Clinical Trials/NCT02208882

NCT02208882

Completed

Phase 1

Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of BMS-986120 in Healthy Subjects and the Effect of BMS-986120 on the Pharmacokinetics of Midazolam in Healthy Subjects

Bristol-Myers Squibb1 site in 1 country24 target enrollmentAugust 2014

ConditionsHealthy Adult Volunteers

InterventionsBMS-986120 Placebo Midazolam

DrugsBMS-986120 Placebo Midazolam

Overview

Phase: Phase 1
Intervention: BMS-986120
Conditions: Healthy Adult Volunteers
Sponsor: Bristol-Myers Squibb
Enrollment: 24
Locations: 1
Primary Endpoint: Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the safety, tolerability and effect on Midazolam pharmacokinetics of multiple oral doses of BMS-986120 in healthy subjects.

Registry

clinicaltrials.gov

Start Date

August 2014

End Date

February 2015

Last Updated

10 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
•Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/\[Height(m)\]2
•Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and men, ages 18 to 75, inclusive

Exclusion Criteria

•Concurrent, or use within 2-weeks of study drug administration, of marketed or investigational, non-steroidal anti-inflammatory compounds (NSAIDS), aspirin or other antiplatelet agents, oral or parenteral anticoagulants
•Subjects at screening or prior to first dose with the following abnormal laboratory values upon repeat testing are excluded:
•i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>upper limit of normal (ULN)
•ii) Total bilirubin \>ULN, thyroid-stimulating hormone (TSH) \>1.5 x ULN with T4 within normal limits (Subjects with mild unconjugated hyperbilirubinemia due to Gilbert's syndrome are excluded)
•iii) CK \>3 x ULN (unless exercise related and CK-MB within normal limits)
•iv) Activated partial thromboplastin (aPTT) or Prothrombin Time (PT)/International Normalized Ratio (INR) \>ULN
•v) Blood urea nitrogen (BUN) or creatinine (Cr) \>ULN
•Hemoglobin or hematocrit or platelet count \<lower limit of normal (LLN)
•Bleeding time exceeding 8 minutes at pre-dose on Day -1
•Subjects with micro- or macro-hematuria and/or fecal occult blood detected during screening, baseline or documented during other recent medical assessment, unless deemed not clinically significant by the Investigator and Medical Monitor

Arms & Interventions

Panel 1: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: BMS-986120

Panel 1: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: Placebo

Panel 2: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: BMS-986120

Panel 2: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: Placebo

Panel 3: BMS-986120 or Placebo + Midazolam

BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified

Intervention: BMS-986120

Panel 3: BMS-986120 or Placebo + Midazolam

BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified

Intervention: Placebo

Panel 3: BMS-986120 or Placebo + Midazolam

BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified

Intervention: Midazolam

Panel 4: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: BMS-986120

Panel 4: BMS-986120 or Placebo

BMS-986120 or Placebo multiple dose by mouth as specified

Intervention: Placebo

Outcomes

Primary Outcomes

Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters

Time Frame: Up to 168 days

Safety and tolerability measured by percent of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters

Time Frame: Up to 168 days

Secondary Outcomes

Area under the concentration-time curve from time zero to 24h [AUC(TAU)] of BMS-986120 and BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Apparent total body clearance (CLT/F) of BMS-986120, Midazolam, and 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
AUC accumulation index (AI_AUC) of BMS-986120 and BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Half-life (T-HALF) of BMS-986120 and BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Midazolam and 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Midazolam and 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Concentration at the end of the dosing Interval (Ctau) of BMS-986120 and BMT-141464(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] of 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Maximum observed plasma concentration (Cmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Time of maximum observed plasma concentration (Tmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986120(Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22))
Change from baseline in protease-activated receptor-4 - agonist peptide (PAR4-AP) induced platelet aggregation of BMS-986120(Part A (Days 1-3) & Part B/C (Days 1-19))