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CompletedNCT03447990Updated Feb 2, 2023Results posted

v4 Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-491

A Phase 1/2 interventional study of MYK-491 and Placebo in Heart Failure With Reduced Ejection Fraction and Dilated Cardiomyopathy, sponsored by Bristol-Myers Squibb. Completed at 17 sites in 7 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-02-02.

Sponsored by Bristol-Myers Squibb · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

The purpose of this Phase 1b/2a study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MYK-491 in patients with stable heart failure.

02

Conditions studied

  • Heart Failure With Reduced Ejection Fraction
  • Dilated Cardiomyopathy
03

In context

Cardiomyopathy, Dilated

258 studies on the registry are indexed under Cardiomyopathy, Dilated; 65 are open to participants now.

This study's enrollment of 52 is above the median of 41 across 145 interventional studies indexed under Cardiomyopathy, Dilated.

Browse Cardiomyopathy, Dilated studies →

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,562 studies on the registry; 118 are open to participants now.

Of its 435 completed or terminated interventional studies of FDA-regulated products, 227 (52%) have results posted.

Browse Bristol-Myers Squibb studies →

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

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Has stable chronic heart failure with reduced ejection fraction
  • Has adequate acoustic windows for echocardiography

Key Exclusion Criteria:

  • Any significant structural cardiac abnormalities on Screening TTE
  • At Screening, symptomatic hypotension or hypertension or bradycardia.
  • Routinely scheduled outpatient intravenous (IV) infusions for heart failure (e.g., inotropes, vasodilators [e.g., nesiritide], diuretics) or routinely scheduled ultrafiltration.
  • Presence of protocol specified laboratory abnormalities at Screening.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
52 participants (actual)

Study arms

  • Other
    Part 1/SAD and Part 2/MAD - drug

    Part 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo

    Drug: MYK-491

  • Other
    Part 1/SAD and Part 2/MAD - placebo

    Part 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo

    Drug: Placebo

Interventions

  • DrugMYK-491

    Single Ascending Dose and Multiple Ascending Dose of MYK-491

  • DrugPlacebo

    Single Ascending Dose and Multiple Ascending Dose of placebo

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Number of participants with any grade of treatment-emergent adverse events (TEAEs) and any grade of serious adverse events (SAEs).

    Time frame: From first dose to 30 days post last dose (Up to 2 months)

  2. Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts

    Number of participants with change from baseline in ECGs QTcF, PR, and QRS intervals. Baseline is defined as the last non-missing value prior to the corresponding period.

    Time frame: Baseline, day 1-16, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose

  3. Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts

    Number of participants with change from baseline in ECGs QTcF, PR, and QRS intervals. Baseline is defined as the last non-missing value prior to first randomized dose.

    Time frame: Baseline, Day 1-16, 2 hours pre-dose and at 7-, 24-, and 48-hours post final dose

  4. Mean Change From Baseline in Vital Signs Part 1 - SAD Cohorts

    Mean change from baseline in supine systolic blood pressure (SBP) and supine diastolic blood pressure (DBP) vital signs. Baseline is defined as the last non-missing value prior to the corresponding period.

    Time frame: Baseline and at 6-hours post-dose

  5. Mean Change From Baseline in Vital Signs Part 1 - MAD Cohorts

    Mean change from baseline in supine systolic blood pressure (SBP) and supine diastolic blood pressure (DBP) vital signs. Baseline is defined as the last non-missing value prior to first randomized dose

    Time frame: Baseline and at 6-hours post-dose

  6. Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts

    Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to the corresponding period.

    Time frame: Baseline and at 6-hours post-dose

  7. Mean Change From Baseline in Vital Signs Part 2 - MAD Cohorts

    Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to first randomized dose

    Time frame: Baseline and at 6-hours post-dose

  8. Number of Participants With a Troponin I Increase - SAD Cohorts

    Number of participants with a troponin increase is defined as when one of the following conditions was met (1) if the participant's troponin I value was normal prior to dosing (≤0.03 ng/mL), an elevated level on at least one measurement after start of dosing \>2×ULN for the specific assay (\>0.06 ng/mL) through Day 16. (2) If the participant's troponin I value was above the ULN for the specific assay prior to dosing, an increase \>0.03 ng/mL compared to baseline on at least one measurement after start of dosing through Day 16.

    Time frame: Baseline, day 1-3, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose

  9. Number of Participants With a Troponin I Increase - MAD Cohorts

    Number of participants with a troponin increase is defined as when one of the following conditions was met (1) if the participant's troponin I value was normal prior to dosing (≤0.03 ng/mL), an elevated level on at least one measurement after start of dosing \>2×ULN for the specific assay (\>0.06 ng/mL) through Day 16. (2) If the participant's troponin I value was above the ULN for the specific assay prior to dosing, an increase \>0.03 ng/mL compared to baseline on at least one measurement after start of dosing through Day 16.

    Time frame: Baseline, pre-dose and 7hr post dose on treatment day 1, day 2, day 5 and pre-dose and at 7-, 24-, and 48-hours post final dose

  10. Number of Participants With Clinically Significant Laboratory Abnormalities

    Number of participants with clinically significant laboratory abnormalities.

    Time frame: From first dose to 30 days post last dose (Up to 2 months)

  11. Number of Participants With Clinically Significant Physical Examinations Abnormalities

    Number of participants with clinically significant physical examinations abnormalities.

    Time frame: From first dose to 30 days post last dose (Up to 2 months)

Secondary outcomes

  1. Danicamtiv Maximum Observed Plasma Concentration (Cmax)

    Maximum observed plasma concentration (Cmax) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  2. Danicamtiv Time of Maximum Observed Plasma Concentration (Tmax)

    Time of maximum observed plasma concentration (Tmax) for Danicamtiv.

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  3. Area Under the Plasma Concentration-Time Curve (AUC)

    Area under the plasma concentration-time curve (AUC) for Danicamtiv including the following time points: (AUC(0-12))=from time 0 to 12 hours; (AUC(0-24))=from time 0 to 24 hours; (AUC(0-48))=from time 0 to 48 hours; (AUClast)=from time 0 up to the last measurable concentration; (AUC(0-∞))=from time 0 to infinity. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  4. Apparent First-order Terminal Elimination Half-life (t1/2)

    Apparent first-order terminal elimination half-life (t1/2).

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  5. Danicamtiv Accumulation Ratio for Maximum Observed Plasma Concentration AR(Cmax) - MAD Cohorts

    Accumulation ratio for maximum observed plasma concentration AR(Cmax) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  6. Accumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours AR(AUC(0-12)) - MAD Cohorts

    Accumulation ratio for area under the plasma concentration-time curve from time 0 to 12 hours AR(AUC(0-12)) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

    Time frame: 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose

  7. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - SAD Cohorts

    Mean change from baseline in TTE parameter systolic ejection time (SET) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose and at 3, 6, 9, and 24 hours post dose

  8. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - SAD Cohorts

    Mean change from baseline in TTE parameter left ventricular stroke volume (LVSV) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose and at 3, 6, 9, and 24 hours post dose

  9. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - SAD Cohorts

    Mean change from baseline in TTE parameter left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose and at 3, 6, 9, and 24 hours post dose

  10. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - MAD Cohorts

    Mean change from baseline in TTE parameter systolic ejection time (SET) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11

  11. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - MAD Cohorts

    Mean change from baseline in TTE parameter left ventricular stroke volume (LVSV) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11

  12. Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - MAD Cohorts

    Mean change from baseline in TTE parameter left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

    Time frame: Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11

07

Results

Posted Feb 2, 2023

Participant flow

Participant flow — Overall Study
MilestoneSAD Cohort 1SAD Cohort 2MAD Cohort 1MAD Cohort 2MAD Cohort 3MAD Cohort 4MAD Placebo
Started84699610
Completed blinded treatment period a8400000
Completed blinded treatment period b8400000
Completed blinded treatment period c8400000
Completed optional open-label treatment period d6000000
Completed8469969
Not completed0000001
Withdrew: Withdrawal by subject0000001

Outcome measures

PrimaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of participants with any grade of treatment-emergent adverse events (TEAEs) and any grade of serious adverse events (SAEs).

Time frame:
From first dose to 30 days post last dose (Up to 2 months)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
ParticipantsSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 PlaceboMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mgMAD Cohort Placebo
TEAEs2530013007644
SAEs0000000000100
PrimaryNumber of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts

Number of participants with change from baseline in ECGs QTcF, PR, and QRS intervals. Baseline is defined as the last non-missing value prior to the corresponding period.

Time frame:
Baseline, day 1-16, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose
Reported as:
Count of participants · Participants
Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts
ParticipantsSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 Placebo
Change in QTcF from Baseline > 30msec110000112
Change in QTcF from Baseline > 60msec000000001
Change in PR from baseline > 25%100000000
Change in QRS from baseline > 25%110000000
PrimaryNumber of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts

Number of participants with change from baseline in ECGs QTcF, PR, and QRS intervals. Baseline is defined as the last non-missing value prior to first randomized dose.

Time frame:
Baseline, Day 1-16, 2 hours pre-dose and at 7-, 24-, and 48-hours post final dose
Reported as:
Count of participants · Participants
Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts
ParticipantsMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mgMAD Cohort Placebo
Change in QTcF from Baseline > 30msec2513
Change in QTcF from Baseline > 60msec0011
Change in PR from baseline > 25%0001
Change in QRS from baseline > 25%1202
PrimaryMean Change From Baseline in Vital Signs Part 1 - SAD Cohorts

Mean change from baseline in supine systolic blood pressure (SBP) and supine diastolic blood pressure (DBP) vital signs. Baseline is defined as the last non-missing value prior to the corresponding period.

Time frame:
Baseline and at 6-hours post-dose
Reported as:
Mean · mmHg
Mean Change From Baseline in Vital Signs Part 1 - SAD Cohorts
mmHgSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 Placebo
Supine SBP-10.13 ± 12.23-11.38 ± 9.90-1.38 ± 15.0216.00 ± NA-7.00 ± 19.80-9.50 ± 2.122.50 ± 4.35901.75 ± 15.6500.00 ± 11.633
Supine DBP-5.50 ± 12.149.50 ± 6.44-5.75 ± 13.0412.00 ± NA-1.00 ± 5.66-4.00 ± 8.494.00 ± 9.933-2.25 ± 17.270-3.00 ± 14.674
PrimaryMean Change From Baseline in Vital Signs Part 1 - MAD Cohorts

Mean change from baseline in supine systolic blood pressure (SBP) and supine diastolic blood pressure (DBP) vital signs. Baseline is defined as the last non-missing value prior to first randomized dose

Time frame:
Baseline and at 6-hours post-dose
Reported as:
Mean · mmHg
Mean Change From Baseline in Vital Signs Part 1 - MAD Cohorts
mmHgMAD Cohorts DanicamtivMAD Cohorts Placebo
Supine SBP-4.86 ± 7.537-6.33 ± 3.215
Supine DBP-3.57 ± 7.323-5.67 ± 3.055
PrimaryMean Change From Baseline in Vital Signs Part 2 - SAD Cohorts

Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to the corresponding period.

Time frame:
Baseline and at 6-hours post-dose
Reported as:
Mean · Beats/min
Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts
Beats/minSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 Placebo
Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts7.13 ± 6.20-1.25 ± 5.753.00 ± 5.505.00 ± NA5.50 ± 0.71-1.50 ± 2.123.75 ± 9.743-0.50 ± 5.000-6.50 ± 13.699
PrimaryMean Change From Baseline in Vital Signs Part 2 - MAD Cohorts

Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to first randomized dose

Time frame:
Baseline and at 6-hours post-dose
Reported as:
Mean · Beats/min
Mean Change From Baseline in Vital Signs Part 2 - MAD Cohorts
Beats/minMAD Cohorts DanicamtivMAD Cohorts Placebo
Mean Change From Baseline in Vital Signs Part 2 - MAD Cohorts3.71 ± 2.5633.33 ± 2.517
PrimaryNumber of Participants With a Troponin I Increase - SAD Cohorts

Number of participants with a troponin increase is defined as when one of the following conditions was met (1) if the participant's troponin I value was normal prior to dosing (≤0.03 ng/mL), an elevated level on at least one measurement after start of dosing \>2×ULN for the specific assay (\>0.06 ng/mL) through Day 16. (2) If the participant's troponin I value was above the ULN for the specific assay prior to dosing, an increase \>0.03 ng/mL compared to baseline on at least one measurement after start of dosing through Day 16.

Time frame:
Baseline, day 1-3, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose
Reported as:
Count of participants · Participants
Number of Participants With a Troponin I Increase - SAD Cohorts
ParticipantsSAD Cohorts DanicamtivSAD Cohorts Placebo
Number of Participants With a Troponin I Increase - SAD Cohorts30
PrimaryNumber of Participants With a Troponin I Increase - MAD Cohorts

Number of participants with a troponin increase is defined as when one of the following conditions was met (1) if the participant's troponin I value was normal prior to dosing (≤0.03 ng/mL), an elevated level on at least one measurement after start of dosing \>2×ULN for the specific assay (\>0.06 ng/mL) through Day 16. (2) If the participant's troponin I value was above the ULN for the specific assay prior to dosing, an increase \>0.03 ng/mL compared to baseline on at least one measurement after start of dosing through Day 16.

Time frame:
Baseline, pre-dose and 7hr post dose on treatment day 1, day 2, day 5 and pre-dose and at 7-, 24-, and 48-hours post final dose
Reported as:
Count of participants · Participants
Number of Participants With a Troponin I Increase - MAD Cohorts
ParticipantsMAD Cohorts DanicamtivMAD Cohorts Placebo
Number of Participants With a Troponin I Increase - MAD Cohorts70
PrimaryNumber of Participants With Clinically Significant Laboratory Abnormalities

Number of participants with clinically significant laboratory abnormalities.

Time frame:
From first dose to 30 days post last dose (Up to 2 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Laboratory Abnormalities
ParticipantsSAD CohortsMAD Cohorts
Number of Participants With Clinically Significant Laboratory Abnormalities11
PrimaryNumber of Participants With Clinically Significant Physical Examinations Abnormalities

Number of participants with clinically significant physical examinations abnormalities.

Time frame:
From first dose to 30 days post last dose (Up to 2 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Physical Examinations Abnormalities
ParticipantsSAD CohortsMAD Cohorts
Number of Participants With Clinically Significant Physical Examinations Abnormalities00
SecondaryDanicamtiv Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration (Cmax) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Geometric mean · ng/mL
Danicamtiv Maximum Observed Plasma Concentration (Cmax)
ng/mLSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 350mg Period DSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
Danicamtiv Maximum Observed Plasma Concentration (Cmax)1476.63 ± NA2655.83 ± NA4420.00 ± NA3590.00 ± NA2718.51 ± NA5263.71 ± NA5337.58 ± NA5740.50 ± NA792.5 ± NA1174.3 ± NA1452.8 ± NA
SecondaryDanicamtiv Time of Maximum Observed Plasma Concentration (Tmax)

Time of maximum observed plasma concentration (Tmax) for Danicamtiv.

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Median · hours
Danicamtiv Time of Maximum Observed Plasma Concentration (Tmax)
hoursSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 350mg Period DSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
Danicamtiv Time of Maximum Observed Plasma Concentration (Tmax)5.14 (2.0 to 6.3)6.18 (3.7 to 9.1)12.0 (12.0 to 12.0)4.1 (4.1 to 4.1)5.74 (5.4 to 6.1)8.93 (7.9 to 9.9)9.13 (6.0 to 12.2)9.08 (6.0 to 10.0)4.983 (3.00 to 9.00)4.000 (1.00 to 12.05)3.500 (2.03 to 9.00)
SecondaryArea Under the Plasma Concentration-Time Curve (AUC)

Area under the plasma concentration-time curve (AUC) for Danicamtiv including the following time points: (AUC(0-12))=from time 0 to 12 hours; (AUC(0-24))=from time 0 to 24 hours; (AUC(0-48))=from time 0 to 48 hours; (AUClast)=from time 0 up to the last measurable concentration; (AUC(0-∞))=from time 0 to infinity. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Geometric mean · hr x ng/mL
Area Under the Plasma Concentration-Time Curve (AUC)
hr x ng/mLSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 350mg Period DSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
(AUC(0-12))————————7169.245 ± NA10310.794 ± NA12728.956 ± NA
(AUC(0-24))26411.97 ± NA48981.93 ± NA79175.02 ± NA70138.66 ± NA54004.82 ± NA97640.90 ± NA86110.51 ± NA97656.38 ± NA———
(AUC(0-48))40068.47 ± NA76497.78 ± NA143543.52 ± NA89356.54 ± NA89341.77 ± NA159193.47 ± NA135385.91 ± NA161073.09 ± NA———
(AUC last)46750.66 ± NA89216.40 ± NA182804.71 ± NA104060.46 ± NA106987.30 ± NA188544.49 ± NA—————
(AUC(0-∞))52467.20 ± NA99576.37 ± NA234888.37 ± NA—126374.56 ± NA211928.81 ± NA187776.56 ± NA225087.02 ± NA———
SecondaryApparent First-order Terminal Elimination Half-life (t1/2)

Apparent first-order terminal elimination half-life (t1/2).

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Mean · hours
Apparent First-order Terminal Elimination Half-life (t1/2)
hoursSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 Danicamtiv 450mgSAD Cohort 1 Danicamtiv 350mg Period DSAD Cohort 1 Danicamtiv 525mgSAD Cohort 1 Danicamtiv 550mgSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
Apparent First-order Terminal Elimination Half-life (t1/2)21.96 ± 4.4020.95 ± 3.2330.62 ± NA—24.73 ± 10.7621.45 ± 0.3024.45 ± 11.36324.30 ± 13.98724.466 ± 5.891120.573 ± 6.103323.319 ± 3.5903
SecondaryDanicamtiv Accumulation Ratio for Maximum Observed Plasma Concentration AR(Cmax) - MAD Cohorts

Accumulation ratio for maximum observed plasma concentration AR(Cmax) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Geometric mean · ng/mL
Danicamtiv Accumulation Ratio for Maximum Observed Plasma Concentration AR(Cmax) - MAD Cohorts
ng/mLMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
Danicamtiv Accumulation Ratio for Maximum Observed Plasma Concentration AR(Cmax) - MAD Cohorts3.451 ± NA3.241 ± NA3.827 ± NA
SecondaryAccumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours AR(AUC(0-12)) - MAD Cohorts

Accumulation ratio for area under the plasma concentration-time curve from time 0 to 12 hours AR(AUC(0-12)) for Danicamtiv. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported.

Time frame:
1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Reported as:
Geometric mean · hr x ng/mL
Accumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours AR(AUC(0-12)) - MAD Cohorts
hr x ng/mLMAD Cohort 2 Danicamtiv 50mgMAD Cohort 1+3 Danicamtiv 75mgMAD Cohort 4 Danicamtiv 100mg
Accumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours AR(AUC(0-12)) - MAD Cohorts3.983 ± NA3.696 ± NA4.607 ± NA
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - SAD Cohorts

Mean change from baseline in TTE parameter systolic ejection time (SET) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose and at 3, 6, 9, and 24 hours post dose
Reported as:
Mean · msec
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - SAD Cohorts
msecSAD Cohorts <2000 ng/mLSAD Cohorts ≥2000 ng/mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - SAD Cohorts8.04 ± 10.0336.3 ± 8.2
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - SAD Cohorts

Mean change from baseline in TTE parameter left ventricular stroke volume (LVSV) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose and at 3, 6, 9, and 24 hours post dose
Reported as:
Mean · mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - SAD Cohorts
mLSAD Cohorts <2000 ng/mLSAD Cohorts ≥2000 ng/mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - SAD Cohorts1.01 ± 3.679.01 ± 2.99
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - SAD Cohorts

Mean change from baseline in TTE parameter left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to the corresponding period. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose and at 3, 6, 9, and 24 hours post dose
Reported as:
Mean · Percentage of blood pumped from LV
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - SAD Cohorts
Percentage of blood pumped from LVSAD Cohorts <2000 ng/mLSAD Cohorts ≥2000 ng/mL
LVEF4.06 ± 2.274.44 ± 1.86
LVFS3.14 ± 1.362.81 ± 1.12
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - MAD Cohorts

Mean change from baseline in TTE parameter systolic ejection time (SET) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
Reported as:
Mean · msec
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - MAD Cohorts
msecMAD Cohorts <2000 ng/mLMAD Cohorts 2000-<3500 ng/mLMAD Cohorts ≥3500 ng/mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - MAD Cohorts15.1 ± 3.5135.6 ± 3.7848.3 ± 4.68
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - MAD Cohorts

Mean change from baseline in TTE parameter left ventricular stroke volume (LVSV) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
Reported as:
Mean · mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - MAD Cohorts
mLMAD Cohorts <2000 ng/mLMAD Cohorts 2000-<3500 ng/mLMAD Cohorts ≥3500 ng/mL
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - MAD Cohorts3.126 ± 1.83487.843 ± 1.95115.685 ± 2.4988
SecondaryMean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - MAD Cohorts

Mean change from baseline in TTE parameter left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) according to Danicamtiv plasma concentration ranges. Baseline is defined as the last non-missing value prior to first randomized dose. Reporting arms are not mutually exclusive

Time frame:
Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
Reported as:
Mean · Percentage of blood pumped from LV
Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - MAD Cohorts
Percentage of blood pumped from LVMAD Cohorts <2000 ng/mLMAD Cohorts 2000-<3500 ng/mLMAD Cohorts ≥3500 ng/mL
LVEF-0.25 ± 0.8721.12 ± 0.9282.29 ± 1.158
LVFS0.46 ± 0.5370.78 ± 0.5740.51 ± 0.725

Adverse events

Collected over Adverse Events and Serious Adverse Events were monitored from first dose to 30 days post last dose (Up to 2 months). Participants were assessed for All-cause mortality from their date of randomization to study completion (Up to approximately 20 months). Non-serious events are listed at a 3.3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
SAD Cohort 1 Danicamtiv 175mg0/8 (0%)0/8 (0%)3/8 (37.5%)
SAD Cohort 1 Danicamtiv 350mg0/8 (0%)0/8 (0%)5/8 (62.5%)
SAD Cohort 1 Placebo0/8 (0%)0/8 (0%)3/8 (37.5%)
SAD Cohort 1 Danicamtiv Optional Period D0/6 (0%)0/6 (0%)1/6 (16.7%)
SAD Cohort 2 Danicamtiv 400mg0/4 (0%)0/4 (0%)3/4 (75%)
SAD Cohort 2 Danicamtiv 500mg0/4 (0%)0/4 (0%)0/4 (0%)
SAD Cohort 2 Placebo0/4 (0%)0/4 (0%)0/4 (0%)
MAD Cohort 1 Danicamtiv 75mg0/6 (0%)1/6 (16.7%)2/6 (33.3%)
MAD Cohort 1 Placebo0/2 (0%)0/2 (0%)0/2 (0%)
MAD Cohort 2 Danicamtiv 50mg0/9 (0%)0/9 (0%)7/9 (77.8%)
MAD Cohort 2 Placebo0/3 (0%)0/3 (0%)1/3 (33.3%)
MAD Cohort 3 Danicamtiv 75mg0/9 (0%)0/9 (0%)6/9 (66.7%)
MAD Cohort 3 Placebo0/3 (0%)0/3 (0%)1/3 (33.3%)
MAD Cohort 4 Danicamtiv 100mg0/6 (0%)0/6 (0%)5/6 (83.3%)
MAD Cohort 4 Placebo0/2 (0%)0/2 (0%)2/2 (100%)
Most frequent serious events
Most frequent serious events
EventSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv Optional Period DSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 PlaceboMAD Cohort 1 Danicamtiv 75mgMAD Cohort 1 PlaceboMAD Cohort 2 Danicamtiv 50mgMAD Cohort 2 PlaceboMAD Cohort 3 Danicamtiv 75mgMAD Cohort 3 PlaceboMAD Cohort 4 Danicamtiv 100mgMAD Cohort 4 Placebo
HyperkalaemiaMetabolism and nutrition disorders0/80/80/80/60/40/40/41/60/20/90/30/90/30/60/2
Most frequent other events
Showing 10 of 59
Most frequent other events
EventSAD Cohort 1 Danicamtiv 175mgSAD Cohort 1 Danicamtiv 350mgSAD Cohort 1 PlaceboSAD Cohort 1 Danicamtiv Optional Period DSAD Cohort 2 Danicamtiv 400mgSAD Cohort 2 Danicamtiv 500mgSAD Cohort 2 PlaceboMAD Cohort 1 Danicamtiv 75mgMAD Cohort 1 PlaceboMAD Cohort 2 Danicamtiv 50mgMAD Cohort 2 PlaceboMAD Cohort 3 Danicamtiv 75mgMAD Cohort 3 PlaceboMAD Cohort 4 Danicamtiv 100mgMAD Cohort 4 Placebo
NasopharyngitisInfections and infestations0/80/80/80/60/40/40/40/60/20/90/30/90/30/61/2
HaematuriaRenal and urinary disorders0/80/80/80/60/40/40/40/60/20/90/30/90/30/61/2
Renal impairmentRenal and urinary disorders0/80/80/80/60/40/40/40/60/20/90/30/90/30/61/2
AnaemiaBlood and lymphatic system disorders0/80/80/80/61/40/40/40/60/20/90/31/91/30/60/2
Ventricular tachycardiaCardiac disorders0/80/80/80/60/40/40/40/60/22/90/30/90/32/60/2
Dry eyeEye disorders0/80/80/80/60/40/40/40/60/20/91/30/90/30/60/2
Vessel puncture site haemorrhageGeneral disorders0/80/80/80/60/40/40/42/60/20/90/30/90/30/60/2
Skin abrasionInjury, poisoning and procedural complications0/80/80/80/60/40/40/40/60/20/90/30/91/30/60/2
Traumatic haematomaInjury, poisoning and procedural complications0/80/80/80/60/40/40/40/60/20/90/30/91/30/60/2
ArthralgiaMusculoskeletal and connective tissue disorders0/80/80/80/60/40/40/40/60/20/91/30/90/30/60/2

Baseline characteristics

Age, Continuous
Age, Continuous(Years)SAD Cohort 1SAD Cohort 2MAD Cohort 1MAD Cohort 2MAD Cohort 3MAD Cohort 4MAD PlaceboTotal
Mean57.1 ± 9.457.5 ± 5.0762.7 ± 12.5063.0 ± 9.8656.8 ± 5.0958.5 ± 5.3658.6 ± 6.9859.2 ± 8.11
Sex: Female, Male
Sex: Female, Male(Participants)SAD Cohort 1SAD Cohort 2MAD Cohort 1MAD Cohort 2MAD Cohort 3MAD Cohort 4MAD PlaceboTotal
Female313321114
Male533675938
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)SAD Cohort 1SAD Cohort 2MAD Cohort 1MAD Cohort 2MAD Cohort 3MAD Cohort 4MAD PlaceboTotal
Hispanic or Latino00000011
Not Hispanic or Latino846996951
Unknown or Not Reported00000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)SAD Cohort 1SAD Cohort 2MAD Cohort 1MAD Cohort 2MAD Cohort 3MAD Cohort 4MAD PlaceboTotal
American Indian or Alaska Native00000000
Asian00000000
Native Hawaiian or Other Pacific Islander00000000
Black or African American613120316
White233876736
More than one race00000000
Unknown or Not Reported00000000
08

Study locations

17 sites
  • Jacksonville Center for Clinical Research
    Jacksonville, Florida 32216, United States
  • Prism Reseach
    Saint Paul, Minnesota 55102, United States
  • St. Louis Heart and Vascular Cardiology
    St Louis, Missouri 63136, United States
  • Newark Beth Israel Medical Center
    Newark, New Jersey 07112, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Ohio State University Medical Center
    Columbus, Ohio 43210, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • University of Pennsylvania Heart and Vascular Center
    Philadelphia, Pennsylvania 19104, United States
  • Tennessee Center for Clinical Trials
    Tullahoma, Tennessee 37388, United States
  • Hopital Europeen Georges-Pompidou
    Paris, 75015, France
  • Charite Research Organization
    Berlin, 10117, Germany
  • Groningen UMC
    Groningen, 9713 GZ, Netherlands
  • D&A Research
    Sneek, 8601, Netherlands
  • Wojewodzki Szpital Specjalistyczny Im M Kopernika
    Lodz, 93-513, Poland
  • Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny z Pododdzialem Intensywnego Nadzoru Kardiologicznego i Pododdzialem Leczenia Zaburzen Rytmu Serca
    Wroclaw, 51-124, Poland
  • Karolinska University Hospital
    Stockholm, 17164, Sweden
  • Queen Elizabeth University Hospital
    Glasgow, Scotland G51 4TF, United Kingdom
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 19, 2019

Documents are hosted by the registry — open the source record to download them.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Feb 2018 to primary completion in Oct 2019, 20 months.

Results were first posted in Feb 2023, 3 years 3 months after primary completion. A results delay was requested in Oct 2020.

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

Registered
Feb 14, 2018
First posted
Feb 27, 2018
StartActual
Feb 6, 2018
Primary completionActual
Oct 24, 2019
CompletionActual
Oct 24, 2019
Results delay requested
Oct 22, 2020
Results first posted
Feb 2, 2023
Last update
Feb 2, 2023
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 Feb 2, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03447990
Lead sponsor
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Feb 27, 2018
Start date
Feb 6, 2018
Primary completion
Oct 24, 2019
Completion
Oct 24, 2019
Results posted
Feb 2, 2023
Last update
Feb 2, 2023

Oversight

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

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