Clinical trial NCT02246998: Renal Effect of Stribild or Other Tenofovir DF-containing Regimens Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naive HIV-1 Infected Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-09-23
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: Actual Glomerular Filtration Rate (aGFR) Using Iohexol Plasma Clearance (CLiohexol) at Week 24
timeFrame: Week 24
measure: Estimated GFR (eGFR) Calculated by Cockcroft-Gault Formula at Week 24
timeFrame: Week 24
measure: Estimated GFR Calculated by Modification of Diet in Renal Disease (MDRD) Formula at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Urine Glucose (by Dipstick)
timeFrame: Up to 24 weeks plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormality: Serum Glucose (Fasting)
timeFrame: Up to 24 weeks plus 30 days
measure: Percentage Change From Baseline in Urine Albumin to Creatinine Ratio (mg/g) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage Change From Baseline in Urine Protein to Creatinine Ratio (mg/g) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage Change From Baseline in Urine β2-microglobulin to Creatinine Ratio (µg/g) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Week 24
timeFrame: Baseline; Week 24
measure: Pharmacokinetic (PK) Parameter: Cmax for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tmax for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Clast for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tlast for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Ctau for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: λz for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: AUCtau for COBI
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: t1/2 for COBI
timeFrame: Predose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Cmax for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tmax for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Clast for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tlast for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Ctau for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: AUCtau for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: λz for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: t1/2 for RTV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Cmax for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tmax for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Clast for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Tlast for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: Ctau for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: λz for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: AUCtau for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: t1/2 for TFV
timeFrame: Pre-dose, 0, 0.5, 1, 2, 3, 4, 5, 6, and 10 hours post "time zero" at Weeks 4, 8, 16, and 24
measure: PK Parameter: AUCinf for Iohexol
timeFrame: 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
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL Week 24 as Determined by Snapshot Algorithm
timeFrame: Week 24
measure: Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 24
timeFrame: Baseline; Week 24
measure: Percentage of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)
measure: Percentage of Participants Experiencing Treatment Emergent (TE) Grade 3 or 4 Laboratory Abnormalities
timeFrame: Up to the last dose date plus 30 days (Up to 24 weeks plus 30 days)
Other outcomes:
Locations:
city: Brussels
country: Belgium
city: Ghent
country: Belgium
city: Lyon
country: France
city: Paris
country: France
city: Rennes
country: France
city: Tourcoing
country: France
city: Dublin
country: Ireland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Seville
country: Spain
city: Birmingham
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Brighton
country: United Kingdom
city: Bristol
country: United Kingdom
city: Coventry
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: