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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03447990
Other study ID # MYK-491-003
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date February 6, 2018
Est. completion date October 24, 2019

Study information

Verified date January 2023
Source Bristol-Myers Squibb
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 52
Est. completion date October 24, 2019
Est. primary completion date October 24, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
MYK-491
Single Ascending Dose and Multiple Ascending Dose of MYK-491
Placebo
Single Ascending Dose and Multiple Ascending Dose of placebo

Locations

Country Name City State
France Hopital Europeen Georges-Pompidou Paris
Germany Charite Research Organization Berlin
Netherlands Groningen UMC Groningen
Netherlands D&A Research Sneek
Poland Wojewodzki Szpital Specjalistyczny Im M Kopernika Lódz
Poland Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny z Pododdzialem Intensywnego Nadzoru Kardiologicznego i Pododdzialem Leczenia Zaburzen Rytmu Serca Wroclaw
Sweden Karolinska University Hospital Stockholm
United Kingdom Queen Elizabeth University Hospital Glasgow Scotland
United States Ohio State University Medical Center Columbus Ohio
United States Duke University Medical Center Durham North Carolina
United States Jacksonville Center for Clinical Research Jacksonville Florida
United States Newark Beth Israel Medical Center Newark New Jersey
United States University of Pennsylvania Heart and Vascular Center Philadelphia Pennsylvania
United States Oregon Health & Science University Portland Oregon
United States St. Louis Heart and Vascular Cardiology Saint Louis Missouri
United States Prism Reseach Saint Paul Minnesota
United States Tennessee Center for Clinical Trials Tullahoma Tennessee

Sponsors (1)

Lead Sponsor Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Germany,  Netherlands,  Poland,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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). From first dose to 30 days post last dose (Up to 2 months)
Primary 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. Baseline, day 1-16, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose
Primary 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. Baseline, Day 1-16, 2 hours pre-dose and at 7-, 24-, and 48-hours post final dose
Primary 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. Baseline and at 6-hours post-dose
Primary 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 Baseline and at 6-hours post-dose
Primary 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. Baseline and at 6-hours post-dose
Primary 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 Baseline and at 6-hours post-dose
Primary 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. Baseline, day 1-3, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose
Primary 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. 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
Primary Number of Participants With Clinically Significant Laboratory Abnormalities Number of participants with clinically significant laboratory abnormalities. From first dose to 30 days post last dose (Up to 2 months)
Primary Number of Participants With Clinically Significant Physical Examinations Abnormalities Number of participants with clinically significant physical examinations abnormalities. From first dose to 30 days post last dose (Up to 2 months)
Secondary 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. 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary Danicamtiv Time of Maximum Observed Plasma Concentration (Tmax) Time of maximum observed plasma concentration (Tmax) for Danicamtiv. 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary 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(0-8))=from time 0 to infinity. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary Apparent First-order Terminal Elimination Half-life (t1/2) Apparent first-order terminal elimination half-life (t1/2). 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary 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. 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary 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. 1 hour pre-dose and day 1-12 at 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 hours postdose
Secondary 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 Baseline, predose and at 3, 6, 9, and 24 hours post dose
Secondary 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 Baseline, predose and at 3, 6, 9, and 24 hours post dose
Secondary 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 Baseline, predose and at 3, 6, 9, and 24 hours post dose
Secondary 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 Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
Secondary 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 Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
Secondary 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 Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11
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