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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 28, 2014
Last verified: February 2014
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 for the Week 48 analysis was on 18 September 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
901 participants were screened and 799 were randomized; 786 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)
EFV/FTC/TDF Participants were randomized to receive efavirenz (EFV)/FTC/TDF

Participant Flow:   Overall Study
    FTC/RPV/TDF     EFV/FTC/TDF  
STARTED     400     399  
Randomized and Treated     394     392  
Discontinued Prior to Week 48     37     50  
COMPLETED     0     0  
NOT COMPLETED     400     399  
Randomized but not treated                 6                 7  
Adverse Event                 4                 12  
Death                 0                 1  
Lack of Efficacy                 5                 1  
Physician Decision                 2                 3  
Withdrawal by Subject                 5                 16  
Lost to Follow-up                 15                 13  
Subject Non-Compliance                 5                 4  
Protocol Violation                 1                 0  
Subject Still on Study at Week 48                 357                 342  



  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 Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF
Total Total of all reporting groups

Baseline Measures
    FTC/RPV/TDF     EFV/FTC/TDF     Total  
Number of Participants  
[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     22     31     53  
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  
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-modifying agent  
[units: participants]
     
Yes     52     54     106  
No     342     338     680  
[1] All randomized participants were analyzed for Region of Enrollment



  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 ]

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.
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 medication

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of 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 conventional 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:   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 No text entered.
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.
Participants in the Full Analysis Set with available data were analyzed; the missing = excluded method was used in which all participants with missing data were excluded from analysis.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  357     346  
Change From Baseline in CD4 Cell Count at Week 48  
[units: cells/μL]
Mean ± Standard Deviation
  200  ± 158.6     191  ± 144.3  


Statistical Analysis 1 for Change From Baseline in CD4 Cell Count at Week 48
Groups [1] All groups
Method [2] ANOVA
P Value [3] 0.34
Difference in LSM [4] 11
95% Confidence Interval ( -11 to 32 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value, and difference in least square means (LSM) and its 95% CI are from analysis of variance (ANOVA) with treatment and baseline HIV-1 RNA levels (≤ 100,000, > 100,000 copies/mL) as fixed effect.
[4] Other relevant estimation information:
  No text entered.



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

Measure Type Secondary
Measure Title Change From Baseline in Fasting Total Cholesterol at Week 48
Measure Description No text entered.
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.
Participants in the Full Analysis Set with available data were analyzed using the missing = excluded method.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  322     305  
Change From Baseline in Fasting Total Cholesterol at Week 48  
[units: mg/dL]
Mean ± Standard Deviation
  1  ± 28.1     22  ± 31.3  


Statistical Analysis 1 for Change From Baseline in Fasting Total Cholesterol at Week 48
Groups [1] All groups
Method [2] ANOVA
P Value [3] < 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for the difference in change from baseline at Week 48 is from ANOVA with treatment as fixed effect.



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

Measure Type Secondary
Measure Title Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48
Measure Description No text entered.
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.
Participants in the Full Analysis Set with available data were analyzed using the missing = excluded method.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  322     305  
Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48  
[units: mg/dL]
Mean ± Standard Deviation
  2  ± 8.7     8  ± 10.3  


Statistical Analysis 1 for Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48
Groups [1] All groups
Method [2] ANOVA
P Value [3] < 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for the difference in change from baseline at Week 48 is from ANOVA with treatment as fixed effect.



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

Measure Type Secondary
Measure Title Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48
Measure Description No text entered.
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.
Participants in the Full Analysis Set with available data were analyzed using the missing = excluded method.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  322     303  
Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48  
[units: mg/dL]
Mean ± Standard Deviation
  1  ± 24.4     14  ± 28.2  


Statistical Analysis 1 for Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48
Groups [1] All groups
Method [2] ANOVA
P Value [3] < 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for the difference in change from baseline at Week 48 is from ANOVA with treatment as fixed effect.



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

Measure Type Secondary
Measure Title Change From Baseline in Fasting Triglycerides at Week 48
Measure Description No text entered.
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.
Participants in the Full Analysis Set with available data were analyzed using the missing = excluded method.

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  322     305  
Change From Baseline in Fasting Triglycerides at Week 48  
[units: mg/dL]
Mean ± Standard Deviation
  -8  ± 68.9     8  ± 103.0  


Statistical Analysis 1 for Change From Baseline in Fasting Triglycerides at Week 48
Groups [1] All groups
Method [2] ANOVA
P Value [3] < 0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for the difference in change from baseline at Week 48 is from ANOVA with treatment as fixed effect.



7.  Secondary:   Development of HIV-1 Genotypic Resistance Through Week 48, All Participants   [ Time Frame: Baseline to Week 48 ]

Measure Type Secondary
Measure Title Development of HIV-1 Genotypic Resistance Through Week 48, All Participants
Measure Description Participants who experienced either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed for resistance. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48 or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.
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.
Full Analysis Set

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  394     392  
Development of HIV-1 Genotypic Resistance Through Week 48, All Participants  
[units: percentage of participants]
  4.3     0.8  

No statistical analysis provided for Development of HIV-1 Genotypic Resistance Through Week 48, All Participants



8.  Secondary:   Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance   [ Time Frame: Baseline to Week 48 ]

Measure Type Secondary
Measure Title Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance
Measure Description Resistance Analysis Set: participants with either suboptimal virologic response or virologic rebound were considered to have virologic failure and were analyzed. Suboptimal virologic response was assessed at Week 8 and was defined as having HIV-1 RNA ≥ 50 copies/mL and < 1-log10 reduction from baseline at the Week 8 visit, which was confirmed at the subsequent visit. Virologic rebound was defined as having 2 consecutive visits with HIV-1 RNA ≥ 400 copies/mL after achieving HIV-1 RNA < 50 copies/mL, or as having 2 consecutive visits with > 1 log10 increase in HIV-1 RNA from their nadir. In addition, subjects who were on study drugs, had not been analyzed previously, and who had HIV-1 RNA ≥ 400 copies/mL at Week 48, Week 96, or their last visit (at or after Week 8) were also analyzed for resistance at their last visit. Subsequent to the first resistance testing, subjects experiencing repeated confirmed virologic failure were assessed for resistance retesting on a case-by-case basis.
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.
Resistance Analysis Set

Reporting Groups
  Description
FTC/RPV/TDF Participants were randomized to receive FTC/RPV/TDF
EFV/FTC/TDF Participants were randomized to receive EFV/FTC/TDF

Measured Values
    FTC/RPV/TDF     EFV/FTC/TDF  
Number of Participants Analyzed  
[units: participants]
  20     7  
Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance  
[units: participants]
  17     3  

No statistical analysis provided for Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information