Drug-drug Interaction (DDI) Rifabutin

Pharmacokinetic Interaction Study to Evaluate the Pharmacokinetic Effect of Rifabutin on BMS-626529, the Active Moiety of BMS-663068, With and Without Ritonavir in Healthy Subjects

The purpose of this study is to provide dosing recommendations for the coadministration of BMS-663068 and Rifabutin with and without Ritonavir in upcoming Phase 3 studies and for prescribing information purposes

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

1. Signed Written Informed Consent

   a) Signed written informed consent must be obtained from the subjects in accordance with requirements of the study center's Institutional Review Board (IRB) or Independent Ethics Committee (IEC) before the initiation of any protocol-required procedures

2. Target Population

   • a) Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination findings, 12-lead ECG measurements, and clinical laboratory test results
   • b) Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive BMI = weight (kg)/[height (m)]2
   • c) Subject Reenrollment: This study permits the reenrollment of a subject that has discontinued the study as a pretreatment failure (ie, subject has not been randomized/has not been dosed). If reenrolled, the subject must be reconsented

3. Age and Reproductive Status

   • a) Men and women, ages 18 to 50 years, inclusive
   • b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
   • c) Women must not be breastfeeding
   • d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 half-lives of Rifabutin (13 days) plus 30 days (duration of ovulatory cycle) for a total of 43 days posttreatment completion
   • e) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 half-lives of Rifabutin (13 days) plus 90 days (duration of sperm turnover) for a total of 103 days posttreatment completion

Exclusion Criteria:

Medical History and Concurrent Diseases

• a) Any significant acute or chronic medical illness as determined by the Investigator.
• b) Current or recent (within 3 months of study drug administration) gastrointestinal disease
• c) Any major surgery within 4 weeks of study drug administration
• d) Any gastrointestinal surgery that could impact upon the absorption of study drug
• e) Intractable diarrhea (≥6 loose stools per day for at least 7 consecutive days) within 30 days prior to the first dose of study drug
• f) History of acute or chronic pancreatitis
• g) History of active or latent tuberculosis or any recent exposure to someone with tuberculosis
• h) History of uveitis and/or current eye or vision problems with the exception of corrective lenses
• i) Contact lens use during study drug administration or the need for contact lenses during study drug administration
• j) Donation of blood to a blood bank or in a clinical study (except screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma donation only)
• k) Blood transfusion within 4 weeks of study drug administration.
• l) History of any hemolytic disorders, including drug-induced hemolysis.
• m) Inability to tolerate oral medication
• n) Inability to be venipunctured and/or tolerate venous access
• o) Recent (within 6 months of study drug administration) history of smoking or current smokers
• p) Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV), Diagnostic Criteria for Drug and Alcohol Abuse
• q) Any other sound medical, psychiatric, and/or social reason as determined by the Investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BMS-663068 + Rifabutin; Regimen A: BMS-663068 tablet by mouth as specified Regimen B: BMS-663068 tablet with Rifabutin capsule by mouth as specified	Drug: BMS-663068; BMS-663068; Drug: Rifabutin; Rifabutin
Experimental: Cohort 2: BMS-663068 + Rifabutin + Ritonavir; Regimen A: BMS-663068 tablet by mouth as specified Regimen C: BMS-663068 tablet, Rifabutin capsule and Ritonavir (RTV) capsule by mouth as specified	Drug: BMS-663068; BMS-663068; Drug: Rifabutin; Rifabutin; Drug: Ritonavir; Ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration (Cmax) of BMS-626529	Day 2 to Day 15
Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-626529	Day 2 to Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum observed plasma concentration (Tmax) of BMS-626529	Day 2 to Day 15
Concentration at 12 hours after dosing (C12) of BMS-626529	Day 2 to Day 15
Trough observed plasma concentration (Ctrough) of BMS-626529 (predose)	Day 2 to Day 15
Safety and tolerability include incidence of adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, deaths, marked laboratory abnormalities, and abnormalities in vital signs, physical examination, and 12-lead electrocardiograms (ECGs)	Up to Day 30 after discontinuation of dose (approximately 45 days)

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2014
• Primary Completion (Actual): July 24, 2014
• Study Completion (Actual): July 24, 2014

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 21, 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; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Ritonavir; Rifabutin; Fostemsavir
• Other Study ID Numbers: 206282; AI438-041 (Other Identifier: Bristol-Myers Squibb)