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Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Compared With a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01309243
First received: March 3, 2011
Last updated: February 3, 2015
Last verified: February 2015
Results First Received: September 25, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Drug: FTC/RPV/TDF
Drug: EFV/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
Subjects were enrolled in a total of 121 study sites in North America, Europe, and Australia. The first participant was screened on 23 February 2011. The last participant observation was on 03 February 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
991 participants were screened.

Reporting Groups
  Description
FTC/RPV/TDF Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen (STR) administered orally once daily
EFV/FTC/TDF Efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg STR administered orally once daily

Participant Flow for 2 periods

Period 1:   Randomized Phase Through Week 96
    FTC/RPV/TDF   EFV/FTC/TDF
STARTED   400   399 
Randomized and Treated   394   392 
COMPLETED   316   290 
NOT COMPLETED   84   109 
Randomized but not treated                6                7 
Adverse Event                12                43 
Death                0                1 
Pregnancy                2                0 
Lack of Efficacy                16                4 
Investigators Discretion                3                6 
Withdrew Consent                12                18 
Lost to Follow-up                23                22 
Subject Non-Compliance                9                7 
Protocol Violation                1                1 

Period 2:   Extension Phase
    FTC/RPV/TDF   EFV/FTC/TDF
STARTED   40 [1]   117 [2] 
COMPLETED   34   117 
NOT COMPLETED   6   0 
Lost to Follow-up                6                0 
[1] 40 participants from the Randomized Phase continued the study in the Extension Phase.
[2] 117 participants from the Randomized Phase continued the study in the Extension Phase.



  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.
Participants in the Safety Analysis Set (randomized and received at least 1 dose of study drug) were analyzed for baseline characteristics.

Reporting Groups
  Description
FTC/RPV/TDF FTC 200 mg/RPV 25 mg/TDF 300 mg STR administered orally once daily
EFV/FTC/TDF EFV 600 mg/FTC 200 mg/TDF 300 mg STR administered orally once daily
Total Total of all reporting groups

Baseline Measures
   FTC/RPV/TDF   EFV/FTC/TDF   Total 
Overall Participants Analyzed 
[Units: Participants]
 394   392   786 
Age 
[Units: Years]
Mean (Standard Deviation)
 37  (10.4)   37  (11.0)   37  (10.7) 
Gender 
[Units: Participants]
     
Female   28   28   56 
Male   366   364   730 
Race/Ethnicity, Customized 
[Units: Participants]
     
American Indian or Alaska Native   3   1   4 
Asian   8   13   21 
Black or African Heritage   98   94   192 
Native Hawaiian or Pacific Islander   4   3   7 
White   266   262   528 
Other   13   19   32 
Not Permitted   1   0   1 
Not Reported   1   0   1 
Race/Ethnicity, Customized 
[Units: Participants]
     
Hispanic/Latino   59   75   134 
Non-Hispanic/Latino   331   315   646 
Not Permitted   3   2   5 
Not Reported   1   0   1 
Region of Enrollment [1] 
[Units: Participants]
     
United States   262   279   541 
Australia   15   25   40 
Canada   28   20   48 
Germany   25   22   47 
France   16   7   23 
United Kingdom   12   8   20 
Puerto Rico   8   10   18 
Spain   9   6   15 
Italy   10   3   13 
Belgium   4   5   9 
Portugal   2   5   7 
Switzerland   2   3   5 
Austria   7   6   13 
[1] All randomized participants were analyzed for Region of Enrollment
HIV-1 RNA 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.8  (0.65)   4.8  (0.61)   4.8  (0.63) 
HIV-1 RNA Category 
[Units: Participants]
     
≤ 100,000 copies/mL   260   250   510 
> 100,000 copies/mL   134   142   276 
Cluster of differentiation 4 (CD4) Cell Count 
[Units: cells/μL]
Mean (Standard Deviation)
 395.7  (179.64)   385.2  (186.82)   390.5  (183.21) 
Use of lipid-lowering agent 
[Units: Participants]
     
Yes   4   1   5 
No   390   391   781 


  Outcome Measures
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1.  Primary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]
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Measure Type Primary
Measure Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Measure Description

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the US FDA snapshot algorithm.

The snapshot algorithm defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.

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.
Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug

Reporting Groups
  Description
FTC/RPV/TDF FTC 200 mg/RPV 25 mg/TDF 300 mg STR administered orally once daily
EFV/FTC/TDF EFV 600 mg/FTC 200 mg/TDF 300 mg STR administered orally once daily

Measured Values
   FTC/RPV/TDF   EFV/FTC/TDF 
Participants Analyzed 
[Units: Participants]
 394   392 
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 
[Units: Percentage of participants]
 85.8   81.6 


Statistical Analysis 1 for Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Difference in the response rates [3] 4.1
95% Confidence Interval -1.1 to 9.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

The analysis was to assess the noninferiority of FTC/RPV/TDF versus EFV/FTC/TDF using a 95% confidence interval (CI) approach, with a noninferiority margin of 12% (lower bound of CI > -12%).

700 subjects allocated 1:1 to either treatment arm was predicted to give > 95% power when the proportion of responders in both treatment groups for the primary endpoint is 80% at Week 48.

[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
 

Null hypothesis: The FTC/RPV/TDF group was at least 12% worse than the EFV/FTC/TDF group with respect to the percentage of subjects achieving HIV-1 RNA < 50 copies/mL (“response rate,” as defined by the snapshot analysis algorithm) at Week 48.

Alternative hypothesis: The FTC/RPV/TDF group was less than 12% worse than the EFV/FTC/TDF group with respect to the percentage of subjects achieving HIV-1 RNA < 50 copies/mL at Week 48.

[3] Other relevant estimation information:
  The baseline stratum-weighted (HIV-1 RNA ≤ 100,000 and > 100,000 copies/mL) difference in virologic success rates and its 95% CI were from baseline HIV-1 RNA adjusted Mantel-Haenszel proportions.



2.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96   [ Time Frame: Baseline to Week 96 ]

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

4.  Secondary:   Change From Baseline in CD4 Cell Count at Week 96   [ Time Frame: Baseline to Week 96 ]

5.  Secondary:   Change From Baseline in Fasting Total Cholesterol at Week 48   [ Time Frame: Baseline to Week 48 ]

6.  Secondary:   Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48   [ Time Frame: Baseline to Week 48 ]

7.  Secondary:   Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48   [ Time Frame: Baseline to Week 48 ]

8.  Secondary:   Change From Baseline in Fasting Triglycerides at Week 48   [ Time Frame: Baseline to Week 48 ]

9.  Secondary:   Development of HIV-1 Drug Resistance Through Week 96, All Participants   [ Time Frame: Baseline to Week 96 ]

10.  Secondary:   Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance   [ Time Frame: Baseline to Week 96 ]


  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
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