A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9350-boosted Atazanavir (ATV/GS-9350) Compared to Ritonavir-boosted Atazanavir (ATV/r) in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 31
- 主要终点
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
研究概览
简要总结
The objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adults.
Participants will be randomized in a 2:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded, at which point all participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive ATV+COBI+FTC/TDF until COBI tablets become commercially available, or until Gilead Sciences elects to terminate the study.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Ability to understand and sign a written informed consent form
- •Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
- •No prior use of any approved or experimental anti-HIV drug
- •Normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
- •Adequate renal function (estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula)
- •Hepatic transaminases ≤ 2.5 × upper limit of normal
- •Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- •Adequate hematologic function (absolute neutrophil count ≥ 1000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
- •Cluster of differentiation 4 (CD4) cell count > 50 cells/µL
- •Serum amylase ≤ 1.5 × ULN (subjects with serum amylase >1.5 × ULN remained eligible if serum lipase is ≤ 1.5 × ULN)
- •Normal thyroid-stimulating hormone
- •Negative serum pregnancy test (females of childbearing potential only)
- •Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs
- •Age ≥ 18 years
- •Life expectancy ≥ 1 year
排除标准
- •New AIDS-defining condition diagnosed within the 30 days prior to screening
- •Documented drug resistance to nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or primary PI resistance mutation(s)
- •Hepatitis B surface antigen positive
- •Hepatitis C antibody positive
- •Participants experiencing cirrhosis
- •Participants experiencing ascites
- •Participants experiencing encephalopathy
- •Females who are breastfeeding
- •Positive serum pregnancy test (female of childbearing potential)
- •Vaccinated within 90 days of study dosing
- •History or family history of Long QT Syndrome or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30 years
- •Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
- •Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) interval at screening (eg, a prolongation of the QTcF interval of greater than 450 msec for males and greater than 470 msec for females)
- •PR interval greater than or equal to 200 msec or less than or equal to 120 msec on ECG at screening
- •QRS greater than or equal to 120 msec on ECG at screening
- •Implanted defibrillator or pacemaker
- •Subjects receiving ongoing therapy with any disallowed medications
- •Current alcohol or substance use judged to potentially interfere with subject study compliance
- •History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- •Participation in any other clinical trial without prior approval
- •Medications contraindicated for use with ATV, RTV, FTC, or TDF
- •Any known allergies to the excipients of ATV capsules, RTV capsules, COBI tablets or FTC/TDF tablets
- •Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements
研究组 & 干预措施
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
干预措施: COBI (Drug)
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
干预措施: ATV (Drug)
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
干预措施: FTC/TDF (Drug)
ATV+COBI+FTC/TDF
COBI + RTV placebo +ATV+FTC/TDF for 48 weeks
干预措施: RTV placebo (Drug)
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
干预措施: RTV (Drug)
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
干预措施: ATV (Drug)
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
干预措施: FTC/TDF (Drug)
ATV+RTV+FTC/TDF
RTV + COBI placebo +ATV+FTC/TDF for 48 weeks
干预措施: COBI placebo (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
时间窗: Week 24
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the missing = failure method, where participants with missing data were considered to have failed to achieve the endpoint.
次要结局
- Change From Baseline in HIV-1 RNA at Week 48(Baseline to Week 48)
- Change From Baseline in CD4 Cell Count at Week 24(Baseline to Week 24)
- Change From Baseline in CD4 Cell Count at Week 48(Baseline to Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48(Week 48)
- Change From Baseline in HIV-1 RNA at Week 24(Baseline to Week 24)