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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
52
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States
Prism Reseach
Saint Paul, Minnesota, United States
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)
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
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
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
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
Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts
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St. Louis Heart and Vascular Cardiology
St Louis, Missouri, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Duke University Medical Center
Durham, North Carolina, United States
Ohio State University Medical Center
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pennsylvania Heart and Vascular Center
Philadelphia, Pennsylvania, United States
Tennessee Center for Clinical Trials
Tullahoma, Tennessee, United States
Hopital Europeen Georges-Pompidou
Paris, France
...and 7 more locations
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
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
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
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
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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