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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Drug: Danicamtiv
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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].

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Danicamtiv + Midazolam<br> | Drug: Danicamtiv<br>* Specified dose on specified days<br>* Other names: MYK-491;Drug: Midazolam<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HFrEF, Danicamtiv, BMS-986434, MYK-491, Midazolam