A Study to Assess the Effect of BMS-986142 on Pharmacokinetics (PK) of Probe Substrates
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-986142 200mg
BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)
BMS-986142 350mg
Sponsored by
About this trial
This is an interventional basic science trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Signed Informed Consent
- Target population: Healthy (current non-smokers) subjects as determined by medical history, surgical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory determinations.
- Subjects with body mass index of 18 to 32 kg/m2, inclusive
- Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and must not be breastfeeding.
- Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of the study drug (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days (approximately 14 weeks) after treatment completion. Female partners of male subjects are expected to use one of the highly effective methods of contraception listed in the protocol.
Exclusion Criteria:
- History of any chronic or acute illness, recent infection, gastrointestinal disease, smoking and alcohol abuse, any significant drug allergy or allergy to digoxin, flurbiprofen, midazolam, omeprazole, or montelukast, Bruton's tyrosine kinase (BTK) inhibitors, immunologic or related compounds.
- History of billiary disorder, asthma, bleeding disorder, cancer
- Received live vaccine during last 12 weeks, active tuberculosis (TB) in last 3 years
- Medical history indicative of an increased risk of arrhythmia.
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population.
Sites / Locations
- Ppd Development, Lp
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1 (BMS-986142: 200 mg)
Cohort 2 (BMS-986142: 350 mg)
Arm Description
200mg BMS-986142 administered orally once daily on specified days.
350mg BMS-986142 administered orally once daily on specified days.
Outcomes
Primary Outcome Measures
Maximum observed plasma concentration (Cmax) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin.
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin
Secondary Outcome Measures
Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02762123
Brief Title
A Study to Assess the Effect of BMS-986142 on Pharmacokinetics (PK) of Probe Substrates
Official Title
Effects of Concomitant Administration of BMS-986142 on the Single-dose Pharmacokinetics of Probe Substrates for CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-gp in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study is being conducted to assess the effect of BMS-986142 on the single-dose PK parameters of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin, probe drugs for (cytochome P450) CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein (P-gp), respectively.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 (BMS-986142: 200 mg)
Arm Type
Experimental
Arm Description
200mg BMS-986142 administered orally once daily on specified days.
Arm Title
Cohort 2 (BMS-986142: 350 mg)
Arm Type
Experimental
Arm Description
350mg BMS-986142 administered orally once daily on specified days.
Intervention Type
Drug
Intervention Name(s)
BMS-986142 200mg
Intervention Type
Drug
Intervention Name(s)
BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)
Intervention Type
Drug
Intervention Name(s)
BMS-986142 350mg
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin.
Time Frame
57 samples up to day 26
Title
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin
Time Frame
57 samples up to day 26
Title
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin
Time Frame
57 samples up to day 26
Secondary Outcome Measure Information:
Title
Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death
Time Frame
Days 1-26; for SAEs up to 30 days post discontinuation of dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Signed Informed Consent
Target population: Healthy (current non-smokers) subjects as determined by medical history, surgical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory determinations.
Subjects with body mass index of 18 to 32 kg/m2, inclusive
Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and must not be breastfeeding.
Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of the study drug (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days (approximately 14 weeks) after treatment completion. Female partners of male subjects are expected to use one of the highly effective methods of contraception listed in the protocol.
Exclusion Criteria:
History of any chronic or acute illness, recent infection, gastrointestinal disease, smoking and alcohol abuse, any significant drug allergy or allergy to digoxin, flurbiprofen, midazolam, omeprazole, or montelukast, Bruton's tyrosine kinase (BTK) inhibitors, immunologic or related compounds.
History of billiary disorder, asthma, bleeding disorder, cancer
Received live vaccine during last 12 weeks, active tuberculosis (TB) in last 3 years
Medical history indicative of an increased risk of arrhythmia.
Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Ppd Development, Lp
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.bms.com/studyconnect/pages/home.aspx
Description
BMS Clinical Trial Education Resource
URL
http://www.fda.gov/Safety/Recalls/
Description
FDA Safety Alerts and Recalls
Learn more about this trial
A Study to Assess the Effect of BMS-986142 on Pharmacokinetics (PK) of Probe Substrates
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