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
  Purpose

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. The FTC/RPV/TDF STR offers an alternative treatment option to patients who wish to simplify or improve the tolerability of their treatment regimen.

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.


Condition Intervention Phase
HIV-1 Infection
Drug: FTC/RPV/TDF
Drug: EFV/FTC/TDF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the US FDA snapshot algorithm.


Secondary Outcome Measures:
  • Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Total Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting High-density Lipoprotein (HDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Fasting Triglycerides at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Development of HIV-1 Genotypic Resistance Through Week 48, All Participants [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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.

  • Development of HIV-1 Genotypic Resistance Through Week 48, Participants With Viral Resistance [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    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.


Enrollment: 799
Study Start Date: February 2011
Study Completion Date: February 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTC/RPV/TDF 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®
Experimental: EFV/FTC/TDF 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®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, E138G/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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309243

  Show 151 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: Todd Fralich, M.D. Gilead Sciences
  More Information

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 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
HIV-1
Antiretroviral Treatment-Naïve

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Tenofovir disoproxil
Efavirenz
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 29, 2014