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

NCT02807909 | Completed Phase 1

• 1 other identifier: CV010-005
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

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

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• 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.

Study Arms (2)

BMS-986177 and Itraconazole

EXPERIMENTAL

Single dose BMS-986177 on day 1 followed by Itraconazole and BMS-986177 on specified days

Drug: BMS-986177; Drug: Itraconazole

BMS-986177 and Diltiazem

EXPERIMENTAL

Single dose BMS-986177 on day 1 followed by Diltiazem ER and BMS-986177 on specified days

Drug: BMS-986177; Drug: Diltiazem ER

Interventions

BMS-986177 DRUG

BMS-986177 and Diltiazem; BMS-986177 and Itraconazole

Itraconazole DRUG

BMS-986177 and Itraconazole

Diltiazem ER DRUG

BMS-986177 and Diltiazem

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Related Publications (1)

• 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.

  PMID: 35641780 DERIVED

Related Links

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

MeSH Terms

Conditions

Thrombosis

Interventions

milvexian; Itraconazole

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: July 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 12, 2016

Record last verified: 2016-09