Heart Failure With Reduced Ejection FractionPhase 1/2NCT03447990

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

A Phase 1/2 study testing MYK-491 in people with Heart Failure With Reduced Ejection Fraction and Dilated Cardiomyopathy, run by Bristol-Myers Squibb at 17 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Heart Failure With Reduced Ejection Fraction, Dilated Cardiomyopathy
What is being tested?: MYK-491
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 52 participants
Where: 17 sitesin 7 countries
Study dates: 6 Feb 2018to 24 Oct 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

17 sites in 7 countries.

Country

City, postcode or hospital

17 sites in 7 countries

United States9 sites

Ohio State University Medical Center
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
University of Pennsylvania Heart and Vascular Center
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Prism Reseach
Saint Paul, Minnesota, 55102
St. Louis Heart and Vascular Cardiology
St Louis, Missouri, 63136
Tennessee Center for Clinical Trials
Tullahoma, Tennessee, 37388

Other trials in United States

Netherlands2 sites

Groningen UMC
Groningen, 9713 GZ
D&A Research
Sneek, 8601

Other trials in Netherlands

Poland2 sites

Wojewodzki Szpital Specjalistyczny Im M Kopernika
Lodz, 93-513
Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny z Pododdzialem Intensywnego Nadzoru Kardiologicznego i Pododdzialem Leczenia Zaburzen Rytmu Serca
Wroclaw, 51-124

Other trials in Poland

France1 site

Hopital Europeen Georges-Pompidou
Paris, 75015

Other trials in France

Germany1 site

Charite Research Organization
Berlin, 10117

Other trials in Germany

Sweden1 site

Karolinska University Hospital
Stockholm, 17164

Other trials in Sweden

United Kingdom1 site

Queen Elizabeth University Hospital
Glasgow, Scotland, G51 4TF

Other trials in United Kingdom

About this study

Official title: Randomized, Double-blind, Placebo-controlled, Two-Part, Adaptive Design Study of Safety, Tolerability, Preliminary Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of MYK-491 in Patients With Stable Heart Failure With Reduced Ejection Fraction

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.

Conditions: Heart Failure With Reduced Ejection Fraction, Dilated Cardiomyopathy
Being tested: MYK-491, Placebo
Medical subject headings: Cardiomyopathy, Dilated

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MYK-491Drug
Single Ascending Dose and Multiple Ascending Dose of MYK-491
PlaceboDrug
Single Ascending Dose and Multiple Ascending Dose of placebo

Study groups in NCT03447990
Study group	Role	What they receive
Part 1/SAD and Part 2/MAD - drug	Other	Part 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo Receives: Drug: MYK-491
Part 1/SAD and Part 2/MAD - placebo	Other	Part 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline and at 6-hours post-dose
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From first dose to 30 days post last dose (Up to 2 months)

Secondary outcomes (12)

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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Feb 201824 Oct 2019

First posted27 Feb 2018
Study start6 Feb 2018
Primary completion24 Oct 2019
Study completion24 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This is a a two part study. The first part is a randomized, crossover, double-blind, placebo-controlled, two cohort, sequential ascending single dose study. All patients will receive placebo and active doses of MYK-491. The second part is a randomized, parallel, double-blind, placebo-controlled, sequential ascending multiple dose study. All patients will receive placebo and/or active doses of MYK-491.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03447990
Sponsor's protocol ID: MYK-491-003
Status last verified: Jan 2023
First submitted: 14 Feb 2018
Last updated: 2 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Assessment of CCM in HF With Higher Ejection Fraction
Heart Failure, Heart Failure With Preserved Ejection Fraction
Recruiting
Synchronized Diaphragmatic Stimulation in Symptomatic Heart Failure
Heart Failure With Reduced Ejection Fraction
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07328948 in Adults With Heart Failure (BRANCH-HF)
Heart Failure
RecruitingPhase 3
Qishen Yiqi Dripping Pills in Treatment of Chronic Heart FailUre
Heart Failure
RecruitingPhase 1/2
Endocardial Delivery for Myocardial Regeneration Using Allogeneic iPSC-derived Cardiomyocyte Spheroids for HF With Systolic Dysfunction (EMERALD Study)
Heart Failure, Ischemic Heart Failure

All Heart Failure With Reduced Ejection Fraction trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Double-blind, Placebo-controlled, Two-Part, Adaptive Design Study of Safety, Tolerability, Preliminary Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of MYK-491 in Patients With Stable Heart Failure With Reduced Ejection Fraction
ClinicalTrials.gov ID: NCT03447990
Acronym / sponsor ID: MYK-491-003
Conditions: Heart Failure With Reduced Ejection Fraction, Dilated Cardiomyopathy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: 6 Feb 2018 (actual)
Primary completion: 24 Oct 2019 (actual)
Study completion: 24 Oct 2019 (actual)
First posted: 27 Feb 2018 (actual)
Results: Posted 2 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: This is a a two part study. The first part is a randomized, crossover, double-blind, placebo-controlled, two cohort, sequential ascending single dose study. All patients will receive placebo and active doses of MYK-491. The second part is a randomized, parallel, double-blind, placebo-controlled, sequential ascending multiple dose study. All patients will receive placebo and/or active doses of MYK-491.

Arm	Type	Receives
Part 1/SAD and Part 2/MAD - drug	Other	Drug: MYK-491Part 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo
Part 1/SAD and Part 2/MAD - placebo	Other	Drug: PlaceboPart 1/SAD: Crossover, Single ascending dose of MYK-491/placebo Part 2/MAD: Parallel, multiple ascending dose of MYK-491/placebo

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MYK-491Single Ascending Dose and Multiple Ascending Dose of MYK-491	Drug	Part 1/SAD and Part 2/MAD - drug
PlaceboSingle Ascending Dose and Multiple Ascending Dose of placebo	Drug	Part 1/SAD and Part 2/MAD - placebo

Primary outcome

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose to 30 days post last dose (Up to 2 months)
Number of participants with any grade of treatment-emergent adverse events (TEAEs) and any grade of serious adverse events (SAEs).
Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts
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 ECGs QTcF, PR, and QRS intervals. Baseline is defined as the last non-missing value prior to the corresponding period.
Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts
Time frame: Baseline, Day 1-16, 2 hours pre-dose and at 7-, 24-, and 48-hours post final dose
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.
Mean Change From Baseline in Vital Signs Part 1 - SAD Cohorts
Time frame: Baseline and at 6-hours post-dose
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.
Mean Change From Baseline in Vital Signs Part 1 - MAD Cohorts
Time frame: Baseline and at 6-hours post-dose
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
Mean Change From Baseline in Vital Signs Part 2 - SAD Cohorts
Time frame: Baseline and at 6-hours post-dose
Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to the corresponding period.
Mean Change From Baseline in Vital Signs Part 2 - MAD Cohorts
Time frame: Baseline and at 6-hours post-dose
Mean change from baseline in heart rate (HR) vital signs. Baseline is defined as the last non-missing value prior to first randomized dose
Number of Participants With a Troponin I Increase - SAD Cohorts
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 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.
Number of Participants With a Troponin I Increase - MAD Cohorts
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 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.
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 laboratory 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)
Number of participants with clinically significant physical examinations abnormalities.

12 secondary outcomes

Danicamtiv Maximum Observed Plasma Concentration (Cmax)
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 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)
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)
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
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
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
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
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
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
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
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
Time frame: Baseline, predose, and at 7 hours post dose on day 1,2,3, 4, 7, 9, 10, and 11

Results and safety

Results posted to the registry on 2 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SAD Cohort 1	8	8
SAD Cohort 2	4	4
MAD Cohort 1	6	6
MAD Cohort 2	9	9
MAD Cohort 3	9	9
MAD Cohort 4	6	6
MAD Placebo	10	9

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame: From first dose to 30 days post last dose (Up to 2 months). Count of participants. Unit: Participants

Measure	SAD Cohort 1 Danicamtiv 175mg n = 8	SAD Cohort 1 Danicamtiv 350mg n = 8	SAD Cohort 1 Placebo n = 8	SAD Cohort 1 Danicamtiv 450mg n = 1	SAD Cohort 1 Danicamtiv 525mg n = 2	SAD Cohort 1 Danicamtiv 550mg n = 2	SAD Cohort 2 Danicamtiv 400mg n = 4	SAD Cohort 2 Danicamtiv 500mg n = 4	SAD Cohort 2 Placebo n = 4	MAD Cohort 2 Danicamtiv 50mg n = 9	MAD Cohort 1+3 Danicamtiv 75mg n = 15	MAD Cohort 4 Danicamtiv 100mg n = 6	MAD Cohort Placebo n = 10
TEAEs	2	5	3	0	0	1	3	0	0	7	6	4	4
SAEs	0	0	0	0	0	0	0	0	0	0	1	0	0

Population analysed: All treated participants per regimen dosage

Primary outcome: Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - SAD Cohorts

Time frame: Baseline, day 1-16, 2 hours pre-dose and at 3-, 5-, 9-, 12-, 24-, and 36-hours post-dose. Count of participants. Unit: Participants

Measure	SAD Cohort 1 Danicamtiv 175mg n = 8	SAD Cohort 1 Danicamtiv 350mg n = 8	SAD Cohort 2 Danicamtiv 400mg n = 4	SAD Cohort 2 Danicamtiv 500mg n = 4	SAD Cohort 2 Placebo n = 4
Change in QTcF from Baseline > 30msec	1	1	1	1	2
Change in QTcF from Baseline > 60msec	0	0	0	0	1
Change in PR from baseline > 25%	1	0	0	0	0
Change in QRS from baseline > 25%	1	1	0	0	0

Population analysed: All treated participants in SAD Cohorts per regimen dosage

Primary outcome: Number of Participants With Change From Baseline in Electrocardiograms (ECG) Intervals - MAD Cohorts

Time frame: Baseline, Day 1-16, 2 hours pre-dose and at 7-, 24-, and 48-hours post final dose. Count of participants. Unit: Participants

Measure	MAD Cohort 2 Danicamtiv 50mg n = 9	MAD Cohort 1+3 Danicamtiv 75mg n = 15	MAD Cohort 4 Danicamtiv 100mg n = 6	MAD Cohort Placebo n = 10
Change in QTcF from Baseline > 30msec	2	5	1	3
Change in QTcF from Baseline > 60msec	0	0	1	1
Change in PR from baseline > 25%	0	0	0	1
Change in QRS from baseline > 25%	1	2	0	2

Population analysed: All treated participants in MAD Cohorts per regimen dosage

Primary outcome: Mean Change From Baseline in Vital Signs Part 1 - SAD Cohorts

Time frame: Baseline and at 6-hours post-dose. Mean (Standard Deviation). Unit: mmHg

Measure	SAD Cohort 1 Danicamtiv 175mg n = 8	SAD Cohort 1 Danicamtiv 350mg n = 8	SAD Cohort 1 Placebo n = 8	SAD Cohort 1 Danicamtiv 450mg n = 1	SAD Cohort 1 Danicamtiv 525mg n = 2	SAD Cohort 1 Danicamtiv 550mg n = 2	SAD Cohort 2 Danicamtiv 400mg n = 4	SAD Cohort 2 Danicamtiv 500mg n = 4	SAD Cohort 2 Placebo n = 4
Supine SBP	-10.13 (12.23)	-11.38 (9.90)	-1.38 (15.02)	16.00 (NA)	-7.00 (19.80)	-9.50 (2.12)	2.50 (4.359)	01.75 (15.650)	0.00 (11.633)
Supine DBP	-5.50 (12.14)	9.50 (6.44)	-5.75 (13.04)	12.00 (NA)	-1.00 (5.66)	-4.00 (8.49)	4.00 (9.933)	-2.25 (17.270)	-3.00 (14.674)

Population analysed: All treated participants in SAD Cohorts per regimen dosage

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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). Other adverse events reported at 3.3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SAD Cohort 1 Danicamtiv 175mg	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
SAD Cohort 1 Danicamtiv 350mg	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
SAD Cohort 1 Placebo	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
SAD Cohort 1 Danicamtiv Optional Period D	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
SAD Cohort 2 Danicamtiv 400mg	0 of 4 (0%)	3 of 4 (75%)	0 of 4
SAD Cohort 2 Danicamtiv 500mg	0 of 4 (0%)	0 of 4 (0%)	0 of 4
SAD Cohort 2 Placebo	0 of 4 (0%)	0 of 4 (0%)	0 of 4
MAD Cohort 1 Danicamtiv 75mg	1 of 6 (16.7%)	2 of 6 (33.3%)	0 of 6
MAD Cohort 1 Placebo	0 of 2 (0%)	0 of 2 (0%)	0 of 2
MAD Cohort 2 Danicamtiv 50mg	0 of 9 (0%)	7 of 9 (77.8%)	0 of 9
MAD Cohort 2 Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
MAD Cohort 3 Danicamtiv 75mg	0 of 9 (0%)	6 of 9 (66.7%)	0 of 9
MAD Cohort 3 Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
MAD Cohort 4 Danicamtiv 100mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
MAD Cohort 4 Placebo	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Heart Failure With Reduced Ejection Fraction

Recruiting
Assessment of CCM in HF With Higher Ejection Fraction
Heart Failure, Heart Failure With Preserved Ejection Fraction
Recruiting
Synchronized Diaphragmatic Stimulation in Symptomatic Heart Failure
Heart Failure With Reduced Ejection Fraction
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07328948 in Adults With Heart Failure (BRANCH-HF)
Heart Failure
RecruitingPhase 3
Qishen Yiqi Dripping Pills in Treatment of Chronic Heart FailUre
Heart Failure
RecruitingPhase 1/2
Endocardial Delivery for Myocardial Regeneration Using Allogeneic iPSC-derived Cardiomyocyte Spheroids for HF With Systolic Dysfunction (EMERALD Study)
Heart Failure, Ischemic Heart Failure

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

17 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MYK-491 in people with Heart Failure With Reduced Ejection Fraction and Dilated Cardiomyopathy, run by Bristol-Myers Squibb at 17 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Netherlands, Poland, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: From first dose to 30 days post last dose (Up to 2 months)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03447990.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2023.