Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects
Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Emtricitabine (FTC) (Drug); Tenofovir Disoproxil Fumarate (TDF) (Drug); Efavirenz (EFV) (Drug); FTC/TDF (Drug); FTC/TDF/EFV (Drug); Lamivudine/zidovudine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Gilead Sciences Official(s) and/or principal investigator(s): Andrew Cheng, MD, PhD, Study Director, Affiliation: Gilead Sciences
Summary
The purpose of Study GS-01-934 was to assess the efficacy and safety of two simplified
antiretroviral treatment (ART) regimens in ART-naive, human immunodeficiency virus, type 1
(HIV-1) infected participants. The primary objective of the study was to assess
noninferiority of emtricitabine (FTC) and tenofovir disoproxil fumarate (tenofovir DF; TDF)
in combination with efavirenz (EFV) relative to Combivir (CBV) in combination with EFV in
the treatment of HIV-1 infected ART-naive participants, determined by the achievement and
maintenance of confirmed HIV-1 ribonucleic acid (RNA) < 400 copies/mL (c/mL) through Week
48, as defined by the United States (US) Food and Drug Administration (FDA)
time-to-loss-of-virologic-response (TLOVR) algorithm.
Clinical Details
Official title: A Phase 3, Randomized, Multicenter Study of the Treatment of Antiretroviral-Naive HIV-1 Infected Subjects Comparing Tenofovir Disoproxil Fumarate and Emtricitabine in Combination With Efavirenz vs Combivir (Lamivudine/Zidovudine) and Efavirenz
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time-to-Loss-of Virologic Response [TLOVR] Algorithm
Secondary outcome: Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm)Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48. Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48 Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48 Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48 Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48 Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48 Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48 Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48 Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm) Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96 Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96 Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96 Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96 Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96 Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96 Change in Limb Fat (kg) From Week 48 to Week 96 Change in Trunk Fat (kg) From Week 48 to Week 96 Change in Total Body Fat (kg) From Week 48 to Week 96 Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm) Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144 Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144 Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144 Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144 Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144 Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144 Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144 Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144 Change in Limb Fat (kg) From Week 48 to Week 144 Change in Trunk Fat (kg) From Week 48 to Week 144 Change in Total Body Fat (kg) From Week 48 to Week 144 Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96) Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96) Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) From Week 144 (Atripla Baseline) Through Week 240 (Atripla Week 96) Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96) Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96) Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96) Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) Change in Trunk Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) Change in Total Body Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) Treatment Satisfaction Questionnaire (Satisfaction With Convenience and Simplicity of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. Treatment Satisfaction Questionnaire (Satisfaction With Current Treatment Regimen to Control HIV): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. Treatment Satisfaction Questionnaire (Satisfaction With Tolerability of Current Treatment Regimen) Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. Treatment Satisfaction Questionnaire (Bothered With the Side Effects of Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline. Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96) Quality of Life (SF-12v2 Health Survey: Mental Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)
Detailed description:
This study was originally planned as a 48-week, Phase 3, randomized, open-label, multicenter
study comparing EFV+FTC+TDF (administered as the individual component drugs) versus CBV
(lamivudine/zidovudine) + EFV to assess the efficacy and safety of both treatments in
ART-Naive, HIV-1 infected participants. The regimen of CBV (administered twice daily) + EFV
(administered once daily) served as the active control treatment and was compared with the
regimen of EFV+FTC+TDF; each component drug in the EFV+FTC+TDF regimen was administered once
daily.
Week 48 to Week 96:
The study was extended and continued to evaluate the efficacy and safety of the two regimens
up to a total treatment duration of 96 weeks. The regimen of EFV+FTC+TDF continued to be
dosed as the component drugs (EFV + FTC + TDF), once daily, without regard to meals. The
regimen of CBV+EFV was dosed as 2 pills (CBV, twice daily in the morning without regard to
meals) + EFV (once daily, without regard to meals).
Week 96 to Week 144:
A further study extension changed the 3-pill EFV+FTC+TDF regimen to a 2-pill regimen of EFV
+ Truvada ([TVD]: a fixed-dose combination pill containing FTC/TDF), once daily without
regard to meals, and continued to evaluate the efficacy and safety of the two regimens for a
further 48 weeks up to a total study treatment duration of 144 weeks. The regimen of CBV+EFV
continued to be dosed as 2 pills (CBV, twice daily in the morning without regard to meals) +
EFV (once daily, without regard to meals).
Week 144 to end of study (Week 240):
A final study extension provided all study participants from both treatment regimens the
option to switch their respective treatments to the 1-pill regimen of for a further 96 weeks
up to a total study duration of 240 weeks (5 years) to further assess the efficacy and
safety of ART regimen simplification. At sites in France, the study was extended by a
further 48 weeks (Year 6) or until ATR became commercially available (whichever happened
first); once ATR became commercially available in France participants were not required to
complete the full 288 weeks of the study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria: Participants must have met all inclusion criteria within 28 days prior
to randomization unless specified otherwise including:
- Plasma HIV-1 RNA levels greater than 10,000 c/mL using Roche Amplicor HIV-1 Monitor
Test Version 1. 5 Standard
- Adequate renal function: Calculated creatinine clearance greater than or equal to 50
mL/min according to the Cockcroft-Gault Formula.
- Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase
[ALT]) 3 x upper limit of normal (ULN).
- Total bilirubin less than or equal to 1. 5 mg/dL.
- Adequate hematologic function (absolute neutrophil count greater than or equal to
1,000/mm^3; platelets greater than or equal to 50,000/mm^3; hemoglobin greater than
or equal to 8. 0 g/dL).
- Serum amylase less than or equal to 1. 5 x ULN.
- Serum phosphorus greater than or equal to 2. 2 mg/dL.
- Willingness to use effective contraception by both males and females while on study
treatment and for 30 days following study drug completion.
- Life expectancy greater than or equal to 1 year
- The ability to understand and sign written informed consent form obtained prior to
initiation of study procedures.
Exclusion Criteria: Participants were not eligible for entry to the study if any of the
following were met:
- Prior treatment with any non-nucleoside reverse transcriptase inhibitor (NNRTI),
nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI).
- A new AIDS-defining condition diagnosed (exception CD4 criteria) within 30 days of
baseline.
- Receiving ongoing therapy with any of the following: nephrotoxic agents, probenecid,
systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2, drugs that
interact with efavirenz. Administration of any of the above medications must be
discontinued at least 30 days prior to baseline visit and for duration of study.
- Pregnant or lactating participants.
- Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma.
Participants with biopsy-confirmed KS were eligible but must not have received any
systemic therapy for KS within 30 days of baseline and not anticipated starting
systemic therapy during the study.
- Prior history of renal or bone disease.
- Any other clinical condition prior to therapy that would make the participant
unsuitable for the study or unable to comply with the dosing requirements in the
opinion of the investigator.
Locations and Contacts
AIDS Healthcare Foundation Research, Beverly Hills, California 90211, United States
Capital Medical Associates, P.C., Washington, District of Columbia 20036, United States
Orlando Immunology Center, Orlando, Florida 32804, United States
NorthStar Medical Center, Chicago, Illinois 60657, United States
Jemsek Clinic, Huntersville, North Carolina 28078, United States
Additional Information
Gilead Website Viread website Emtriva website Sustiva website
Starting date: July 2003
Last updated: October 11, 2010
|