Clinical trial NCT06846866: A Study to Investigate the Safety, Tolerability, and Drug Levels of BMS-986419 (Part 1) and the Effects Multiple Doses of BMS-986419 on Cardiac Repolarization (Part 2) in Healthy Participants
Official title: A Phase 1, Double-blind, Placebo-controlled, Randomized Study of the Safety, Tolerability, and Pharmacokinetics of BMS-986419 (Part 1) and a Phase 1 Randomized, Double-blind, Positive-controlled, Placebo-controlled, Parallel, Nested-crossover (Moxifloxacin-placebo) Thorough QT/QTc Study to Evaluate the Effect of Multiple Doses of BMS-986419 on Cardiac Repolarization (Part 2) in Healthy Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: BMS-986419, healthy, QTC, pharmacokinetics, moxifloxacin
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety, tolerability, and pharmacokinetics of BMS-986419 (Part 1) and the effects of multiple doses of BMS-986419 on cardiac repolarization (Part 2) in healthy participants.


Eligibility criteria: Inclusion Criteria

* Participants must be healthy as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory assessments.
* Participants must have a Body mass index (BMI) between 18.0 and 30.0 kilograms/meter square (kg/m\^2), inclusive, at screening.

Exclusion Criteria

* Participants must not have any significant acute or chronic medical illness as determined by the investigator.
* Participants must not have any current or recent (within 3 months of study intervention administration) GI disease, liver and kidney that could possibly affect drug absorption, distribution, metabolism, and excretion, (e.g., bariatric procedure, Cholecystectomy, and any other GI surgery that could impact upon the absorption of study intervention).
* Participants must not have Gilbert Syndrome.
* Participants must not have a history of clinically relevant cardiac disease as determined by the investigator, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for ventricular arrhythmias (e.g., long QT syndrome, catecholamine polymorphic ventricular tachycardia).
* Participants must not have exposure to any investigational drug or placebo (other than BMS-986419 or moxifloxacin) within 4 weeks or 5 half-lives (whichever is longer) prior to Day -1 (Day -2 for Part 2) until follow-up phone call.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Part 1: Number of Participants with Non-serious Adverse Events (NSAEs)
timeFrame: Up to approximately Day 42
measure: Part 1: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to approximately Day 42
measure: Part 1: Number of Participants with AEs Leading to Discontinuation
timeFrame: Up to approximately Day 42
measure: Part 1: Number of Participants With AEs of Special Interest (AESI)
timeFrame: Up to approximately Day 42
measure: Part 1: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 1: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 1: Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 1: Number of Participants With Clinically Significant Columbia-Suicide Severity Rating Scale (C-SSRS) Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 1: Number of Participants With Clinically Significant Neurological Examination Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 1: Number of Participants With Physical Examination Abnormalities
timeFrame: Up to approximately Day 21
measure: Part 2: ΔQTc: Change From Baseline in Plasma Concentration of BMS-986419 on Cardiac Repolarization Expressed by QT interval (QTc)
timeFrame: Up to approximately Day 15
measure: Part 2: ΔΔQTc: Placebo-corrected Change From Baseline QTc Plasma Concentration of BMS-986419 on Cardiac Repolarization Expressed by QTc
timeFrame: Up to approximately Day 15
Secondary outcomes:
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Time of Maximum Plasma Observed Concentration (Tmax) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC [0-T]) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Terminal Phase Elimination Half-life (T-Half) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)] of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Apparent Total Body Clearance (CLT/F) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Apparent Volume of Distribution of Terminal Phase (Vz/F) of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 1: Trough Concentration of BMS-986419
timeFrame: Up to approximately Day 21
measure: Part 2: ΔQTc of BMS-986419 Using Change From Baseline of Heart Rate (HR)(ΔHR) Correction
timeFrame: Up to approximately Day 15
measure: Part 2: ΔQTc of BMS-986419 Using Change From Baseline of Pulse Rate (PR)(ΔPR) Correction
timeFrame: Up to approximately Day 15
measure: Part 2: ΔQTc of BMS-986419 Using Change From Baseline of Respiratory Rate (RR) Interval Correction
timeFrame: Up to approximately Day 15
measure: Part 2: Change From Baseline of BMS-986419 in Quality Rating System (QRS) Interval (ΔQRS)
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Treatment-emergent Values of Fridericia's Corrected QT interval (QTcF) for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Timepoints With Change in Absolute Treatment-emergent QTcF Values for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Treatment-emergent Values of Individualized Heart Rate-corrected Interval/Optimized HR-corrected QT Interval (QTcS/QTcI) for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Treatment-emergent Values of HR for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Timepoints With Change in Absolute Treatment-emergent HR Values for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Treatment-emergent Values of PR for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Timepoints With Increase in Absolute Treatment-emergent PR Values for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Treatment-emergent Values of QRS for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Timepoints With Increase in Absolute Treatment-emergent QRS Values for BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With New Onset ECG Morphology Findings
timeFrame: Up to approximately Day 15
measure: Part 2: ΔQTc: Change From Baseline in Plasma Concentration of Moxifloxacin on Cardiac Repolarization Expressed by QT interval (QTc)
timeFrame: Up to approximately Day 15
measure: Part 2: ΔΔQTc: Placebo-corrected Change From Baseline QTc Plasma Concentration of Moxifloxacin on Cardiac Repolarization Expressed by QTc
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants with NSAEs
timeFrame: Up to approximately Day 36
measure: Part 2: Number of Participants with SAEs
timeFrame: Up to approximately Day 36
measure: Part 2: Number of Participants with AEs Leading to Discontinuation
timeFrame: Up to approximately Day 36
measure: Part 2: Number of Participants With AESI
timeFrame: Up to approximately Day 36
measure: Part 2: Number of Participants With Clinically Significant Vital Sign Abnormalities
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities
timeFrame: Up to approximately Day 14
measure: Part 2: Number of Participants With Clinically Significant 12-Lead ECG Abnormalities
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Clinically Significant C-SSRS Abnormalities
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Clinically Significant Neurological Examination Abnormalities
timeFrame: Up to approximately Day 15
measure: Part 2: Number of Participants With Physical Examination Abnormalities
timeFrame: Up to approximately Day 15
measure: Part 2: Cmax of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Tmax of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: AUC(0-T) of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: AUC(TAU) of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: T-Half of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: AI_Cmax of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: AI_AUC(TAU) of BMS-986419
timeFrame: Up to approximately Day 15
measure: Part 2: Trough Concentration of BMS-986419
timeFrame: Up to approximately Day 15
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: