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Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat

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 19, 2014
Last verified: August 2014
Results First Received: June 9, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Bio-equivalence Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
Condition: Human Immunodeficiency Virus Type 1 (HIV-1)
Interventions: Drug: Atazanavir
Drug: Cobicistat
Drug: Atazanavir/Cobicistat FDC

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 149 patients were enrolled and 64 randomized to 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC), with a 7-day washout period between treatments. Approximately 32 were to be discharged after Period 4, based on treatment sequence. Those remaining were to continue to and be discharged at end of Period 5.

Reporting Groups
  Description
All Participants Who Received Treatment All participants who received atazanavir with cobicistat in 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC). Treatment A: Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat, 150 mg as tablet, following a light meal on Day 1 or 8. Treatment B: Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8. Treatment C: Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day15 or 22. Treatment D: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22. Treatment E: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29.

Participant Flow for 5 periods

Period 1:   Period 1: Days 1-7 (Treatment A or B)
    All Participants Who Received Treatment  
STARTED     64 [1]
COMPLETED     64  
NOT COMPLETED     0  
[1] Received treatment

Period 2:   Period 2: Days 8-14 (Treatment B or A)
    All Participants Who Received Treatment  
STARTED     64  
COMPLETED     63  
NOT COMPLETED     1  
Withdrawal by Subject                 1  

Period 3:   Period 3: Days 15-21 (Treatment C or D)
    All Participants Who Received Treatment  
STARTED     63  
COMPLETED     63  
NOT COMPLETED     0  

Period 4:   Period 4: Days 22-28 (Treatment D or C)
    All Participants Who Received Treatment  
STARTED     63  
COMPLETED     63 [1]
NOT COMPLETED     0  
[1] Number finishing period; 32 patients were discharged following Period 4, as per protocol

Period 5:   Period 5: Days 29-31 (Treatment E)
    All Participants Who Received Treatment  
STARTED     31 [1]
COMPLETED     30  
NOT COMPLETED     1  
Poor compliance/noncompliance                 1  
[1] Reflects the 31 patients remaining after 32 were discharged at the end of Period 4, as per protocol



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug

Reporting Groups
  Description
All Participants Who Received Treatment All participants who received atazanavir with cobicistat in 1 of 8 treatment sequences (ABCDE, ABDCE, BACDE, BADCE, ABCD, ABDC, BACD, or BADC). Treatment A: Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, following a light meal on Day 1 or 8. Treatment B: Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8. Treatment C: Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day 15 or 22. Treatment D: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day15 or 29. Treatment E: Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29.

Baseline Measures
    All Participants Who Received Treatment  
Number of Participants  
[units: participants]
  64  
Age  
[units: Years]
Mean ± Standard Deviation
  32.5  ± 7.4  
Gender  
[units: Participants]
 
Female     24  
Male     40  
Race/Ethnicity, Customized  
[units: Participants]
 
White     29  
Black     33  
Asian     2  
Body mass index  
[units: kg/m^2]
Mean ± Standard Deviation
  26.5  ± 2.9  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Observed Plasma Concentration (Cmax) of Atazanavir   [ Time Frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose) ]

2.  Primary:   Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and From Time 0 to Infinity (AUC[INF]) for Atazanavir   [ Time Frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose) ]

3.  Secondary:   Number of Participants Who Died and With Serious Adverse Events (SAEs)   [ Time Frame: On Day 24 or 31 ]

4.  Secondary:   Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests   [ Time Frame: At Screening and on Days -1,4, 11, 18, and 31 (study discharge) ]

5.  Secondary:   Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings   [ Time Frame: At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31) ]

6.  Secondary:   Time of Maximum Observed Concentration (Tmax) of Atazanavir   [ Time Frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose) ]

7.  Secondary:   Observed Concentration at 24 Hours (C24) of Atazanavir   [ Time Frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose) ]

8.  Secondary:   Apparent Terminal Half-life (T-HALF) of Atazanavir   [ Time Frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose) ]

9.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Cobicistat   [ Time Frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose) ]

10.  Secondary:   Time of Maximum Observed Concentration (Tmax) of Cobicistat   [ Time Frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose) ]

11.  Secondary:   Area Under the Concentration Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and Area Under the Concentration Curve From Time 0 to Infinity (AUC[INF]) of Cobicistat   [ Time Frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose) ]

12.  Secondary:   T-HALF of Cobicistat   [ Time Frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


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
Results First Received: June 9, 2014
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration