Phase 2
Completed N=52
v4 Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-491
Source: ClinicalTrials.gov NCT03447990 ↗Enrolled (actual)
52
Serious AEs
1.2%
Results posted
Feb 2023
Primary outcomePrimary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 2; 5; 3; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
2; 5; 3; 0; 0; 1 | — |
| PRIMARY Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts |
2; 5; 1; 3; 0; 0 | — |
| PRIMARY Mean Change From Baseline in Vital Signs Part 1 - SAD Cohorts |
-10.13; -11.38; -1.38; 16.00; -7.00; -9.50 | — |
| PRIMARY Mean Change From Baseline in Vital Signs Part 1 - MAD Cohorts |
-4.86; -6.33; -3.57; -5.67 | — |
| PRIMARY Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts |
7.13; -1.25; 3.00; 5.00; 5.50; -1.50 | — |
| PRIMARY Mean Change From Baseline in Vital Signs Part 2 - MAD Cohorts |
3.71; 3.33 | — |
| PRIMARY Number of Participants With a Troponin I Increase - SAD Cohorts |
3; 0 | — |
| PRIMARY Number of Participants With a Troponin I Increase - MAD Cohorts |
7; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities |
1; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Physical Examinations Abnormalities |
0; 0 | — |
| SECONDARY Danicamtiv Maximum Observed Plasma Concentration (Cmax) |
1476.63; 2655.83; 4420.00; 3590.00; 2718.51; 5263.71 | — |
| SECONDARY Danicamtiv Time of Maximum Observed Plasma Concentration (Tmax) |
5.14; 6.18; 12.0; 4.1; 5.74; 8.93 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve (AUC) |
7169.245; 10310.794; 12728.956; 26411.97; 48981.93; 79175.02 | — |
| SECONDARY Apparent First-order Terminal Elimination Half-life (t1/2) |
21.96; 20.95; 30.62; 24.73; 21.45; 24.45 | — |
| SECONDARY Danicamtiv Accumulation Ratio for Maximum Observed Plasma Concentration AR(Cmax) - MAD Cohorts |
3.451; 3.241; 3.827 | — |
| SECONDARY Accumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours AR(AUC(0-12)) - MAD Cohorts |
3.983; 3.696; 4.607 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - SAD Cohorts |
8.04; 36.3 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - SAD Cohorts |
1.01; 9.01 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - SAD Cohorts |
4.06; 4.44; 3.14; 2.81 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 1 - MAD Cohorts |
15.1; 35.6; 48.3 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 2 - MAD Cohorts |
3.126; 7.843; 5.685 | — |
| SECONDARY Mean Change From Baseline in Transthoracic Echocardiogram (TTE) Parameter 3 - MAD Cohorts |
-0.25; 1.12; 2.29; 0.46; 0.78; 0.51 | — |
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.
Data sourced from ClinicalTrials.gov (NCT03447990). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.