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

• ClinicalTrials.gov Identifier: NCT01309243
• Recruitment Status: Completed
• First Posted: March 7, 2011
• Results First Posted: November 27, 2013
• Last Update Posted: February 25, 2015
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: March 3, 2011
• First Posted Date: March 7, 2011
• Results First Submitted Date: September 25, 2013
• Results First Posted Date: November 27, 2013
• Last Update Posted Date: February 25, 2015
• Study Start Date: February 2011
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2015)

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

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.

• Original Primary Outcome Measures (submitted: March 3, 2011): The primary efficacy endpoint is the proportion of subjects who achieve HIV 1 RNA < 50 copies/mL at week 48 [ Time Frame: 48 Weeks ]

Current Secondary Outcome Measures (submitted: February 3, 2015)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Baseline to Week 96 ]
  The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the US FDA snapshot algorithm.
• Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ]
• Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline to Week 96 ]
• Change From Baseline in Fasting Total Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ]
• Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ]
• Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ]
• Change From Baseline in Fasting Triglycerides at Week 48 [ Time Frame: Baseline to Week 48 ]
• Development of HIV-1 Drug Resistance Through Week 96, All Participants [ Time Frame: Baseline to Week 96 ]
  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, 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.
• Development of HIV-1 Drug Resistance Through Week 96, Participants With Viral Resistance [ Time Frame: Baseline to Week 96 ]
  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.

Original Secondary Outcome Measures (submitted: March 3, 2011)

• The change from baseline in CD4 count in each treatment arm at week 48 [ Time Frame: 48 Weeks ]
• The change from baseline in CD4 count in each treatment arm at week 96 [ Time Frame: 96 Weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase 3B, Randomized, Open-label 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

Brief Summary

The purpose of the study was to evaluate the safety and efficacy of the emtricitabine (FTC)/rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF) single-tablet regimen (STR) compared with the efavirenz (EFV)/FTC/TDF STR in HIV-1 infected adults who had not previously received treatment with antiretroviral medications.

Participants were randomized in a 1:1 ratio to receive one of the study treatments. Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. A treatment duration of 96 weeks was planned, with the option for subjects in FTC/RPV/TDF STR arm to receive treatment following the Week 96 visit until FTC/RPV/TDF STR is commercially available or until Gilead Sciences elects to terminate development in that country.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• Drug: FTC/RPV/TDF
  Emtricitabine (FTC) 200 mg/rilpivirine (RPV) 25 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen administered orally once daily with a meal
  Other Names:

  • Complera®
  • Eviplera®
• Drug: EFV/FTC/TDF
  Efavirenz (EFV) 600 mg/FTC 200 mg/TDF 300 mg single-tablet regimen administered orally once daily on an empty stomach, preferably at bedtime
  Other Name: Atripla®

Study Arms

• Experimental: FTC/RPV/TDF
  Intervention: Drug: FTC/RPV/TDF
• Experimental: EFV/FTC/TDF
  Intervention: Drug: EFV/FTC/TDF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 25, 2013): 799
• Original Estimated Enrollment (submitted: March 3, 2011): 700
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Plasma HIV-1 RNA levels ≥ 2,500 copies/mL at screening
• No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report showing sensitivity to EFV, FTC, TDF, and lack of the RPV mutations K101E/P, E138A/G/K/Q/R, Y181C/I/V, and H221Y
• Normal ECG
• Hepatic transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 5 x the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN (participants with serum amylase > 5 x ULN remained eligible if serum lipase was ≤ 5 x ULN)
• Adequate renal function
• Males and Females of childbearing potential must have agreed to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study period and for 12 weeks following the last dose of study drug.
• Adult (≥ 18 years) males or non-pregnant females

Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Females who were breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Proven or suspected acute hepatitis in the 30 days prior to study entry
• Subjects receiving drug treatment for hepatitis C, or subjects who were anticipated to receive treatment for hepatitis C during the course of the study
• Subjects experiencing decompensated cirrhosis
• Had an implanted defibrillator or pacemaker
• Current alcohol or substance abuse
• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Receiving ongoing therapy or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use, including drugs not to be used with FTC, EFV, RPV, or TDF; or subjects with known allergies to the excipients of the FTC/RPV/TDF or EFV/FTC/TDF single-tablet regimens
• Participation in any other clinical trial without prior approval from the sponsor was prohibited while participating in this trial.
• Had been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids for immunosuppression during the study (eg, corticosteroids, immunoglobulins, and other immune-based or cytokine-based therapies)
• Had any other clinical condition or prior therapy that, in the opinion of the Investigator, would have made the participant unsuitable for the study or unable to comply with the dosing requirements

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Portugal, Puerto Rico, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT01309243
• Other Study ID Numbers: GS-US-264-0110
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Chair: Todd Fralich, M.D.; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2015