An Ascending Dose Study of BMS-986259 to Study Safety in Healthy Participants

Study Overview
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Brief Summary
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A Randomized double blind, placebo controlled study of BMS-986259 to evaluate the safety and effectiveness of the drug amongst different conditions and populations.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BMS-986259 in Healthy Participants.

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: BMS-986259
* Other: Placebo
* Diagnostic Test: P-Aminohippurate
* Diagnostic Test: Iohexol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants with a body mass Index (BMI) of 18.0 kg/m^2 - 30.0 kg/m^2. Males and females not of child bearing potential. Participants in the Japanese Cohorts in Part C must be first-generation Japanese (born in Japan, not living outside of Japan for more than 10 years, and both parents are ethnically Japanese.) Exclusion Criteria: Any previous dosing in another cohort in the current study or participation in an investigational drug within 2 months prior to (the first) drug administration in the current study. Any Significant Acute or Chronic medical Illness, major surgery in 12 months, or so smoking or used smoking cessation in 3 months. Inability to be venipunctured and/or tolerate venous access. ,abnormalities in hemoglobin or positive screen for hepatitis C, Hepatitis B, Human Immunodeficiency Virus (HIV), including hepatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A SAD - A1 Cohort<br>Single Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part A SAD - A2 Cohort<br>Single Ascending dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part A SAD- A3 Cohort<br>Single Ascending dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part A SAD- A4 Cohort<br>Single Ascending dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part A SAD - A5 Cohort<br>Single Ascending dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part A SAD- A6 Cohort<br>Single Ascending dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part B MAD- B1 Cohort<br>Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part B MAD - B2 Cohort<br>Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part B MAD - B3 Cohort<br>Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part B MAD - B4 Cohort<br>Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part C JMAD - C1 Cohort<br>Japanese Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part C JMAD - C2 Cohort<br>Japanese Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|
| Experimental: Part C JMAD - C3 Cohort<br>Japanese Multiple Ascending Dose | Drug: BMS-986259<br>* Single and Multiple ascending dose from Dose 1 to Dose 5<br>Other: Placebo<br>* Placebo matching BMS-986259<br>Diagnostic Test: P-Aminohippurate<br>* Diagnostic Agent<br>Diagnostic Test: Iohexol<br>* Diagnostic Agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | Up to 7 weeks | 
| Incidence of Serious Adverse Events (SAEs) |  | up to 7 weeks | 
| AEs leading to discontinuation |  | Up to 7 weeks | 
| Number of clinically significant changes in vital signs |  | Up to 7 weeks | 
| Number of clinically significant changes in ECG (electrocardiogram) |  | Up to 7 weeks | 
| Number of clinically significant changes in physical examinations |  | Up to 7 weeks | 
| Number of clinically significant changes in clinical laboratory tests |  | Up to 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration(Cmax)- Part A SAD |  | up to 7 weeks | 
| Time of maximum observed concentration(Tmax)- Part A SAD |  | Up to 7 weeks | 
| Terminal elimination rate constant (Lz)-Part A SAD |  | up to 7 weeks | 
| Half life (T-HALF)- Part A SAD |  | Up to 7 weeks | 
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration(AUC(0-T)- Part A SAD |  | Up to 7 weeks | 
| Area under the concentration-time curve from time zero extrapolated to infinite time(AUC(INF)-Part A SAD |  | Up to 7 weeks | 
| Apparent total body clearance(CL/F)-Part A SAD |  | Up to 7 weeks | 
| Apparent volume of distribution at terminal phase(Vz/F)- Part A SAD |  | Up to 7 weeks | 
| Maximum observed concentration(Cmax)-Part B and Part C MAD | For day 1 , day 13 and day 14 | Up to 7 years | 
| Time of maximum observed concentration(Tmax)-Part B and Part C MAD | For day 1, day 13 and day 14 | Up tp 7 weeks | 
| Area under the concentration-time curve in one dosing interval(AUC(TAU)- Part B and Part C MAD | For day 1 and day 14 | Up to 7 weeks | 
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration(AUC(0-T)-Part B and Part C MAD | For Day 14 | Up to 7 weeks | 
| Terminal elimination rate constant (Lz)-Part B and Part C MAD | For day 14 | up to 7 weeks | 
| Half life (T-HALF)- Part B and Part C MAD | For day 14 | Up to 7 weeks | 
| Apparent total body clearance(CL/F)-Part B and Part C MAD | For day 14 | Up to 7 weeks | 
| Apparent volume of distribution at terminal phase(Vz/F)- Part B and Part C MAD | For day 14 | Up to 7 weeks | 
| Accumulation Ratio Cmax (AR(Cmax)-Part B and Part C MAD | For day 14 | Up to 7 weeks | 
| Accumulation Ratio AUC(TAU) (AR(AUC[TAU])- Part B and Part C MAD | for day 14 | Up to 7 weeks |