Clinical trial NCT02762123: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-05-04
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent
2. Target population: Healthy (current non-smokers) subjects as determined by medical history, surgical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory determinations.
3. Subjects with body mass index of 18 to 32 kg/m2, inclusive
4. Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and must not be breastfeeding.
5. 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:

1. 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.
2. History of billiary disorder, asthma, bleeding disorder, cancer
3. Received live vaccine during last 12 weeks, active tuberculosis (TB) in last 3 years
4. Medical history indicative of an increased risk of arrhythmia.
5. 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.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin.
timeFrame: 57 samples up to day 26
measure: 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
timeFrame: 57 samples up to day 26
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin
timeFrame: 57 samples up to day 26
Secondary outcomes:
measure: Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death
timeFrame: Days 1-26; for SAEs up to 30 days post discontinuation of dosing
Other outcomes:
Locations:
city: Austin
country: United States
facility: Ppd Development, Lp
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: