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Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01106586
First received: April 14, 2010
Last updated: October 23, 2014
Last verified: October 2014
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: ATV/r + FTC/TDF

  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 at 146 sites in 16 countries. The first participant was screened on 06 April 2010. The last participant observation for the Week 144 analysis was on 09 August 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1017 subjects were screened and 715 were randomized. 708 randomized participants received at least 1 dose of study medication and comprise the Safety Analysis Set and the Intent-to-Treat (ITT) Analysis Set.

Reporting Groups
  Description
Stribild Stribild (elvitegravir [EVG] 150 mg/cobicistat [COBI] 150 mg/emtricitabine [FTC] 200 mg/tenofovir disoproxil fumarate [TDF] 300 mg) plus placebo to match atazanavir/ritonavir (ATV/r) + FTC/TDF once daily
ATV/r + FTC/TDF ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily

Participant Flow:   Overall Study
    Stribild     ATV/r + FTC/TDF  
STARTED     353     355  
COMPLETED     0     0  
NOT COMPLETED     353     355  
Adverse Event                 8                 14  
Death                 1                 3  
Pregnancy                 1                 1  
Lack of Efficacy                 1                 0  
Investigator's Discretion                 3                 5  
Withdrew Consent                 12                 18  
Lost to Follow-up                 20                 16  
Subject Noncompliance                 12                 9  
Protocol Violation                 1                 0  
Subject Still on Study Treatment                 255                 259  
Subject Joined Other Study                 39                 30  



  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.
No text entered.

Reporting Groups
  Description
Stribild Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily
ATV/r + FTC/TDF ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily
Total Total of all reporting groups

Baseline Measures
    Stribild     ATV/r + FTC/TDF     Total  
Number of Participants  
[units: participants]
  353     355     708  
Age  
[units: years]
Mean ± Standard Deviation
  38  ± 10.5     39  ± 9.8     38  ± 10.2  
Gender  
[units: participants]
     
Female     29     39     68  
Male     324     316     640  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     2     3     5  
Asian     17     17     34  
Black or African Heritage     72     47     119  
Native Hawaiian or Pacific Islander     1     2     3  
White     250     277     527  
Other     11     9     20  
Region of Enrollment  
[units: participants]
     
Portugal     1     2     3  
United States     197     185     382  
Thailand     7     4     11  
Austria     12     8     20  
United Kingdom     11     15     26  
Switzerland     0     2     2  
Italy     9     5     14  
France     23     23     46  
Mexico     3     2     5  
Canada     19     22     41  
Belgium     9     12     21  
Australia     30     32     62  
Denmark     1     2     3  
Netherlands     2     4     6  
Germany     29     36     65  
Sweden     0     1     1  
HIV Disease Status  
[units: participants]
     
Asymptomatic     285     293     578  
Symptomatic HIV Infections     36     38     74  
AIDS     32     24     56  
Hepatitis B Virus (HBV) Infection Status  
[units: participants]
     
Negative     347     346     693  
Positive     5     7     12  
Indeterminate     0     1     1  
Not done     1     1     2  
Hepatitis C Virus (HCV) Infection Status  
[units: participants]
     
Negative     335     344     679  
Positive     18     10     28  
Indeterminate     0     0     0  
Not done     0     1     1  
HIV-1 RNA Category (copies/mL)  
[units: participants]
     
≤ 100,000     203     214     417  
> 100,000     150     141     291  
CD4 Cell Count (/µL)  
[units: participants]
     
≤ 50     12     5     17  
51 to ≤ 200     42     34     76  
201 to ≤ 350     122     124     246  
351 to ≤ 500     122     122     244  
> 500     55     70     125  



  Outcome Measures
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1.  Primary:   The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
Measure Description No text entered.
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: participants who were randomized into the study and received at least 1 dose of study drug

Reporting Groups
  Description
Stribild Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) plus placebo to match ATV/r + FTC/TDF once daily
ATV/r + FTC/TDF ATV/r 300/100 mg tablet plus FTC 200 mg/TDF 300 mg tablet plus placebo to match Stribild once daily

Measured Values
    Stribild     ATV/r + FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  353     355  
The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48  
[units: percentage¬†of¬†participants]
  89.5     86.8  


Statistical Analysis 1 for The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Difference in response rates [3] 3.0
95.2% Confidence Interval ( -1.9 to 7.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypothesis was that the Stribild group is at least 12% worse than the ATV/r + Truvada group with respect to percentage of participants achieving HIV-1 RNA < 50 copies/mL (response rate as defined by the snapshot analysis algorithm) at Week 48; the alternative hypothesis was that the response rate in the Stribild group is less than 12% worse than that in the ATV/r + Truvada Group.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  A total of 700 HIV-1 infected participants, randomized in a 1:1 ratio to 2 groups would achieve at least 95% power to establish noninferiority in Week 48 response (HIV-1 RNA < 50 copies/mL per the FDA-defined snapshot analysis) rate difference between the 2 groups. For sample size and power computation, it was assumed that both treatment groups have a response rate of 0.795, a noninferiority margin of 0.12, and that the significance level of the test is at a one-sided, 0.025 level.
[3] Other relevant estimation information:
  To preserve the overall alpha level: 0.05, accounting for 2 interim analyses for Independent Data Monitoring Committee meetings, the 95.2% CI was computed using normal approximation stratified by baseline HIV-1 RNA (≤ 100,000 or > 100,000 copies/mL).



2.  Secondary:   The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96   [ Time Frame: Week 96 ]

3.  Secondary:   The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144   [ Time Frame: Week 144 ]

4.  Secondary:   The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Week 48 ]

5.  Secondary:   The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, and 144   [ Time Frame: Baseline; Weeks 48, 96, and 144 ]

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


  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.


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