A Open-label, Drug-Drug Interaction With Maraviroc (DDI)

A Phase 1, Open-label, Drug-drug Interaction Study Between BMS-663068 and Maraviroc in Healthy Subjects

This is a Phase 1, open-label, single sequence, two-way interaction study in healthy male and female subjects. For the effect of maraviroc on the pharmacokinetics (PK) of BMS-626529 (the active moiety of BMS-663068), there is no formal hypothesis to be statistically tested. The purpose of this assessment is to estimate the effect of maraviroc on the PK of BMS-626529 when coadministered in healthy subjects. For the effect of BMS-663068 on the PK of maraviroc, the hypothesis to be statistically tested is that BMS-663068 will not have a clinically significant effect on the PK of maraviroc when coadministered in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: BMS-663068; Drug: Maraviroc

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female nonsmoking subjects ages 18 to 50 years, inclusive with a body mass index of 18.0 to 32.0 kg/m2, inclusive
• Women of childbearing potential must agree to follow instructions for methods of contraception for a total of 34 days post-treatment completion

Exclusion Criteria:

• Any condition possibly affecting drug absorption
• Pre-existing liver dysfunction
• Any significant acute or chronic medical illness
• Orthostatic intolerance
• Other protocol specified exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential Dosing; Treatment A: BMS-663068 orally twice daily (BID) on Days 1 through 4 Treatment B: Maraviroc BID on Days 7 through 11 Treatment C: BMS-663068 BID plus maraviroc BID on Days 12 through 18	Drug: BMS-663068; BMS-663068; Drug: Maraviroc; Maraviroc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMS-626529 Pharmacokinetics: maximum observed plasma concentration (Cmax)	PK parameters for BMS-626529 in the absence or presence of multiple doses of maraviroc include: - Cmax	predose and up to 12 hours post dose on Days 4, 16, 17, and 18
BMS-626529 Pharmacokinetics: area under the plasma concentration-time curve (AUC) in a single dosing interval AUC(TAU)	PK parameters for BMS-626529 in the absence or presence of multiple doses of maraviroc include: - AUC(TAU)	predose and up to 12 hours post dose on Days 4, 16, 17, and 18
Maraviroc Pharmacokinetics: Cmax	PK parameters for maraviroc in the absence or presence of BMS-663068 include: - Cmax	predose and up to 12 hours post dose on Days 9, 10, 11, 16, 17, and 18
Maraviroc Pharmacokinetics: AUC(TAU)	PK parameters for maraviroc in the absence or presence of BMS-663068 include: - AUC(TAU)	predose and up to 12 hours post dose on Days 9, 10, 11, 16, 17, and 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other PK Parameters for BMS-626529: Time of maximum observed plasma concentration (Tmax)	PK parameters for BMS-626529 include: - Tmax	predose and up to 12 hours post dose on Days 4, 16, 17, and 18
Other PK Parameters for BMS-626529: plasma concentration observed at 12 hours post-dose (C12)	PK parameters for BMS-626529 include: - C12	predose and up to 12 hours post dose on Days 4, 16, 17, and 18
Other PK Parameters for BMS-626529: trough observed plasma concentration (Ctrough) (predose)	PK parameters for BMS-626529 include: - Ctrough (predose)	predose and up to 12 hours post dose on Days 4, 16, 17, and 18
Other PK Parameters for maraviroc: Tmax	PK Parameters for maraviroc include: -Tmax	predose and up to 12 hours post dose on Days 9, 10, 11, 16, 17, and 18
Other PK Parameters for maraviroc: C12	PK Parameters for maraviroc include: C12	predose and up to 12 hours post dose on Days 9, 10, 11, 16, 17, and 18
Other PK Parameters for maraviroc: Ctrough	PK Parameters for maraviroc include: - Ctrough	predose and up to 12 hours post dose on Days 9, 10, 11, 16, 17, and 18
Clinical Safety as Measured by Adverse Events	Adverse event monitoring	Day 1 to Day 26
Clinical Safety as Measured by Vital Signs	Vital sign measurement	Day 1 to Day 26
Clinical Safety as Measured by Electrocardiograms (ECGs)	12-lead ECGs	Day 1 to Day 26
Clinical Safety as Measured by Physical Examination	Physical examinations	Day 1 to Day 26
Clinical Safety as Measured by Clinical Laboratory Evaluations	Clinical chemistry, hematology, urinalysis	Day 1 to Day 26

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Wire MB, Magee M, Ackerman P, Llamoso C, Moore K. Evaluation of the pharmacokinetic drug-drug interaction between the antiretroviral agents fostemsavir and maraviroc: a single-sequence crossover study in healthy participants. HIV Res Clin Pract. 2021 Dec 9;23(1):1-8. Epub 2022 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2015
• Primary Completion (Actual): September 21, 2015
• Study Completion (Actual): September 21, 2015

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 20, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc; Fostemsavir
• Other Study ID Numbers: 206278; AI438-052 (Other Identifier: Bristol-Myers Squibb)