A Study to Assess the Effect of Danicamtiv on the Drug Levels of Midazolam in Participants With Stable Heart Failure

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05952089

Collaborator

(none)

Enrollment

Arm

7.4

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is assess the effect of danicamtiv, as an inducer on the drug levels of midazolam in participants with heart failure with reduced ejection fraction (HFrEF).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Reduced Ejection Fraction	Drug: Danicamtiv Drug: Midazolam	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Single-sequence Study to Evaluate the Effect of Coadministration of Danicamtiv on the Pharmacokinetics of Midazolam in Patients With Stable Heart Failure With Reduced Ejection Fraction

Anticipated Study Start Date :

Jul 17, 2023

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Feb 28, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Danicamtiv + Midazolam	Drug: Danicamtiv Specified dose on specified days Other Names: BMS-986434 MYK-491 Drug: Midazolam Specified dose on specified days

Arm

Intervention/Treatment

Experimental: Danicamtiv + Midazolam

Drug: Danicamtiv

Specified dose on specified days

Other Names:

BMS-986434

MYK-491

Drug: Midazolam

Specified dose on specified days

Outcome Measures

Primary Outcome Measures

Maximum observed plasma concentration (Cmax) [Up to Day 12]
Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF]) [Up to Day 12]
Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC[0-T]) [Up to Day 12]

Secondary Outcome Measures

Time of maximum observed plasma concentration (Tmax) [Up to Day 12]
Terminal elimination half-life (T-HALF) [Up to Day 12]
Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Up to Day 12]
Number of participants with vital sign abnormalities [Up to Day 12]
Number of participants with electrocardiogram (ECG) abnormalities [Up to Day 12]
Number of participants with physical examination abnormalities [Up to Day 12]
Number of participants with clinical laboratory abnormalities [Up to Day 11]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ambulatory participants with stable HFrEF due to any etiology.
Body mass index (BMI) of 18.0 kilogram per square meter (kg/m2) to 35.0 kg/m2 inclusive.
Documented left ventricular ejection fraction (LVEF) 15% to 45% (on 2 occasions), including at least once during Screening and confirmed by the Echo Core Laboratory (the absolute difference between the 2 LVEF values qualifying the participant should be < 12%).
Participant receiving chronic medication for the treatment of heart failure reflecting current guidelines, including at least one of the following, unless not tolerated or contraindicated:β-blocker, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or angiotensin receptor neprilysin inhibitor. Such treatments should have been given at stable doses for at least ≥ 2 weeks prior to screening with no plan to modify treatments during the study.
Sinus rhythm or stable atrial or ventricular pacing or persistent atrial fibrillation that is adequately rate-controlled to allow pharmacodynamic (PD) assessments by Transthoracic echocardiogram (TTE). NOTE: Participants with implanted cardioverter defibrillator (ICD), pacing, or cardiac resynchronization therapy are eligible provided device programming is unchanged starting 2 months prior to and throughout the dosing period.
Adequate acoustic windows, determined by the Echo Core Laboratory, to enable accurate TTE assessments.

Exclusion Criteria:

Presence of disqualifying cardiac rhythms that would preclude echocardiographic assessments, as determined by the Investigator, including: (a) rapid, inadequately rate controlled atrial fibrillation or (b) frequent premature ventricular contractions that might interfere with reliable echocardiographic measurements of left ventricular function.
History of bronchospasm, or history of respiratory depression or arrest, airway obstruction, oxygen desaturation, or apnea.
History of allergy to midazolam, other benzodiazepines, danicamtiv, related compounds, or excipients in the formulations.
Severe renal insufficiency (defined as current estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 by simplified Modification of Diet in Renal Disease equation [sMDRD].