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

Primary Purpose

Heart Failure With Reduced Ejection Fraction

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Danicamtiv
Midazolam
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring HFrEF, Danicamtiv, BMS-986434, MYK-491, Midazolam

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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].

Sites / Locations

  • Holy Cross HospitalRecruiting
  • Jacksonville Center For Clinical ResearchRecruiting
  • Research Integrity LLC
  • Sinai Hospital Of Baltimore
  • M Health Fairview St. John's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Danicamtiv + Midazolam

Arm Description

Outcomes

Primary Outcome Measures

Maximum observed plasma concentration (Cmax)
Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF])
Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration (AUC[0-T])

Secondary Outcome Measures

Time of maximum observed plasma concentration (Tmax)
Terminal elimination half-life (T-HALF)
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants with vital sign abnormalities
Number of participants with electrocardiogram (ECG) abnormalities
Number of participants with physical examination abnormalities
Number of participants with clinical laboratory abnormalities

Full Information

First Posted
July 11, 2023
Last Updated
September 29, 2023
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT05952089
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 17, 2023 (Actual)
Primary Completion Date
February 28, 2024 (Anticipated)
Study Completion Date
February 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction
Keywords
HFrEF, Danicamtiv, BMS-986434, MYK-491, Midazolam

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Danicamtiv + Midazolam
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Danicamtiv
Other Intervention Name(s)
BMS-986434, MYK-491
Intervention Description
Specified dose on specified days
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Specified dose on specified days
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax)
Time Frame
Up to Day 12
Title
Area under the plasma concentration time curve from time zero extrapolated to infinite time (AUC[INF])
Time Frame
Up to Day 12
Title
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 Outcome Measure Information:
Title
Time of maximum observed plasma concentration (Tmax)
Time Frame
Up to Day 12
Title
Terminal elimination half-life (T-HALF)
Time Frame
Up to Day 12
Title
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame
Up to Day 12
Title
Number of participants with vital sign abnormalities
Time Frame
Up to Day 12
Title
Number of participants with electrocardiogram (ECG) abnormalities
Time Frame
Up to Day 12
Title
Number of participants with physical examination abnormalities
Time Frame
Up to Day 12
Title
Number of participants with clinical laboratory abnormalities
Time Frame
Up to Day 11

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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].
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BMS Study Connect Contact Center www.BMSStudyConnect.com
Phone
855-907-3286
Email
Clinical.Trials@bms.com
First Name & Middle Initial & Last Name or Official Title & Degree
First line of the email MUST contain the NCT# and Site #.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Holy Cross Hospital
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Larned, Site 0005
Phone
954-229-8552
Facility Name
Jacksonville Center For Clinical Research
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Koren, Site 0003
Phone
904-730-0101
Facility Name
Research Integrity LLC
City
Owensboro
State/Province
Kentucky
ZIP/Postal Code
42303
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kishor Vora, Site 0004
Phone
270-691-1827
Facility Name
Sinai Hospital Of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Gurbel, Site 0001
Phone
410-601-4796
Facility Name
M Health Fairview St. John's Hospital
City
Maplewood
State/Province
Minnesota
ZIP/Postal Code
55109
Country
United States
Individual Site Status
Withdrawn

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

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

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