A Study to Assess Relative Bioavailability of Branebrutinib, From a Tablet Formulation to the Capsule Formulation, the Effect of Food on the Bioavailability of Branebrutinib From a Tablet Formulation, and the Safety and Drug Levels of Branebrutinib From a Tablet Formulation in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess the relative bioavailability of branebrutinib tablet formulation relative to the capsule formulation in order to identify doses that would provide exposures similar to the capsule formulation over the dose range that may be used in future clinical studies, evaluate the effect of food on the bioavailability of branebrutinib from a tablet formulation at a dose projected to provide similar pharmacokinetics (PK) as the 9 mg capsule formulation, and evaluate the safety and the PK of multiple oral dose of tablet formulation of branebrutinib in healthy participants.

Official Title
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A Phase 1, Open-label, Randomized, Crossover Study to Evaluate the Bioavailability of Branebrutinib in a Tablet Formulation Relative to Branebrutinib (RBA) in a Capsule Formulation Including the Effect of Food (Low-fat/Low-calorie and a High-fat/High-calorie) on the Bioavailability of Branebrutinib From a Tablet Formulation and a Double-blind Study to Evaluate the Safety and Pharmacokinetics of Branebrutinib From a Tablet Formulation in a Multiple-dose Arm in Healthy Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Branebrutinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female participants, of any race, as determined by no deviation considered significant by the investigator from normal in medical history, physical examination, 12-lead ECG measurements, and clinical laboratory determinations at screening or at check-in Body mass index (BMI) 18.0 to 33.0 kg/m2, inclusive. BMI = weight (kg)/(height [m])2 for participants Participant is afebrile (febrile is defined as ≥ 38°C or ≥100.4°F), with systolic blood pressure ≥ 90 and ≤ 160 mm Hg, diastolic blood pressure ≥ 50 and ≤ 100 mm Hg, and pulse rate ≥ 40 and ≤ 100 beats per minute at screening Exclusion Criteria: Any significant acute or chronic medical illness that presents a potential risk to the participant in the opinion of the investigator and/or may compromise the objectives of the study History of clinically significant endocrine, gastrointestinal (GI), cardiovascular (CV), peripheral vascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary (GU) abnormalities/diseases History of acute or chronic bacterial, fungal, or viral infection necessitating treatment or inpatient admission within the 3 months prior to screening, or active/symptomatic infection at the time of screening Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Treatment A<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 1 Treatment B<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 1 Treatment C<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 1 Treatment D<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 2 Treatment A<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 2 Treatment B<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 2 Treatment C<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Experimental: Part 3 Treatment A<br> | Drug: Branebrutinib<br>* Specified dose on specified days<br>* Other names: BMS-986195;|
| Placebo Comparator: Part 3 Treatment B<br> | Drug: Placebo<br>* Specified Dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) |  | Up to Day 14 | 
| Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable concentration (AUC(0-T)) |  | Up to Day 14 | 
| AUC from time zero extrapolated to infinite time (AUC(INF)) |  | Up to Day 14 | 
| Number of participants with adverse events (AEs) |  | Up to 30 days post last scheduled visit | 
| Number of participants with vital sign abnormalities |  | Up to Day 14 | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | Up to Day 14 | 
| Number of participants with physical examination abnormalities |  | Up to Day 14 | 
| Number of participants with clinical laboratory abnormalities |  | Up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean ratio of Cmax |  | Up to Day 17 | 
| Geometric mean ratio of AUC(0-T) |  | Up to Day 17 | 
| Geometric mean ratio of AUC(INF) |  | Up to Day 17 | 
| Time of maximum observed plasma concentration (Tmax) |  | Up to Day 17 | 
| Apparent total body clearance (CLT/F) |  | Up to Day 14 | 
| Apparent volume of distribution (Vz/F) |  | Up to Day 14 | 
| Number of participants with AEs |  | Up to 30 days post last scheduled visit | 
| Number of participants with vital sign abnormalities |  | Up to Day 14 | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | Up to Day 14 | 
| Number of participants with physical examination abnormalities |  | Up to Day 14 | 
| Number of participants with clinical laboratory abnormalities |  | Up to Day 14 |