DDI Study of BMS-663068 With Etravirine (ETR) and/or Darunavir (DVR) + Ritonavir (RTV)

Open-Label, Single-Sequence Study to Evaluate the Pharmacokinetic Interaction of BMS-663068 With Darunavir/Ritonavir and/or Etravirine in Healthy Subjects

The purpose of this study is to determine if there is an interaction in healthy subjects taking BMS-663068 with Darunavir/Ritonavir and/or Etravirine.

Study Overview

• Status: Completed
• Conditions: Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: BMS-663068; Drug: Darunavir (DRV); Drug: Ritonavir (RTV); Drug: Etravirine (ETR)

Detailed Description

Brief title: drug-drug interaction (DDI)

Primary Purpose: Other : Phase 1 Clinical Pharmacology drug interaction study in healthy subjects

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

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 subjects with no clinically significant deviation from normal in medical history, physical examination findings, 12-lead ECG measurements, and clinical laboratory tests
• Women of childbearing potential (WOCBP) allowed. Must be practicing highly effective methods of contraception

Exclusion Criteria:

• Any significant acute or chronic medical condition
• Unable to tolerate oral medications
• Inability to be venipunctured and/or tolerate venous access
• Current or recent (within 3 months of dosing) gastrointestinal disease
• Abnormal liver function test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BMS-663068+DRV/RTV; Extended release tablet BMS-663068 600mg orally twice daily on days 1-4 and 17-26. Tablet DRV 600mg / RTV 100mg orally orally twice daily on days 7-16	Drug: BMS-663068; BMS-663068; Drug: Darunavir (DRV); Darunavir (DRV); Other Names: Prezista; Drug: Ritonavir (RTV); Ritonavir (RTV); Other Names: Norvir
Experimental: Cohort 2: BMS-663068+ETR; Extended release tablet BMS-663068 600mg orally twice daily on days 1-4 and 17-26. Tablet ETR 200mg orally orally twice daily on days 7-16	Drug: BMS-663068; BMS-663068; Drug: Etravirine (ETR); Etravirine (ETR); Other Names: Intelence
Experimental: Cohort 3: BMS-663068+DRV/RTV+ETR; Extended release tablet BMS-663068 600mg orally twice daily on days 1-4 and 17-26. Tablet DRV 600mg / RTV 100mg and ETR 200mg orally orally twice daily on days 7-16	Drug: BMS-663068; BMS-663068; Drug: Darunavir (DRV); Darunavir (DRV); Other Names: Prezista; Drug: Ritonavir (RTV); Ritonavir (RTV); Other Names: Norvir; Drug: Etravirine (ETR); Etravirine (ETR); Other Names: Intelence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration (Cmax) of BMS-626529	20 timepoints up to day 26
Area under the concentration-time curve in 1 dosing interval (AUC(TAU)) of BMS-626529	20 timepoints up to day 26

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum observed plasma concentration (Tmax) for BMS-626529, DRV, RTV, and ETR	Up to day 26 (20 timepoints for BMS-626529, 24 timepoints for DRV, RTV and ETR)
Concentration at 12 hours (C12) for BMS-626529, DRV, RTV, and ETR	Up to day 26 (20 timepoints for BMS-626529, 24 timepoints for DRV, RTV and ETR)
Trough observed plasma concentration (Ctrough) for BMS-626529, DRV, RTV, and ETR	Up to day 26 (20 timepoints for BMS-626529, 24 timepoints for DRV, RTV and ETR)
Cmax for DRV, RTV, and ETR	24 timepoints up to 26 day
AUC(TAU) for DRV, RTV, and ETR	24 timepoints up to 26 day
Safety and tolerability endpoints include incidence of adverse event (AEs), serious adverse event (SAEs), AEs leading to discontinuation, deaths, marked laboratory abnormalities, and abnormalities in vital signs, physical examination, and 12-lead ECGs	Up to day 27

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Moore K, Thakkar N, Magee M, Sevinsky H, Vakkalagadda B, Lubin S, Llamoso C, Ackerman P. Pharmacokinetics of Temsavir, the Active Moiety of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir, Coadministered with Cobicistat, Etravirine, Darunavir/Cobicistat, or Darunavir/Ritonavir with or without Etravirine in Healthy Participants. Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0225121. doi: 10.1128/aac.02251-21. Epub 2022 Mar 22.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 13, 2014

Study Registration Dates

• First Submitted: February 13, 2014
• First Submitted That Met QC Criteria: February 13, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): August 8, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 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; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Ritonavir; Darunavir; Etravirine; Fostemsavir
• Other Study ID Numbers: 206281; AI438-020 (Other Identifier: Bristol-Myers Squibb)