-4.89 ± 10.73-2.56 ± 7.99-9.75 ± 14.32-2.50 ± 18.24
10.5 hrs: Time Matched Baseline101.00 ± 10.84101.78 ± 11.20101.00 ± 10.8498.89 ± 9.0698.89 ± 9.06
10.5 hrs: Cycle Day 2 Change-2.70 ± 13.15-3.67 ± 10.95-3.50 ± 6.52-10.11 ± 7.69-10.67 ± 11.45
11 hrs: Time Matched Baseline95.00 ± 10.2895.50 ± 9.8295.00 ± 10.2894.33 ± 9.6694.33 ± 9.66
11 hrs: Cycle Day 2 Change-0.56 ± 11.17-7.10 ± 11.26-8.22 ± 9.92-10.00 ± 14.24-11.78 ± 14.70
11.5 hrs: Time Matched Baseline90.10 ± 8.4590.10 ± 8.4590.10 ± 8.4589.56 ± 8.7889.56 ± 8.78
11.5 hrs: Cycle Day 2 Change-1.40 ± 7.660.60 ± 10.62-5.20 ± 5.39-0.78 ± 8.35-3.89 ± 7.46
12 hrs: Time Matched Baseline90.45 ± 6.3090.45 ± 6.3090.45 ± 6.3088.94 ± 4.3788.94 ± 4.37
12 hrs: Cycle Day 2 Change3.80 ± 7.63-0.25 ± 7.670.95 ± 10.96-0.72 ± 6.64-0.89 ± 7.88
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Mean Arterial Pressure
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline92.64 ± 5.7792.64 ± 5.7792.64 ± 5.7791.55 ± 4.9091.55 ± 4.90
Cycle Day 2 Change-2.33 ± 5.21-6.33 ± 5.44-5.34 ± 6.58-8.72 ± 5.43-8.28 ± 6.54
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0-4 hrs, 4-8 hrs, 8-12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 4-Hour Averages of Pulse
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0-4 hrs: Time Matched Baseline75.61 ± 12.3775.61 ± 12.3775.61 ± 12.3776.59 ± 12.7076.59 ± 12.70
0-4 hrs: Cycle Day 2 Change2.49 ± 3.626.11 ± 4.498.91 ± 7.607.10 ± 4.437.38 ± 6.58
4-8 hrs: Time Matched Baseline73.24 ± 11.1973.24 ± 11.1973.24 ± 11.1973.81 ± 11.7273.81 ± 11.72
4-8 hrs: Cycle Day 2 Change9.24 ± 5.307.56 ± 6.516.50 ± 7.8212.82 ± 7.168.89 ± 8.83
8-12 hrs: Time Matched Baseline76.22 ± 12.5976.22 ± 12.5976.22 ± 12.5976.95 ± 13.1376.95 ± 13.13
8-12 hrs: Cycle Day 2 Change1.91 ± 7.04-1.20 ± 6.521.51 ± 5.342.53 ± 5.553.35 ± 8.48
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2: 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, 10 hrs, 10.5 hrs, 11 hrs, 11.5 hrs, 12 hrs
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM 30 Minute Averages of Pulse
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
0.5 hr: Time Matched Baseline76.30 ± 9.8976.30 ± 9.8976.30 ± 9.8975.67 ± 10.2775.67 ± 10.27
0.5 hr: Cycle Day 2 Change-0.60 ± 4.171.60 ± 5.231.50 ± 8.342.67 ± 9.622.11 ± 5.42
1 hr: Time Matched Baseline73.50 ± 11.6973.50 ± 11.6973.50 ± 11.6974.44 ± 11.9974.44 ± 11.99
1 hr: Cycle Day 2 Change3.00 ± 6.097.30 ± 8.1911.00 ± 10.098.11 ± 7.859.89 ± 9.98
1.5 hrs: Time Matched Baseline74.80 ± 12.2574.80 ± 12.2574.80 ± 12.2575.56 ± 12.7475.56 ± 12.74
1.5 hrs: Cycle Day 2 Change5.60 ± 4.9318.90 ± 12.7214.60 ± 14.2110.44 ± 7.7514.44 ± 5.39
2 hrs: Time Matched Baseline78.80 ± 15.3078.80 ± 15.3078.80 ± 15.3080.22 ± 15.5180.22 ± 15.51
2 hrs: Cycle Day 2 Change0.90 ± 8.137.40 ± 5.916.90 ± 7.0314.00 ± 22.925.33 ± 9.50
2.5 hrs: Time Matched Baseline76.60 ± 13.4376.60 ± 13.4376.60 ± 13.4377.89 ± 13.5777.89 ± 13.57
2.5 hrs: Cycle Day 2 Change3.20 ± 7.795.20 ± 6.719.30 ± 12.288.44 ± 7.706.67 ± 11.70
3 hrs: Time Matched Baseline77.10 ± 15.5377.10 ± 15.5377.10 ± 15.5378.56 ± 15.7378.56 ± 15.73
3 hrs: Cycle Day 2 Change2.70 ± 9.011.20 ± 10.8112.10 ± 14.562.22 ± 8.777.89 ± 12.23
3.5 hrs: Time Matched Baseline74.33 ± 15.8474.33 ± 15.8474.33 ± 15.8475.75 ± 16.3175.75 ± 16.31
3.5 hrs: Cycle Day 2 Change2.78 ± 6.852.44 ± 5.178.33 ± 10.105.13 ± 10.525.13 ± 13.82
4 hrs: Time Matched Baseline73.70 ± 15.9873.70 ± 15.9874.67 ± 16.6475.11 ± 16.2775.11 ± 16.27
4 hrs: Cycle Day 2 Change2.70 ± 6.633.90 ± 9.458.89 ± 13.595.78 ± 8.767.44 ± 13.53
4.5 hrs: Time Matched Baseline80.80 ± 13.7380.80 ± 13.7380.80 ± 13.7381.56 ± 14.3481.56 ± 14.34
4.5 hrs: Cycle Day 2 Change4.70 ± 7.022.70 ± 8.039.60 ± 15.2410.56 ± 10.867.33 ± 9.64
5 hrs: Time Matched Baseline75.50 ± 10.2175.50 ± 10.2175.50 ± 10.2176.44 ± 10.3676.44 ± 10.36
5 hrs: Cycle Day 2 Change5.50 ± 11.457.90 ± 13.874.00 ± 10.6517.78 ± 14.817.00 ± 15.26
5.5 hrs: Time Matched Baseline75.50 ± 10.1075.50 ± 10.1075.50 ± 10.1076.11 ± 10.5276.11 ± 10.52
5.5 hrs: Cycle Day 2 Change7.80 ± 11.695.70 ± 11.796.80 ± 11.1210.00 ± 11.225.00 ± 13.22
6 hrs: Time Matched Baseline72.00 ± 11.1171.44 ± 11.6372.00 ± 11.1172.22 ± 11.7672.22 ± 11.76
6 hrs: Cycle Day 2 Change12.60 ± 15.077.89 ± 9.577.40 ± 10.3616.00 ± 13.878.56 ± 8.79
6.5 hrs: Time Matched Baseline71.40 ± 11.0471.40 ± 11.0471.40 ± 11.0471.56 ± 11.7071.56 ± 11.70
6.5 hrs: Cycle Day 2 Change13.10 ± 7.5310.30 ± 10.478.30 ± 11.7313.44 ± 10.5713.00 ± 15.73
7 hrs: Time Matched Baseline69.10 ± 13.4769.10 ± 13.4769.10 ± 13.4769.56 ± 14.2069.56 ± 14.20
7 hrs: Cycle Day 2 Change14.00 ± 6.3914.20 ± 14.208.30 ± 7.0412.56 ± 4.4213.00 ± 9.75
7.5 hrs: Time Matched Baseline70.40 ± 14.4270.40 ± 14.4270.40 ± 14.4270.56 ± 15.2870.56 ± 15.28
7.5 hrs: Cycle Day 2 Change9.70 ± 9.236.40 ± 8.765.70 ± 7.2412.78 ± 9.7611.67 ± 14.98
8 hrs: Time Matched Baseline71.20 ± 13.7271.20 ± 13.7271.20 ± 13.7272.44 ± 13.9472.44 ± 13.94
8 hrs: Cycle Day 2 Change6.50 ± 7.043.70 ± 5.141.90 ± 6.579.44 ± 8.115.56 ± 8.71
8.5 hrs: Time Matched Baseline70.40 ± 13.6370.40 ± 13.6371.33 ± 14.1271.22 ± 14.1971.22 ± 14.19
8.5 hrs: Cycle Day 2 Change5.80 ± 9.613.60 ± 7.181.33 ± 8.446.33 ± 7.928.78 ± 10.35
9 hrs: Time Matched Baseline71.30 ± 15.1071.30 ± 15.1071.30 ± 15.1071.89 ± 15.8971.89 ± 15.89
9 hrs: Cycle Day 2 Change5.30 ± 12.451.50 ± 9.651.60 ± 10.272.22 ± 13.894.44 ± 11.26
9.5 hrs: Time Matched Baseline72.00 ± 14.8372.00 ± 14.8372.00 ± 14.8372.67 ± 15.5772.67 ± 15.57
9.5 hrs: Cycle Day 2 Change3.60 ± 9.380.80 ± 9.203.60 ± 12.336.22 ± 7.518.78 ± 10.17
10 hrs: Time Matched Baseline73.56 ± 12.8273.56 ± 12.8273.56 ± 12.8274.13 ± 13.5874.13 ± 13.58
10 hrs: Cycle Day 2 Change4.89 ± 12.201.56 ± 8.003.11 ± 5.887.88 ± 9.605.75 ± 12.13
10.5 hrs: Time Matched Baseline81.00 ± 12.1281.78 ± 12.5981.00 ± 12.1281.33 ± 12.8181.33 ± 12.81
10.5 hrs: Cycle Day 2 Change0.60 ± 10.84-3.89 ± 10.17-1.00 ± 5.773.11 ± 11.192.11 ± 9.51
11 hrs: Time Matched Baseline82.22 ± 17.1081.30 ± 16.3882.22 ± 17.1082.56 ± 16.8682.56 ± 16.86
11 hrs: Cycle Day 2 Change-4.33 ± 14.96-7.30 ± 14.62-2.67 ± 12.47-2.22 ± 15.21-3.56 ± 7.49
11.5 hrs: Time Matched Baseline81.60 ± 15.9081.60 ± 15.9081.60 ± 15.9082.78 ± 16.4082.78 ± 16.40
11.5 hrs: Cycle Day 2 Change-3.10 ± 8.70-5.80 ± 11.280.20 ± 9.44-4.89 ± 9.52-3.56 ± 13.42
12 hrs: Time Matched Baseline78.45 ± 12.1678.45 ± 12.1678.45 ± 12.1678.94 ± 12.7978.94 ± 12.79
12 hrs: Cycle Day 2 Change2.25 ± 12.760.65 ± 9.604.40 ± 7.172.44 ± 6.942.78 ± 10.60
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2). Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle); Cycle Day 2
Reported as:
Mean · mmHg
Change From Time-Matched Baseline (Placebo Cycle) Over Time in ABPM Daytime (12-Hour) Averages of Pulse
mmHg10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline75.01 ± 11.9575.01 ± 11.9575.01 ± 11.9575.78 ± 12.4275.78 ± 12.42
Cycle Day 2 Change4.55 ± 4.434.14 ± 4.805.70 ± 6.227.49 ± 3.886.55 ± 7.30
PrimaryChange From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse
Time frame:
Follow-up Visit Day 32 (± 2 days)
Reported as:
Mean · bpm
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse
bpmAll Participants
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Pulse-2.5 ± 5.4
PrimaryChange From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure
Time frame:
Follow-up Visit Day 32 (± 2 days)
Reported as:
Mean · mmHg
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure
mmHgAll Participants
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Systolic Blood Pressure3.5 ± 7.3
PrimaryChange From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure
Time frame:
Follow-up Visit Day 32 (± 2 days)
Reported as:
Mean · mmHg
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure
mmHgAll Participants
Change From Pre- to Post-Nitroglycerin Dose Assessment in Supine Diastolic Blood Pressure-0.5 ± 3.8
PrimaryChange From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)

Study baseline is defined as the Day -1 assessment. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

Time frame:
Study Baseline; Cycle Day 3: 0 h, 4 h, 12 h
Reported as:
Mean · units on a scale
Change From Study Baseline Over Time in Endothelial Function: Reactive Hyperemia Index (RHI)
units on a scaleControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Study Baseline2.21 ± 0.622.21 ± 0.622.28 ± 0.612.21 ± 0.662.28 ± 0.662.28 ± 0.66
Change at Cycle Day 3, 0 h-0.08 ± 0.74-0.14 ± 0.91-0.13 ± 0.690.31 ± 1.080.20 ± 0.87-0.09 ± 0.87
Change at Cycle Day 3, 4 h-0.39 ± 0.650.08 ± 0.990.01 ± 0.75-0.15 ± 0.80-0.17 ± 0.98-0.06 ± 0.78
Change at Cycle Day 3, 12 h-0.03 ± 0.640.33 ± 1.070.29 ± 0.680.07 ± 0.910.17 ± 1.060.37 ± 1.14
PrimaryChange From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle. Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction. Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-matched Baseline (Placebo Cycle); Cycle Day 3: 0 h, 4 h, 12 h
Reported as:
Mean · units on a scale
Change From Time-Matched Baseline (Placebo Cycle) Over Time in Endothelial Function: RHI
units on a scale10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline, 0 h2.13 ± 0.572.15 ± 0.602.24 ± 0.492.28 ± 0.502.28 ± 0.50
Change at Cycle Day 3, 0 h-0.07 ± 0.740 ± 0.870.28 ± 0.640.19 ± 0.39-0.09 ± 1.01
Time-Matched Baseline, 4 h1.82 ± 0.261.82 ± 0.261.82 ± 0.271.84 ± 0.271.84 ± 0.27
Change at Cycle Day 3, 4 h0.47 ± 1.020.40 ± 0.500.25 ± 0.600.26 ± 0.670.37 ± 0.75
Time-Matched Baseline, 12 h2.18 ± 0.482.18 ± 0.482.16 ± 0.512.12 ± 0.512.12 ± 0.51
Change at Cycle Day 3, 12 h0.36 ± 0.770.32 ± 0.390.20 ± 0.540.32 ± 0.660.53 ± 0.68
PrimaryChange From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI

Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values \>1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

Time frame:
Follow-up Visit Day 32 (± 2 days)
Reported as:
Mean · units on a scale
Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI
units on a scaleAll Participants
Change From Pre- to Post-Nitroglycerin Dose Assessment in Endothelial Function: RHI-0.05 ± 0.37
PrimaryChange From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation

Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle. Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation. Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data.

Time frame:
Time-Matched Baseline (Placebo Cycle), Cycle Day 1, 0 h, Cycle Day 1, 4 h
Reported as:
Mean · secs
Change From Time-Matched Baseline (Placebo Cycle) in Platelet Function Assessments: Collagen/Epinephrine Time to Aggregation
secs10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
Time-Matched Baseline, 0 h131.8 ± 60.6132.8 ± 63.8115.5 ± 28.7114.8 ± 30.3114.8 ± 30.3
Change at Cycle Day 1, 0 h-21.0 ± 54.6-38.7 ± 46.5-6.8 ± 25.09.9 ± 47.4-4.2 ± 28.8
Time-Matched Baseline, 4 h121.3 ± 35.0121.3 ± 35.0115.0 ± 29.6114.6 ± 31.4114.6 ± 31.4
Change at Cycle Day 1, 4 h-3.8 ± 22.2-15.5 ± 40.2-7.4 ± 23.914.2 ± 42.7-4.0 ± 32.4

Adverse events

Collected over From first dose of study drug through end of trial (Day 46 [±3 days]). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Control0/11 (0%)0/11 (0%)3/11 (27.3%)
10 mg IW-19730/11 (0%)0/11 (0%)3/11 (27.3%)
20 mg IW-19730/11 (0%)0/11 (0%)2/11 (18.2%)
30 mg IW-19730/10 (0%)0/10 (0%)4/10 (40%)
40 mg IW-19730/9 (0%)0/9 (0%)3/9 (33.3%)
50 mg IW-19730/9 (0%)0/9 (0%)2/9 (22.2%)
Most frequent other events
Showing 10 of 17
Most frequent other events
EventControl10 mg IW-197320 mg IW-197330 mg IW-197340 mg IW-197350 mg IW-1973
HeadacheNervous system disorders1/112/110/112/101/92/9
PalpitationsCardiac disorders0/110/110/110/100/91/9
DiarrhoeaGastrointestinal disorders0/110/110/110/101/91/9
NauseaGastrointestinal disorders0/110/110/110/101/90/9
VomitingGastrointestinal disorders0/110/110/110/101/90/9
Hepatic enzyme increasedInvestigations0/110/110/110/100/91/9
HypoglycaemiaMetabolism and nutrition disorders0/111/110/111/101/91/9
DizzinessNervous system disorders0/110/110/111/100/91/9
Orthostatic hypotensionVascular disorders0/110/110/110/101/90/9
ConstipationGastrointestinal disorders1/110/110/111/100/90/9

Baseline characteristics

Age, Continuous
Age, Continuous(years)All Participants
Mean56.6 ± 6.8
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female4
Male7
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Participants
Hispanic or Latino5
Not Hispanic or Latino6
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)All Participants
White6
Black or African American5
Study Baseline: Supine systolic blood pressure
Study Baseline: Supine systolic blood pressure(mmHg)All Participants
Mean136.3 ± 12.9
Study Baseline: Supine diastolic blood pressure
Study Baseline: Supine diastolic blood pressure(mmHg)All Participants
Mean80.4 ± 5.9
Study Baseline: Pulse
Study Baseline: Pulse(beats per minute)All Participants
Mean72.0 ± 15.9
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides
Study Baseline: Cholesterol, Glucose, HDL-C, LDL-C, Triglycerides(mg/dL)All Participants
Cholesterol185.0 ± 44.9
Glucose143.27 ± 34.34
High-density lipoprotein cholesterol (HDL-C)50.27 ± 14.11
Low-density lipoprotein cholesterol (LDL-C)107.45 ± 36.74
Triglycerides137.73 ± 54.23

6 further baseline measures are reported on the registry.

08

Study locations

1 site
  • ICON Early Phase Unit
    San Antonio, Texas 78209, United States
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

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 Sep 2016 to primary completion in Mar 2017, 6 months.

Results were first posted in Apr 2020, 3 years after primary completion. A results delay was requested in Nov 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 6 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
Sep 15, 2016
First posted
Sep 20, 2016
StartActual
Sep 2016
Primary completionActual
Mar 17, 2017
CompletionActual
Mar 17, 2017
Results delay requested
Nov 21, 2018
Results first posted
Apr 16, 2020
Last update
Apr 16, 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 Apr 16, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02906579
Lead sponsor
Cyclerion Therapeutics
Responsible party
Sponsor
First posted
Sep 20, 2016
Start date
Sep 2016
Primary completion
Mar 17, 2017
Completion
Mar 17, 2017
Results posted
Apr 16, 2020
Last update
Apr 16, 2020
View the source record on ClinicalTrials.gov ↗

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