Bioequivalence (BE) Study of Individual Atazanavir and Cobicistat Compared to Atazanavir in Fixed Dose Combination With Cobicistat (AtazanavirBE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01837719
First received: April 18, 2013
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

The purpose of the study is to evaluate the comparability of Atazanavir in a fixed dose combination with Atazanavir co-administered with Cobicistat as single agents.


Condition Intervention Phase
Human Immunodeficiency Virus Type 1 (HIV-1)
Drug: Atazanavir
Drug: Cobicistat
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Randomized, 5-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Following a Light Meal, the Relative Bioavailability of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Under Fasted Conditions, and the Effect of Food on the Bioavailability of Atazanavir in the Fixed Dose Combination

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Systemic exposure to Atazanavir (ATV) measured as maximum observed plasma concentration (Cmax) [ Time Frame: 11 timepoints on Day 1 ] [ Designated as safety issue: No ]
  • Systemic exposure to ATV measured as Cmax [ Time Frame: 11 timepoints on Day 8 ] [ Designated as safety issue: No ]
  • Systemic exposure to ATV measured as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] [ Time Frame: 11 timepoints on Day 1 ] [ Designated as safety issue: No ]
  • Systemic exposure to ATV measured as AUC(0-T) [ Time Frame: 11 timepoints on Day 8 ] [ Designated as safety issue: No ]
  • Systemic exposure to ATV measured as area under the plasma concentration-time curve from time zero extrapolated to infinity [AUC(INF)] [ Time Frame: 11 timepoints on Day 1 ] [ Designated as safety issue: No ]
  • Systemic exposure to ATV measured as AUC(INF) [ Time Frame: 11 timepoints on Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety will be measured by incidence of adverse events (AEs), serious AEs, AEs leading to discontinuations and deaths, and marked abnormalities in clinical laboratory tests, vital signs and electrocardiogram (ECG) measurements [ Time Frame: On Day 24 or 31 ] [ Designated as safety issue: Yes ]
  • Time of maximum observed concentration (Tmax) of ATV [ Time Frame: 11 timepoints on Days 1, 8, 15, 22 and 29 ] [ Designated as safety issue: No ]
  • AUC(0-T) of ATV [ Time Frame: 11 timepoints on Days 15, 22 and 29 ] [ Designated as safety issue: No ]
  • Observed concentration at 24 hour (C24) after ATV dose [ Time Frame: 11 timepoints on Days 1, 8, 15, 22 and 29 ] [ Designated as safety issue: No ]
  • Apparent terminal half-life (T-HALF) of ATV [ Time Frame: 11 timepoints on Days 1, 8, 15, 22 and 29 ] [ Designated as safety issue: No ]
  • Cmax of ATV [ Time Frame: 11 timepoints on Days 15, 22 and 29 ] [ Designated as safety issue: No ]
  • AUC(INF) of ATV [ Time Frame: 11 timepoints on Days 15, 22 and 29 ] [ Designated as safety issue: No ]
  • Cmax of Cobicistat [ Time Frame: 12 timepoints on 1, 2, 8, 9, 15, 16, 22 23, 29 and 30 ] [ Designated as safety issue: No ]
  • Tmax of Cobicistat [ Time Frame: 12 timepoints on 1, 2, 8, 9, 15, 16, 22 23, 29 and 30 ] [ Designated as safety issue: No ]
  • AUC(0-T) of Cobicistat [ Time Frame: 12 timepoints on 1, 2, 8, 9, 15, 16, 22 23, 29 and 30 ] [ Designated as safety issue: No ]
  • AUC(INF) of Cobicistat [ Time Frame: 12 timepoints on 1, 2, 8, 9, 15, 16, 22 23, 29 and 30 ] [ Designated as safety issue: No ]
  • T-HALF of Cobicistat [ Time Frame: 12 timepoints on 1, 2, 8, 9, 15, 16, 22 23, 29 and 30 ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: April 2013
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Atazanavir + Cobicistat co-administered
Co-administration of single dose of Atazanavir 300 mg capsule and Cobicistat 150 mg tablet given by mouth following a light meal on Days 1, 8, 15, 22
Drug: Atazanavir
Other Name: BMS-232632
Drug: Cobicistat
Experimental: Arm B: Atazanavir/Cobicistat fixed dose combination
Administration of single fixed dose of combination of Atazanavir 300 mg capsule / Cobicistat 150 mg tablet given by mouth following a light meal on Days 1, 8, 15, 22 and 29
Drug: Atazanavir
Other Name: BMS-232632
Drug: Cobicistat
Experimental: Arm C: Atazanavir + Cobicistat co-administered
Co-administration of single dose of Atazanavir 300 mg capsule and Cobicistat 150 mg tablet given by mouth under fasted conditions on Days 1, 8, 15 and 22
Drug: Atazanavir
Other Name: BMS-232632
Drug: Cobicistat
Experimental: Arm D: Atazanavir/Cobicistat fixed dose combination
Administration of single fixed dose of combination of Atazanavir 300 mg capsule / Cobicistat 150 mg tablet given by mouth under fasted conditions on Days 1, 8, 15, 22 and 29
Drug: Atazanavir
Other Name: BMS-232632
Drug: Cobicistat
Experimental: Arm E: Atazanavir/Cobicistat fixed dose combination
Administration of single fixed dose of combination of Atazanavir 300 mg capsule / Cobicistat 150 mg tablet given by mouth following a high fat meal on Days 1, 8, 15, 22 and 29
Drug: Atazanavir
Other Name: BMS-232632
Drug: Cobicistat

Detailed Description:

Primary Purpose: Atazanavir is a marketed product and this study is to evaluate the single-dose pharmacokinetics and bioequivalence of Atazanavir when administered as a fixed dose combination relative to the commercial capsule formulation, co-administered with Cobicistat.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men and women of ages 18 to 49 and BMI 18 to 32 kg/m2, inclusive
  • Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding
  • WOCBP and men who are sexually active with WOCBP must use acceptable contraceptive methods

Exclusion Criteria:

  • Any significant acute or chronic medical illness
  • Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat

    1. PR ≥210 msec
    2. QRS ≥120 msec
    3. QT ≥500 msec
    4. QTcF ≥450 msec
  • Positive urine screen for drugs of abuse
  • Second or third degree A-V block or clinically relevant ECG abnormalities
  • Any of the following laboratory results outside of the ranges specified below:

    1. Alanine aminotransferase (ALT) >upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST) >ULN
    3. Total bilirubin >ULN
    4. Serum creatinine >ULN
  • Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibodies
  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 ClinicalTrials.gov identifier: NCT01837719

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

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01837719     History of Changes
Other Study ID Numbers: AI424-511
Study First Received: April 18, 2013
Last Updated: August 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Atazanavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014