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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 517
- 试验地点
- 5
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
EFV+CBV
Participants in this group received EFV 600 mg once daily + Combivir ([CBV]; the fixed dose combination pill containing lamivudine 150 mg + zidovudine 300 mg) taken twice daily from the start of the study until Week 144. At Week 144 all participants who opted to roll over into the additional 96-week study extension received Atripla ([ATR]; the fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg) taken once daily until the end of the study (Week 240). 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.
干预措施: Efavirenz (EFV) (Drug)
EFV+CBV
Participants in this group received EFV 600 mg once daily + Combivir ([CBV]; the fixed dose combination pill containing lamivudine 150 mg + zidovudine 300 mg) taken twice daily from the start of the study until Week 144. At Week 144 all participants who opted to roll over into the additional 96-week study extension received Atripla ([ATR]; the fixed-dose combination tablet containing FTC 200 mg/TDF 300 mg/EFV 600 mg) taken once daily until the end of the study (Week 240). 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.
干预措施: Lamivudine/zidovudine (Drug)
EFV+FTC+TDF
Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. 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.
干预措施: Emtricitabine (FTC) (Drug)
EFV+FTC+TDF
Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. 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.
干预措施: Tenofovir Disoproxil Fumarate (TDF) (Drug)
EFV+FTC+TDF
Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. 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.
干预措施: Efavirenz (EFV) (Drug)
EFV+FTC+TDF
Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. 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.
干预措施: FTC/TDF (Drug)
EFV+FTC+TDF
Participants in this arm received 3 component drugs: efaviren (EFV; 600 mg) + emtricitabine (FTC; 200 mg) + tenofovir disoproxil fumarate (tenofovir DF [TDF]; 300 mg) as 3 separate pills once daily from the start of the study. At 96 weeks Truvada ([TVD] the fixed-dose combination pill containing FTC/TDF [200/300 mg] once daily) replaced the 2 component drugs FTC + TDF; participants continued to receive EFV 600 mg once daily. At Week 144 all participants who opted to roll over into the further 96-week study extension received ATR. 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.
干预措施: FTC/TDF/EFV (Drug)
结局指标
主要结局
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
时间窗: 48 weeks
Participants who achieved/maintained confirmed HIV-1 RNA \< 400 c/mL had to satisfy the following criteria: 1) not experienced death, permanent study drug discontinuation, or addition of new antiretroviral drug except nevirapine in place of EFV prior to Week 48 visit; 2) achieved confirmed HIV-1 RNA \< 400 c/mL on 2 consecutive visits prior to Week 48 visit (ie, the first of the 2 consecutive HIV-1 RNA \< 400 c/mL occurred prior to the Week 48 visit; 3) not had confirmed HIV-1 RNA \> 400 c/mL after achievement of confirmed HIV RNA levels \< 400 c/mL prior to Week 48 visit.
次要结局
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 48 (Defined by FDA TLOVR Algorithm)(Week 48)
- Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 48.(48 weeks)
- Percentage of Participants With HIV-1 RNA < 50 c/mL at Week 48(48 Weeks)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 48(Baseline to 48 weeks)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 48(Baseline to 48 Weeks)
- Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 48(Baseline to 48 Weeks)
- Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 48(Baseline to 48 Weeks)
- Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 48(Study baseline to Week 48)
- Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 48(Study baseline to Week 48)
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)(96 Weeks)
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 96 (Defined by FDA TLOVR Algorithm)(Week 96)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 96(Week 96)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 96(Week 96)
- Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 400 c/mL) at Week 96(Week 96)
- Percentage of Participants With Pure Virologic Failure (HIV-1 RNA < 50 c/mL) at Week 96(Week 96)
- Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 96(Study baseline to Week 96)
- Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 96(Baseline to Week 96)
- Change in Limb Fat (kg) From Week 48 to Week 96(Week 48 to Week 96)
- Change in Trunk Fat (kg) From Week 48 to Week 96(Week 48 to Week 96)
- Change in Total Body Fat (kg) From Week 48 to Week 96(48 weeks to 96 weeks)
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 400 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)(144 weeks)
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 144 (Defined by FDA TLOVR Algorithm)(Week 144)
- Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 144(Week 144)
- Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 144(Week 144)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 400 c/mL) at Week 144(Week 144)
- Percentage of Participants With Loss of Virologic Response (HIV-1 RNA < 50 c/mL) at Week 144(Week 144)
- Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) at Week 144(Week 144)
- Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) at Week 144(Week 144)
- Change From Study Baseline in HIV-1 RNA (Log10 c/mL) at Week 144(Study baseline to Week 144)
- Change From Study Baseline in CD4 Cell Count (Cells/mm^3) at Week 144(Baseline to Week 144)
- Change in Limb Fat (kg) From Week 48 to Week 144(Week 48 to Week 144)
- Change in Trunk Fat (kg) From Week 48 to Week 144(Week 48 to Week 144)
- Change in Total Body Fat (kg) From Week 48 to Week 144(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(Week 144 (Atripla baseline) to Week 240 (Atripla Week 96))
- Percentage of Participants With Confirmed Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96) Defined by the FDA TLOVR Algorithm(Week 144 (Atripla baseline) to Week 240 (Atripla Week 96))
- Percentage of Participants With Plasma HIV-1 RNA < 400 c/mL at Week 240 (Atripla Week 96)(Week 240 (Atripla Week 96))
- Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 240 (Atripla Week 96)(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)(Week 144 (Atripla Baseline) to 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)(Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96))
- Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 400 c/mL) Through Week 240 (Atripla Week 96)(Week 240 (Atripla Week 96))
- Percentage of Participants With Pure Virological Failure (HIV-1 RNA < 50 c/mL) Through Week 240 (Atripla Week 96)(Week 240 (Atripla Week 96))
- Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 240 (Atripla Week 96)(Study/Atripla baseline to Week 240 (Atripla Week 96))
- Change in Limb Fat (kg) From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)(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)(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)(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.(Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96))
- 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.(Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96))
- Treatment Satisfaction Questionnaire (Satisfaction With Tolerability of Current Treatment Regimen) Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.(Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96))
- Treatment Satisfaction Questionnaire (General Satisfaction With Current Treatment Regimen): Change From Week 144 to Week 240 in the Category Shift From Atripla Baseline.(Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96))
- 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.(Week 144 ([W 144]; Atripla baseline) to Week 240 ([W 240]; Atripla Week 96))
- Quality of Life (SF-12v2 Health Survey: Physical Component Summary) Change From Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96)(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)(Week 144 (Atripla Baseline) to Week 240 (Atripla Week 96))