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

NCT05952089 | Completed Phase 1 FDA Drug

• 1 other identifier: CV028-009
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

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).

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

HFrEF; Danicamtiv; BMS-986434; MYK-491; Midazolam

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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

Study Arms (1)

Danicamtiv + Midazolam

EXPERIMENTAL

Drug: Danicamtiv; Drug: Midazolam

Interventions

Danicamtiv DRUG

Specified dose on specified days

Also known as: BMS-986434, MYK-491

Danicamtiv + Midazolam

Midazolam DRUG

Specified dose on specified days

Danicamtiv + Midazolam

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[sMDRD\].

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452, United States

Location

Jacksonville Center For Clinical Research

Jacksonville, Florida, 32216, United States

Location

Research Integrity LLC

Owensboro, Kentucky, 42303, United States

Location

Sinai Hospital Of Baltimore

Baltimore, Maryland, 21215, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: July 19, 2023
• Study Start: August 17, 2023
• Primary Completion: March 15, 2024
• Study Completion: March 19, 2024
• Last Updated: April 4, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)