Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-986120 in Healthy Subjects and the Effects of Co-Administration of Midazolam and BMS-986120

Healthy Adult Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02208882
• Other study ID #: CV004-006
• Status: Completed
• Phase: Phase 1
• First received: August 4, 2014
• Last updated: July 3, 2015
• Start date: August 2014
• Est. completion date: February 2015

Study information

• Verified date: July 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

1. Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations

2. Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/[Height(m)]2

3. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and men, ages 18 to 75, inclusive

Exclusion Criteria:

1. 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

2. 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

3. Hemoglobin or hematocrit or platelet count <lower limit of normal (LLN)

4. Bleeding time exceeding 8 minutes at pre-dose on Day -1

5. 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

6. Any significant acute or chronic medical illness

7. Current or recent (within 3 months of study drug administration) gastrointestinal disease

8. Any major surgery within 12 weeks of study drug administration

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Adult Volunteers

Intervention

Drug:
• BMS-986120

• Placebo

• Midazolam

Locations

Country	Name	City	State
United States	Ppd Development, Lp	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Up to 168 days	Yes
Primary	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		Up to 168 days	Yes
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form