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

Study Overview
=================
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

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

Conditions
-----------------
Thrombosis

Intervention / Treatment
-----------------
* Drug: BMS-986177
* Drug: Itraconazole
* Drug: Diltiazem ER


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed Consent Target population: Healthy 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 30 kg/m2, inclusive Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and are not breast feeding 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: 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. Evidence of coagulopathy, prolonged or unexplained clinically significant bleeding, or frequent unexplained bruising or thrombus formation. 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. 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 History of allergy to BMS-986177, itraconazole, diltiazem, or related compounds.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986177 and Itraconazole<br>Single dose BMS-986177 on day 1 followed by Itraconazole and BMS-986177 on specified days | Drug: BMS-986177<br> <br> Drug: Itraconazole<br> <br> |
| Experimental: BMS-986177 and Diltiazem<br>Single dose BMS-986177 on day 1 followed by Diltiazem ER and BMS-986177 on specified days | Drug: BMS-986177<br> <br> Drug: Diltiazem ER<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |