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

Heart Failure With Reduced Ejection Fraction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05952089
• Other study ID #: CV028-009
• Status: Completed
• Phase: Phase 1
• Start date: August 17, 2023
• Est. completion date: March 19, 2024

Study information

• Verified date: April 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 19, 2024
• Est. primary completion date: March 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

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:ß-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].

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• Danicamtiv
Specified dose on specified days
• Midazolam
Specified dose on specified days

Locations

Country	Name	City	State
United States	Sinai Hospital Of Baltimore	Baltimore	Maryland
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Nature Coast Clinical Research	Inverness	Florida
United States	Jacksonville Center For Clinical Research	Jacksonville	Florida
United States	Research Integrity LLC	Owensboro	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax)		Up to Day 12
Primary	Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF])		Up to Day 12
Primary	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	Time of maximum observed plasma concentration (Tmax)		Up to Day 12
Secondary	Terminal elimination half-life (T-HALF)		Up to Day 12
Secondary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to Day 12
Secondary	Number of participants with vital sign abnormalities		Up to Day 12
Secondary	Number of participants with electrocardiogram (ECG) abnormalities		Up to Day 12
Secondary	Number of participants with physical examination abnormalities		Up to Day 12
Secondary	Number of participants with clinical laboratory abnormalities		Up to Day 11

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting