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  
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     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  
HIV-1 RNA  
[units: log10┬ácopies/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  
[1] All randomized participants were analyzed for Region of Enrollment



  Outcome Measures
  Show All Outcome Measures

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

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
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Time Frame Baseline through Week 96 (Randomized Phase), and Week 96 up to a maximum of 954 days (Extension Phase)
Additional Description Safety Analysis Set

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

Serious Adverse Events
    FTC/RPV/TDF     EFV/FTC/TDF  
Total, serious adverse events      
# participants affected / at risk     36/394 (9.14%)     48/392 (12.24%)  
Blood and lymphatic system disorders      
Haemolytic anaemia † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Cardiac disorders      
Myocardial infarction † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Tachycardia † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Ear and labyrinth disorders      
Hypoacusis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Gastrointestinal disorders      
Rectal haemorrhage † 1    
# participants affected / at risk     0/394 (0.00%)     2/392 (0.51%)  
Abdominal pain † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Anal fistula † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Colitis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Gastritis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Inguinal hernia † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Large intestine perforation † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Vomiting † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     2/394 (0.51%)     0/392 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     0/394 (0.00%)     2/392 (0.51%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Hepatobiliary disorders      
Cholecystitis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Cholelithiasis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Liver injury † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Immune system disorders      
Anaphylactic reaction † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Hypersensitivity † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Infections and infestations      
Appendicitis † 1    
# participants affected / at risk     2/394 (0.51%)     0/392 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Gastroenteritis † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Neurosyphilis † 1    
# participants affected / at risk     0/394 (0.00%)     2/392 (0.51%)  
Ophthalmic herpes zoster † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Abscess limb † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Anal abscess † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Arthritis bacterial † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Atypical pneumonia † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Bronchitis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Eye infection syphilitic † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Furuncle † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Gastroenteritis shigella † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Meningitis aseptic † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Meningitis viral † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Rectal abscess † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Secondary syphilis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Sepsis † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Septic shock † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Staphylococcal bacteraemia † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Staphylococcal infection † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Injury, poisoning and procedural complications      
Concussion † 1    
# participants affected / at risk     2/394 (0.51%)     0/392 (0.00%)  
Ankle fracture † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Clavicle fracture † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Fall † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Femoral neck fracture † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Limb injury † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Patella fracture † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Radius fracture † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Tendon rupture † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Upper limb fracture † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Wrist fracture † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Investigations      
Hepatic enzyme increased † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Musculoskeletal and connective tissue disorders      
Arthritis reactive † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Back pain † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Tenosynovitis † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Burkitt’s lymphoma † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Anal squamous cell carcinoma † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Anogenital warts † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Craniopharyngioma † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Gliosarcoma † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Prostate cancer † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Rectal cancer stage 0 † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Testicular germ cell cancer † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Thyroid cancer † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Nervous system disorders      
Convulsion † 1    
# participants affected / at risk     0/394 (0.00%)     2/392 (0.51%)  
Syncope † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Transient ischaemic attack † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Cerebrovascular accident † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Headache † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Partial seizures † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Pregnancy, puerperium and perinatal conditions      
Abortion spontaneous † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Psychiatric disorders      
Depression † 1    
# participants affected / at risk     2/394 (0.51%)     2/392 (0.51%)  
Suicide attempt † 1    
# participants affected / at risk     1/394 (0.25%)     3/392 (0.77%)  
Major depression † 1    
# participants affected / at risk     2/394 (0.51%)     1/392 (0.26%)  
Suicidal ideation † 1    
# participants affected / at risk     2/394 (0.51%)     1/392 (0.26%)  
Bipolar I disorder † 1    
# participants affected / at risk     1/394 (0.25%)     1/392 (0.26%)  
Alcohol abuse † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Completed suicide † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Delirium tremens † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Mental status changes † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Renal and urinary disorders      
Nephrolithiasis † 1    
# participants affected / at risk     2/394 (0.51%)     1/392 (0.26%)  
Reproductive system and breast disorders      
Cervical dysplasia † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Epididymitis † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Respiratory, thoracic and mediastinal disorders      
Asphyxia † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Epistaxis † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Pulmonary embolism † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Skin and subcutaneous tissue disorders      
Leukocytoclastic vasculitis † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Vascular disorders      
Accelerated hypertension † 1    
# participants affected / at risk     0/394 (0.00%)     1/392 (0.26%)  
Behcet’s syndrome † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Deep vein thrombosis † 1    
# participants affected / at risk     1/394 (0.25%)     0/392 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA Version 16.1




  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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  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: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


No publications provided


Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01309243     History of Changes
Other Study ID Numbers: GS-US-264-0110
Study First Received: March 3, 2011
Results First Received: September 25, 2013
Last Updated: February 3, 2015
Health Authority: United States: Food and Drug Administration