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Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00869557
First received: March 24, 2009
Last updated: December 10, 2012
Last verified: December 2012
History of Changes
Results First Received: September 20, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: HIV
HIV Infections
Interventions: Drug: Stribild
Drug: Atripla

  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
Participants were enrolled in a total of 30 sites in the United States. The first participant was screened on 30 March 2009. The last participant visit (LPV) for the primary endpoint analysis (Week 24) was in November 2009; LPV for the Week 48 analysis was in May 2010; LPV for the Week 96 analysis was in May 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
126 participants were screened; 71 were randomized (48 to the Stribild group and 23 to the Atripla group). All randomized participants received at least 1 dose of study medication and comprised the safety and intent-to-treat (ITT) analysis sets. No site enrolled more than 7% of participants.

Reporting Groups
  Description
Stribild Stribild (elvitegravir [EVG] 150 mg/GS-9350 [cobicistat; COBI] 150 mg/emtricitabine [FTC] 200 mg/tenofovir disoproxil fumarate [TDF] 300 mg) once daily (QD) and placebo to match Atripla once daily prior to bedtime (QHS) were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla (efavirenz [EFV] 150 mg/FTC 200 mg/TDF 300 mg) QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Participant Flow for 2 periods

 Period 1:   Randomized Phase
    Stribild     Atripla  
STARTED     48     23  
COMPLETED     45     20  
NOT COMPLETED     3     3  
Adverse Event                 0                 1  
Lost to Follow-up                 2                 1  
Withdrawal by Subject                 0                 1  
Physician Decision                 1                 0  

Period 2:   Extension Phase
    Stribild     Atripla  
STARTED     45     14 [1]
COMPLETED     0     0  
NOT COMPLETED     45     14  
Adverse Event                 1                 1  
Physician Decision                 2                 0  
Lost to Follow-up                 0                 1  
Subjects Still on Study Treatment                 42                 12  
[1] Six participants completing randomized Atripla treatments did not enter open-label extension phase



  Baseline Characteristics
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Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.
Total Total of all reporting groups

Baseline Measures
    Stribild     Atripla     Total  
Number of Participants  
[units: participants]
 		  48     23     71  
Age  
[units: participants]
 		     
<=18 years     0     0     0  
Between 18 and 65 years     48     23     71  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation 		  36  ± 8.9     35  ± 9.6     36  ± 9.1  
Gender  
[units: participants]
 		     
Female     4     2     6  
Male     44     21     65  
Race/Ethnicity, Customized  
[units: participants]
 		     
American Indian or Alaska Native     1     0     1  
Asian     1     0     1  
Black     12     5     17  
White     33     18     51  
Other     1     0     1  
Region of Enrollment  
[units: participants]
 		     
United States     48     23     71  
HIV Disease Status  
[units: participants]
 		     
Asymptomatic     40     22     62  
Symptomatic HIV Infections     5     0     5  
AIDS     3     1     4  
Hepatitis B Virus (HBV) Infection Status  
[units: participants]
 		     
Negative     48     23     71  
Positive     0     0     0  
Hepatitis C Virus (HCV) Infection Status  
[units: participants]
 		     
Negative     48     23     71  
Positive     0     0     0  
HIV-1 RNA Category (copies/mL)  
[units: participants]
 		     
≤ 100,000     37     18     55  
> 100,000     11     5     16  
Cluster Determinant 4 (CD4) Cell Count (/µL)  
[units: participants]
 		     
≤ 50     0     0     0  
51 to ≤ 200     7     0     7  
201 to ≤ 350     17     8     25  
351 to ≤ 500     14     5     19  
> 500     10     10     20  



  Outcome Measures
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1.  Primary:   The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24   [ Time Frame: Week 24 ]

Measure Type Primary
Measure Title The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24
Measure Description The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.
Time Frame Week 24  
Safety Issue No  

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.
ITT analysis set (all participants who were randomized into the study and received at least 1 dose of study drug). The missing = failure (M = F) analysis method was used in which all missing data were considered as failure (HIV-1 RNA ≥ 50 copies/mL).

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  48     23  
The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24  
[units: percentage of participants]
 		  89.6     87.0  


Statistical Analysis 1 for The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Difference in the response rates (%) [3] 2.8
95% Confidence Interval ( -14.5 to 20.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypothesis was that the response rate (proportion of participants with HIV-1 RNA < 50 copies/mL at Week 24) in the Stribild group was at least 12% worse than the response rate in Atripla group; the alternative hypothesis was that the response rate in the Stribild group was less than 12% worse than that in the Atripla group.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
 

A total sample size of 75 participants randomized in a 2:1 ratio had 26% power to evaluate noninferiority with respect to the response rate of HIV-1 RNA < 50 copies/mL at Week 24 if a response rate of 84% for both treatment groups and a noninferiority margin of 0.12 were assumed.

A total of 71 participants were enrolled in the study (4 fewer than planned).
[3] Other relevant estimation information:
  The 95% confidence interval was computed using normal approximation stratified by baseline HIV-1 RNA stratum (≤ 100,000 or > 100,000 copies/mL).



2.  Secondary:   The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
Measure Description The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.
Time Frame Week 48  
Safety Issue No  

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.
ITT analysis set; M = F analysis (all missing data were considered as failure [HIV-1 RNA ≥ 50 copies/mL]).

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  48     23  
The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48  
[units: percentage of participants]
 		  89.6     87.0  

No statistical analysis provided for The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48



3.  Secondary:   Change From Baseline in HIV-1 RNA (log_10 Copies/mL)   [ Time Frame: Baseline to Weeks 24 and 48 ]

Measure Type Secondary
Measure Title Change From Baseline in HIV-1 RNA (log_10 Copies/mL)
Measure Description Change = Week 24 or 48 value minus baseline value
Time Frame Baseline to Weeks 24 and 48  
Safety Issue No  

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.
ITT analysis set; The missing = excluded (M = E) analysis method was used in which all missing data were excluded from the analysis.

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  45     21  
Change From Baseline in HIV-1 RNA (log_10 Copies/mL)  
[units: log_10 copies/mL]
Mean ± Standard Deviation 		   
Baseline to Week 24     -2.87  ± 0.578     -2.88  ± 0.586  
Baseline to Week 48     -2.89  ± 0.570     -2.71  ± 0.933  

No statistical analysis provided for Change From Baseline in HIV-1 RNA (log_10 Copies/mL)



4.  Secondary:   Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24   [ Time Frame: Baseline to Week 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24
Measure Description Change = Week 24 value minus baseline value
Time Frame Baseline to Week 24  
Safety Issue No  

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.
ITT analysis set. M = E analysis (all missing data were excluded from the analysis).

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  44     21  
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24  
[units: cells/µL]
Mean ± Standard Deviation 		  161  ± 141.1     117  ± 143.7  

No statistical analysis provided for Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24



5.  Secondary:   Change From Baseline in CD4 Cell Count at Week 48   [ Time Frame: Baseline to Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in CD4 Cell Count at Week 48
Measure Description Change = Week 48 value minus baseline value
Time Frame Baseline to Week 48  
Safety Issue No  

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.
ITT analysis set; M = E analysis (all missing data were excluded from the analysis).

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  45     21  
Change From Baseline in CD4 Cell Count at Week 48  
[units: cells/µL]
Mean ± Standard Deviation 		  240  ± 172.8     166  ± 158.5  

No statistical analysis provided for Change From Baseline in CD4 Cell Count at Week 48



6.  Secondary:   The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL   [ Time Frame: Baseline to Weeks 24 and 48 ]

Measure Type Secondary
Measure Title The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL
Measure Description The percentage of participants with virologic success at Weeks 24 and 48 assessed using the FDA-defined snapshot analysis for an HIV-1 RNA cutoff of 50 copies/mL was summarized.
Time Frame Baseline to Weeks 24 and 48  
Safety Issue No  

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.
ITT analysis set

Reporting Groups
  Description
Stribild Stribild QD and placebo to match Atripla QHS were administered during the double-blind phase. Stribild QD was administered during the extension phase.
Atripla Atripla QHS and placebo to match Stribild QD were administered during the double blind phase. Stribild QD was administered during the extension phase.

Measured Values
    Stribild     Atripla  
Number of Participants Analyzed  
[units: participants]
 		  48     23  
The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL  
[units: percentage of participants]
 		   
Virologic Success at Week 24     89.6     87.0  
Virologic Success at Week 48     91.7     82.6  

No statistical analysis provided for The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL




  Serious Adverse Events
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  Other Adverse Events
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  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.


Limitations and Caveats
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.  


Results Point of Contact:  
Name/Title: Christophe Beraud, Director, Regulatory Affairs
Organization: Gilead Sciences, Inc
phone: (650) 522-5093
e-mail: christophe.beraud@gilead.com


Publications of Results:


Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00869557     History of Changes
Other Study ID Numbers: GS-US-236-0104
Study First Received: March 24, 2009
Results First Received: September 20, 2012
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration