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

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

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

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: Itraconazole; Drug: BMS-986177; Drug: Diltiazem ER

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• Description BMS Clinical Trial Education Resource
• Description FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: June 17, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (Estimate): June 21, 2016

Study Record Updates

• Last Update Posted (Estimate): September 12, 2016
• Last Update Submitted That Met QC Criteria: September 9, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Antifungal Agents; Steroid Synthesis Inhibitors; Calcium Channel Blockers; 14-alpha Demethylase Inhibitors; Itraconazole; Diltiazem
• Other Study ID Numbers: CV010-005