A Randomized, Open Label, Phase 4 Study Evaluating the Renal Effect of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF or Other Tenofovir DF-containing Regimens (Ritonavir-boosted Atazanavir Plus Emtricitabine/Tenofovir DF or Efavirenz/Emtricitabine/Tenofovir DF) Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naïve HIV-1 Infected Adults With eGFR ≥70 mL/Min
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 72
- 主要终点
- Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24
研究概览
简要总结
The primary objective of this study is to assess glomerular function before and during administration of stribild (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) or a regimen containing TDF without cobicistat (COBI) as ritonavir (RTV)-boosted atazanavir (ATV/r) plus truvada (TVD; FTC/TDF) or atripla (ATR; efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)) compared to a regimen containing neither TDF nor COBI as ATV/r plus abacavir/lamivudine (ABC/3TC) via determination of actual glomerular filtration rate (aGFR) using iohexol (a probe GFR marker) plasma clearance and estimated (calculated) glomerular filtration rate (eGFR).
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment naïve
- •Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening
- •CD4 cell count > 200 cells/µL
- •Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT
- •Estimated GFR ≥ 70 mL/min
- •Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin
- •Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
- •Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
- •Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG
- •Not pregnant or non-lactating females of non-childbearing potential. Or females with childbearing potential who agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose
- •Males who agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose. Males who agree to refrain from sperm donation from first dose until at least 90 days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug dose
- •Body mass index (BMI) of 19 ≤ BMI ≤ 30 kg/m^2 and body weight ≥ 40 kg
- •Life expectancy ≥ 1 year
排除标准
- •HLA-B*5701 allele positive
- •A new AIDS-defining condition diagnosed within the 30 days prior to screening
- •Hepatitis B surface antigen (HBsAg) positive
- •Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
- •Individuals experiencing decompensated cirrhosis
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Have an implanted defibrillator or pacemaker
- •Current alcohol or substance that could potentially interfere with study compliance
- •A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 Visit and must not be anticipated to require systemic therapy during the study
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
STB+iohexol
Participants will receive STB+iohexol for 24 weeks.
干预措施: STB (Drug)
STB+iohexol
Participants will receive STB+iohexol for 24 weeks.
干预措施: Iohexol (Drug)
RTV+ATV+TVD+iohexol
Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.
干预措施: TVD (Drug)
RTV+ATV+TVD+iohexol
Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.
干预措施: RTV (Drug)
RTV+ATV+TVD+iohexol
Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.
干预措施: ATV (Drug)
RTV+ATV+TVD+iohexol
Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.
干预措施: Iohexol (Drug)
ATR+iohexol
Participants will receive ATR+iohexol for 24 weeks.
干预措施: ATR (Drug)
ATR+iohexol
Participants will receive ATR+iohexol for 24 weeks.
干预措施: Iohexol (Drug)
RTV+ATV+ABC/3TC+iohexol
Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.
干预措施: RTV (Drug)
RTV+ATV+ABC/3TC+iohexol
Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.
干预措施: ATV (Drug)
RTV+ATV+ABC/3TC+iohexol
Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.
干预措施: ABC/3TC (Drug)
RTV+ATV+ABC/3TC+iohexol
Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.
干预措施: Iohexol (Drug)
结局指标
主要结局
Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24
时间窗: Week 24
Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24
时间窗: Week 24
MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender. eGFR (mL/min/1.73 m\^2) = 186 \* (Scr)\^-1.154 \* (Age)\^(-0.203) \* (0.742 if female) \* (1.212 if black). Scr = serum creatinine in mg/dL
Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24
时间窗: Week 24
GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFR = (140 - age) \* (mass in kg) \* (0.85 if female) divided by 72 \* serum creatinine in mg/dL
次要结局
- PK Parameter: Clast for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)(Up to 24 weeks plus 30 days)
- Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)(Up to 24 weeks plus 30 days)
- Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24(Baseline; Week 24)
- Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24(Baseline; Week 24)
- Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24(Baseline; Week 24)
- Pharmacokinetic (PK) Parameter: Cmax for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tmax for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Clast for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tlast for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Ctau for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: λz for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: AUCtau for COBI(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: t1/2 for COBI(Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Cmax for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tmax for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24(Baseline; Week 24)
- PK Parameter: λz for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: t1/2 for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tmax for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tlast for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Ctau for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: AUCtau for RTV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Cmax for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Clast for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Tlast for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: Ctau for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: λz for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: AUCtau for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: t1/2 for TFV(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24)
- PK Parameter: AUCinf for Iohexol(Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" on Day 1 and Weeks 4, 8, 16, and 24)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm(Week 24)
- Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24(Baseline; Week 24)
- Percentage of Participants Experiencing Adverse Events (AEs)(Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days))
- Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities(Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days))