Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

Gilead Sciences106 enrolled

Overview

This study is to characterize the effect of cobicistat-based regimens on parameters of renal function in participants 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

106

Conditions

Acquired Immunodeficiency Syndrome HIV Infections

Interventions

E/C/F/TDFDRUG

E/C/F/TDF (150/150/200/300 mg) STR administered orally once daily

COBIDRUG

COBI 150 mg tablet administered with food orally once daily

ATVDRUG

ATV 300 mg tablet administered orally once daily

DRV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 elvitegravir (EVG), COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of E/C/F/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

Locations (51)

Outcomes

Primary Outcomes

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)

Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).

Time frame: Baseline; Week 24

Change From Baseline in eGFR-CG at Week 24 (Cohort 2)

Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).

Time frame: Baseline; Week 24

Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)

Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area.

Time frame: Baseline; Week 24

Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)

Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area.

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)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area.

Time frame: Baseline; Week 24

Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area.

Data from ClinicalTrials.gov

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Secondary Outcomes

Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)

Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)

Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Week 48

Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)

Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)

Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)

Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

Time frame: Baseline; Weeks 48 and 96

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.

Time frame: Weeks 48 and 96

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.

Time frame: Weeks 48 and 96

Percentage of Participants Who Experienced Adverse Events (Cohort 1)

Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 1 (treatment-naive). A participant was counted once if they had a qualifying event.

Time frame: Up to 147 weeks plus 30 days

Percentage of Participants Who Experienced Adverse Events (Cohort 2)

Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 2 (treatment-experienced). A participant was counted once if they had a qualifying event.

Time frame: Up to 166 weeks plus 30 days

Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)

Laboratory abnormalities were summarized for Cohort 1 (treatment-naive) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.

Time frame: Up to 147 weeks plus 30 days

Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)

Laboratory abnormalities were summarized for Cohort 2 (treatment-experienced) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.

Time frame: Up to 166 weeks plus 30 days

Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)

AUCtau was analyzed for Cohort 1 (treatment-naive) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).