Clinical trial NCT02807909: A Study to Evaluate the Effect of Co-administration of Itraconazole or Diltiazem on the Pharmacokinetics of BMS-986177 in Healthy Subjects
Official title: An Open-Label Single-Sequence Study to Evaluate the Effect of Co-administration of Itraconazole or Diltiazem on the Single-Dose Pharmacokinetics of BMS-986177 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombosis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-06-21
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The study is being conducted to assess the effects of co-administration of itraconazole or diltiazem, respectively, on the pharmacokinetic (PK) parameters Cmax, AUC(INF), and AUC(0-T) of BMS-986177


Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent
2. Target population: Healthy 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 30 kg/m2, inclusive
4. Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and are not breast feeding
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 92 days for subjects in the BMS-986177 - diltiazem sequence, and 99 days for subjects in the BMS-986177 - itraconazole sequence.

Exclusion Criteria:

1. Any significant acute or chronic medical illness, including hepatic disease, or any other condition listed as a contraindication in the diltiazem or itraconazole package inserts.
2. Evidence of coagulopathy, prolonged or unexplained clinically significant bleeding, or frequent unexplained bruising or thrombus formation.
3. History of chronic constipation, GI disease, arrhythmias, sinus bradycardia, significant head injury, dizziness or headaches, hemophilia, Rosenthal syndrome, or FX1a deficiency or other coagulopathies, systemic lupus erythematosus.
4. 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
5. History of allergy to BMS-986177, itraconazole, diltiazem, or related compounds.

Primary outcomes:
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC (0-T)) of BMS-986177
timeFrame: Days 1-12
measure: Maximum observed concentration (Cmax)
timeFrame: Days 1-12
measure: Area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
timeFrame: Days 1-12
Secondary outcomes:
measure: Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death
timeFrame: Screening- until 30 days after discontinuation of dosing or subject's participation in the study if the last scheduled visit occurs at a later time.
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Perera V, Wang Z, Lubin S, Christopher LJ, Chen W, Xu S, Seiffert D, DeSouza M, Murthy B. Effects of Itraconazole and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Milvexian, A Factor XIa Inhibitor. Cardiol Ther. 2022 Sep;11(3):407-419. doi: 10.1007/s40119-022-00266-6. Epub 2022 May 31.