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Completed

NCT Number: NCT05952089

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

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).

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Holy Cross Hospital, Fort Lauderdale, Florida, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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].

Treatment and study plan

Danicamtiv

Drug

Specified dose on specified days

Other names: BMS-986434, MYK-491

midazolam

Drug

Specified dose on specified days

Primary outcomes

  1. Maximum observed plasma concentration (Cmax)

    Time frame: Up to Day 12

  2. Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF])

    Time frame: Up to Day 12

  3. Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC[0-T])

    Time frame: Up to Day 12

Secondary outcomes

  1. Time of maximum observed plasma concentration (Tmax)

    Time frame: Up to Day 12

  2. Terminal elimination half-life (T-HALF)

    Time frame: Up to Day 12

  3. Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Time frame: Up to Day 12

  4. Number of participants with vital sign abnormalities

    Time frame: Up to Day 12

  5. Number of participants with electrocardiogram (ECG) abnormalities

    Time frame: Up to Day 12

  6. Number of participants with physical examination abnormalities

    Time frame: Up to Day 12

  7. Number of participants with clinical laboratory abnormalities

    Time frame: Up to Day 11

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jul 19, 2023
Registry last updated
Apr 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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