Clinical trial NCT05952089: A Study to Assess the Effect of Danicamtiv on the Drug Levels of Midazolam in Participants With Stable Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: HFrEF
Danicamtiv
BMS-986434
MYK-491
Midazolam
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2023-07-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 \[sMDRD\].

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to Day 12
measure: Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF])
timeFrame: Up to Day 12
measure: Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC[0-T])
timeFrame: Up to Day 12
Secondary outcomes:
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Up to Day 12
measure: Terminal elimination half-life (T-HALF)
timeFrame: Up to Day 12
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to Day 12
measure: Number of participants with vital sign abnormalities
timeFrame: Up to Day 12
measure: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: Up to Day 12
measure: Number of participants with physical examination abnormalities
timeFrame: Up to Day 12
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Up to Day 11
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center For Clinical Research
state: Florida
city: Owensboro
country: United States
facility: Research Integrity LLC
state: Kentucky
city: Baltimore
country: United States
facility: Sinai Hospital Of Baltimore
state: Maryland
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: