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

Recruitment & Eligibility

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].

Study & Design

Arm && Interventions

Group	Intervention	Description
Danicamtiv + Midazolam	Danicamtiv	-
Danicamtiv + Midazolam	Midazolam	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Number of participants with vital sign abnormalities	Up to Day 12
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 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

Trial Locations

Locations (5)

Research Integrity LLC

🇺🇸

Owensboro, Kentucky, United States

Holy Cross Hospital

🇺🇸

Fort Lauderdale, Florida, United States

Sinai Hospital Of Baltimore

🇺🇸

Baltimore, Maryland, United States

Jacksonville Center For Clinical Research

🇺🇸

Jacksonville, Florida, United States

Nature Coast Clinical Research

🇺🇸

Inverness, Florida, United States

Recruitment & Eligibility