Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Drug-drug Interaction (DDI) Rifabutin

This study has been completed.
Information provided by (Responsible Party):
Bristol-Myers Squibb Identifier:
First received: May 13, 2014
Last updated: September 10, 2014
Last verified: September 2014

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

Condition Intervention Phase
Drug: BMS-663068
Drug: Rifabutin
Drug: Ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) of BMS-626529 [ Time Frame: Day 2 to Day 15 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-626529 [ Time Frame: Day 2 to Day 15 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time of maximum observed plasma concentration (Tmax) of BMS-626529 [ Time Frame: Day 2 to Day 15 ] [ Designated as safety issue: No ]
  • Concentration at 12 hours after dosing (C12) of BMS-626529 [ Time Frame: Day 2 to Day 15 ] [ Designated as safety issue: No ]
  • Trough observed plasma concentration (Ctrough) of BMS-626529 (predose) [ Time Frame: Day 2 to Day 15 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Up to Day 30 after discontinuation of dose (approximately 45 days) ] [ Designated as safety issue: Yes ]

Enrollment: 46
Study Start Date: May 2014
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Drug: 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 Drug: Rifabutin Drug: Ritonavir


Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

For more information regarding BMS clinical trial participation, please visit

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02138084

United States, Texas
Ppd Development, Lp
Austin, Texas, United States, 78744
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb Identifier: NCT02138084     History of Changes
Other Study ID Numbers: AI438-041
Study First Received: May 13, 2014
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antibiotics, Antitubercular
Antitubercular Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses processed this record on February 25, 2015