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

Primary Purpose

Thrombosis

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

BMS-986177

Itraconazole

Diltiazem ER

About this trial

This is an interventional basic science trial for Thrombosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

BMS-986177 and Itraconazole

BMS-986177 and Diltiazem

Arm Description

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

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

Outcomes

Primary Outcome Measures

Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC (0-T)) of BMS-986177

Maximum observed concentration (Cmax)

Area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF))

Secondary Outcome Measures

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

Full Information

NCT ID

NCT02807909

First Posted

June 17, 2016

Last Updated

September 9, 2016

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT02807909

Brief Title

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

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

July 2016 (undefined)

Primary Completion Date

August 2016 (Actual)

Study Completion Date

August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombosis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BMS-986177 and Itraconazole

Arm Type

Experimental

Arm Description

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

Arm Title

BMS-986177 and Diltiazem

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

BMS-986177

Intervention Type

Drug

Intervention Name(s)

Itraconazole

Intervention Type

Drug

Intervention Name(s)

Diltiazem ER

Primary Outcome Measure Information:

Title

Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC (0-T)) of BMS-986177

Time Frame

Days 1-12

Title

Maximum observed concentration (Cmax)

Time Frame

Days 1-12

Title

Area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF))

Time Frame

Days 1-12

Secondary Outcome Measure Information:

Title

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

Time Frame

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

35641780

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.

Results Reference

derived

Links:

URL

http://www.bms.com/studyconnect/pages/home.aspx

Description

Description BMS Clinical Trial Education Resource

URL

http://www.fda.gov/Safety/Recalls/

Description

Description FDA Safety Alerts and Recalls

Learn more about this trial

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

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