Overview

This trial is active, not recruiting.

Conditions acquired immunodeficiency syndrome, hiv infections
Treatments stribild, cobi, atv, drv, nrti
Phase phase 3
Sponsor Gilead Sciences
Start date May 2011
End date January 2013
Trial size 106 participants
Trial identifier NCT01363011, GS-US-236-0118

Summary

This study is to characterize the effect of cobicistat-based regimens on parameters of renal function in subjects with HIV infection and who have mild to moderate renal impairment, and to assess the safety and tolerability of the regimens in order to generate appropriate dosing recommendations.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with Stribild (EVG/COBI/FTC/TDF) STR for up to 96 weeks.
stribild Stribild®
Stribild® (elvitegravir [EVG] 150 mg/cobicistat [COBI] 150 mg/emtricitabine [FTC] 200 mg/tenofovir disoproxil fumarate [TDF] 300 mg) single-tablet regimen (STR) administered orally once daily.
(Experimental)
Participants who have received prior ARV treatment and who are virologically suppressed at baseline will continue their treatment regimen, switching the regimen's pharmacoenhancer component from ritonavir to COBI, and continuing their existing protease inhibitor (PI; either ATV or DRV)/2 NRTI regimen for up to 96 weeks.
cobi Tybost®
Cobicistat (COBI, /co) 150 mg tablet administered with food orally once daily
atv Reyataz®
Atazanavir (ATV) 300 mg tablet administered orally once daily
drv Prezista®
Darunavir (DRV) 800 mg tablet administered orally once daily
nrti
Participants will receive 2 investigator-selected nucleoside reverse transcriptase inhibitors (NRTIs), which may include abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or FTC/TDF, administered according to prescribing information.

Primary Outcomes

Measure
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
time frame: Baseline; Week 24
Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
time frame: Baseline; Week 24
Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
time frame: Baseline; Week 24
Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
time frame: Baseline; Week 24
Change From Baseline in eGFR Using the Chronic Kidney Disease, Epidemiology Collaboration (CKD-EPI) Formula Based on Cystatin C Equation at Week 24 (Cohort 1)
time frame: Baseline; Week 24
Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
time frame: Baseline; Week 24
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
time frame: Baseline; Week 24
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
time frame: Baseline; Week 24
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
time frame: Baseline; Weeks 2, 4, and 24
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
time frame: Baseline; Weeks 2, 4, and 24
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
time frame: Week 24
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
time frame: Week 24

Secondary Outcomes

Measure
Change From Baseline in eGFR-CG at Week 48 (Cohort 1)
time frame: Baseline; Week 48
Change From Baseline in eGFR-CG at Week 48 (Cohort 2)
time frame: Baseline; Week 48
Change From Baseline in eGFR-MDRD at Week 48 (Cohort 1)
time frame: Baseline; Week 48
Change From Baseline in eGFR-MDRD at Week 48 (Cohort 2)
time frame: Baseline; Week 48
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Week 48 (Cohort 1)
time frame: Baseline; Week 48
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Week 48 (Cohort 2)
time frame: Baseline; Week 48
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 48 (Cohort 1)
time frame: Baseline; Week 48
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 48 (Cohort 2)
time frame: Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (Cohort 1)
time frame: Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (Cohort 2)
time frame: Week 48
Percentage of Participants Who Experienced Adverse Events (Cohort 1)
time frame: Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Adverse Events (Cohort 2)
time frame: Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
time frame: Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
time frame: Up to 48 weeks plus 30 days
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
time frame: Week 2, 4, and 24
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
time frame: Week 2, 4, and 24

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Cohort 1 (treatment-naive) - Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening - Screening genotype report must show sensitivity to FTC and TDF - No prior use of any approved or investigational antiretroviral drug for any length of time Cohort 2 (treatment-experienced, pharmacoenhancer switch) - Subjects must be receiving ATV 300 mg/ritonavir (RTV) 100 mg plus 2 NRTIs OR DRV 800 mg/RTV 100 mg plus 2 NRTIs for at least 6 months prior to screening - Plasma HIV-1 RNA concentrations at undetectable levels in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening - Subjects experiencing intolerance to RTV (as determined by the investigator) Both groups - The ability to understand and sign a written informed consent form - Normal ECG - Mild to moderate renal function - Stable renal function - Hepatic transaminases (AST and ALT) ≤ 5 x the upper limit of the normal range (ULN) - Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert's Syndrome or hyperbilirubinemia due to atazanavir therapy may have total bilirubin up to 5 x ULN) - Adequate hematologic function - Serum amylase ≤ 5 x ULN - 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 drug - Age ≥ 18 years Exclusion Criteria: - New AIDS-defining condition diagnosed within the 30 days prior to screening - Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C - Subjects experiencing decompensated cirrhosis - Females who are breastfeeding - Positive serum pregnancy test (female of childbearing potential) - Implanted defibrillator or pacemaker - Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance - History of malignancy within the past 5 years or ongoing malignancy 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 - Receiving ongoing therapy with any of medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR, COBI tablets, ATV capsules or DRV tablets or contraindicated for the 2 NRTIs as part of the PI/co regimen - Participation in any other clinical trial without prior approval - Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Additional Information

Official title A Phase 3 Open-label Safety Study of Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Gilead Sciences.