A Study to Evaluate the Effect of Co-administration of Itraconazole or Diltiazem on the Pharmacokinetics of BMS-986177 in Healthy Subjects

Phase 1

Completed

• Conditions: Thrombosis
• Interventions: Drug: BMS-986177; Drug: Itraconazole; Drug: Diltiazem ER

• Registration Number: NCT02807909
• Lead Sponsor: Bristol-Myers Squibb

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-17
• Study First Submitted QC: 2016-06-17
• Study First Posted: 2016-06-21
• Study Start: 2016-07
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-09
• Last Update Posted: 2016-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BMS-986177 and Itraconazole	BMS-986177	Single dose BMS-986177 on day 1 followed by Itraconazole and BMS-986177 on specified days
BMS-986177 and Itraconazole	Itraconazole	Single dose BMS-986177 on day 1 followed by Itraconazole and BMS-986177 on specified days
BMS-986177 and Diltiazem	BMS-986177	Single dose BMS-986177 on day 1 followed by Diltiazem ER and BMS-986177 on specified days
BMS-986177 and Diltiazem	Diltiazem ER	Single dose BMS-986177 on day 1 followed by Diltiazem ER and BMS-986177 on specified days

Primary Outcome Measures

Name	Time	Method
Maximum observed concentration (Cmax)	Days 1-12
Area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF))	Days 1-12
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC (0-T)) of BMS-986177	Days 1-12

Secondary Outcome Measures

Name	Time	Method
Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death	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.