Back to resultsCobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
Primary Purpose
Acquired Immunodeficiency Syndrome, HIV Infections
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
E/C/F/TDF
COBI
ATV
DRV
NRTI
Sponsored by
About this trial
This is an interventional treatment trial for Acquired Immunodeficiency Syndrome focused on measuring HIV-1, Treatment Naive, Treatment Experienced
Eligibility Criteria
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
Sites / Locations
- Spectrum Medical Group
- Health for Life Clinic
- AHF Research Center
- Kaiser Permanente
- Peter J. Ruane, M.D., Inc.
- Anthony Mills, MD, Inc.
- Orange Coast Medical Group
- East Bay AIDS Center
- University of California, Davis
- Metropolis Medical
- National Jewish Health
- Yale University School of Medicine AIDS Program
- Whitman Walker Clinic
- Medical Faculty Associates
- Therafirst Medical Center
- Broward Health
- Gary J. Richmond.M.D.,P.A.
- Midway Immunology and Research Center
- Orlando Immunology Center
- IDOCF/ValueHealthMD, LLC
- Infectious Disease Specialists of Atlanta
- Mercer University/ Mercer Medicine Clinical Research
- Northstar Medical Center
- The Research Institute
- Central West Clinical Research, Inc.
- ID Care
- North Shore University Hospital
- Chelsea Village Medical
- Mount Sinai Downtown Comprehensive Health Program
- AIDS Care
- Carolinas Medical Center
- Southwest Infectious Disease Clinical Research, Inc.
- Tarrant County Infectious Disease Associates
- Therapeutic Concepts, PA
- Taylor Square Private Clinic
- Infectious Diseases Unit - The Alfred Hospital
- Holdsworth House Medical Practice
- Landeskrankenhaus Graz West
- Otto Wagner Spital
- Sunnybrook Health Sciences Center
- Clinique Medicale du Quartier Latin
- Instituto Dominicano de Estudio Virologicos
- Center for HIV and Hepatogastroenterology
- Hospital Civil de Guadalajara "Fray Antonio Alcalde"
- Clinical Research Puerto Rico
- HOPE Clinical Research
- Brighton and Sussex University Hospitals NHS Trust
- Barts & the London NHS Trust
- Homerton University Hospital
- Guy's King's and St. Thomas' School of Medicine
- St Stephen's AIDS Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
E/C/F/TDF (Cohort 1)
COBI+PI+2 NRTI (Cohort 2)
Arm Description
Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) single-tablet regimen (STR) for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
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 cobicistat (COBI), and continuing their existing protease inhibitor (PI; either atazanavir (ATV) or darunavir (DRV)) plus 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Outcomes
Primary Outcome Measures
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).
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).
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.
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.
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.
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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (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.
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
AUCtau was analyzed for Cohort 2 (treatment-experienced) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.
Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.
Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.
Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.
Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.
Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01363011
Brief Title
Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immunodeficiency Syndrome, HIV Infections
Keywords
HIV-1, Treatment Naive, Treatment Experienced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
106 (Actual)
8. Arms, Groups, and Interventions
Arm Title
E/C/F/TDF (Cohort 1)
Arm Type
Experimental
Arm Description
Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) single-tablet regimen (STR) for up to 96 weeks.
Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Arm Title
COBI+PI+2 NRTI (Cohort 2)
Arm Type
Experimental
Arm Description
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 cobicistat (COBI), and continuing their existing protease inhibitor (PI; either atazanavir (ATV) or darunavir (DRV)) plus 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen for up to 96 weeks.
Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Intervention Type
Drug
Intervention Name(s)
E/C/F/TDF
Other Intervention Name(s)
Stribild®
Intervention Description
E/C/F/TDF (150/150/200/300 mg) STR administered orally once daily
Intervention Type
Drug
Intervention Name(s)
COBI
Other Intervention Name(s)
Tybost®
Intervention Description
COBI 150 mg tablet administered with food orally once daily
Intervention Type
Drug
Intervention Name(s)
ATV
Other Intervention Name(s)
Reyataz®
Intervention Description
ATV 300 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
DRV
Other Intervention Name(s)
Prezista®
Intervention Description
DRV 800 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
NRTI
Intervention Description
Participants will receive 2 investigator-selected 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 Outcome Measure Information:
Title
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
Description
Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).
Time Frame
Baseline; Week 24
Title
Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
Description
Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).
Time Frame
Baseline; Week 24
Title
Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
Description
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
Title
Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
Description
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
Title
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)
Description
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
Title
Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
Description
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.
Time Frame
Baseline; Week 24
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
Description
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (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
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
Description
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (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.
Time Frame
Baseline; Week 24
Title
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
Description
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.
Time Frame
Baseline; Weeks 2, 4, and 24
Title
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
Description
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.
Time Frame
Baseline; Weeks 2, 4, and 24
Title
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
Description
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Time Frame
Week 24
Title
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
Description
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)
Description
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
Title
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)
Description
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
Title
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)
Description
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
Title
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)
Description
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
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)
Description
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
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)
Description
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
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)
Description
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
Title
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)
Description
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
Title
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)
Description
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
Title
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)
Description
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
Title
Percentage of Participants Who Experienced Adverse Events (Cohort 1)
Description
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
Title
Percentage of Participants Who Experienced Adverse Events (Cohort 2)
Description
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
Title
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
Description
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
Title
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
Description
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
Title
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
Description
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).
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
Description
AUCtau was analyzed for Cohort 2 (treatment-experienced) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
Description
Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
Description
Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
Description
Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
Description
Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
Description
Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
Description
Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
Description
t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
Title
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
Description
t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.
Time Frame
Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Javier Szwarcberg, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Spectrum Medical Group
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
Health for Life Clinic
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72207
Country
United States
Facility Name
AHF Research Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Kaiser Permanente
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Peter J. Ruane, M.D., Inc.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
Facility Name
Anthony Mills, MD, Inc.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Orange Coast Medical Group
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
East Bay AIDS Center
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
01105
Country
United States
Facility Name
Metropolis Medical
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Yale University School of Medicine AIDS Program
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Whitman Walker Clinic
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20009
Country
United States
Facility Name
Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Therafirst Medical Center
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Broward Health
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33311
Country
United States
Facility Name
Gary J. Richmond.M.D.,P.A.
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33316
Country
United States
Facility Name
Midway Immunology and Research Center
City
Fort Pierce
State/Province
Florida
ZIP/Postal Code
34982
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
IDOCF/ValueHealthMD, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Infectious Disease Specialists of Atlanta
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Mercer University/ Mercer Medicine Clinical Research
City
Macon
State/Province
Georgia
ZIP/Postal Code
31201
Country
United States
Facility Name
Northstar Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
The Research Institute
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01105
Country
United States
Facility Name
Central West Clinical Research, Inc.
City
St.Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
ID Care
City
Hillsborough
State/Province
New Jersey
ZIP/Postal Code
08844
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Chelsea Village Medical
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Mount Sinai Downtown Comprehensive Health Program
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
AIDS Care
City
Rochester
State/Province
New York
ZIP/Postal Code
14607
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Southwest Infectious Disease Clinical Research, Inc.
City
Addison
State/Province
Texas
ZIP/Postal Code
75001
Country
United States
Facility Name
Tarrant County Infectious Disease Associates
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Therapeutic Concepts, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Taylor Square Private Clinic
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
Infectious Diseases Unit - The Alfred Hospital
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Facility Name
Holdsworth House Medical Practice
City
Sydney
ZIP/Postal Code
2010
Country
Australia
Facility Name
Landeskrankenhaus Graz West
City
Graz
ZIP/Postal Code
8020
Country
Austria
Facility Name
Otto Wagner Spital
City
Wien
ZIP/Postal Code
1140
Country
Austria
Facility Name
Sunnybrook Health Sciences Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N3M5
Country
Canada
Facility Name
Clinique Medicale du Quartier Latin
City
Montreal
ZIP/Postal Code
H2L5B1
Country
Canada
Facility Name
Instituto Dominicano de Estudio Virologicos
City
Santo Domingo
ZIP/Postal Code
99999
Country
Dominican Republic
Facility Name
Center for HIV and Hepatogastroenterology
City
Düsseldorf
ZIP/Postal Code
40237
Country
Germany
Facility Name
Hospital Civil de Guadalajara "Fray Antonio Alcalde"
City
Guadalajara
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Clinical Research Puerto Rico
City
San Juan
ZIP/Postal Code
00909
Country
Puerto Rico
Facility Name
HOPE Clinical Research
City
San Juan
ZIP/Postal Code
00909
Country
Puerto Rico
Facility Name
Brighton and Sussex University Hospitals NHS Trust
City
Brighton
ZIP/Postal Code
BN2 1ES
Country
United Kingdom
Facility Name
Barts & the London NHS Trust
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Homerton University Hospital
City
London
ZIP/Postal Code
SE5 0DJ
Country
United Kingdom
Facility Name
Guy's King's and St. Thomas' School of Medicine
City
London
ZIP/Postal Code
SE5 9RJ
Country
United Kingdom
Facility Name
St Stephen's AIDS Trust
City
London
ZIP/Postal Code
SW10 9NH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25397568
Citation
Fisher M, McDonald C, Moyle G, Martorell C, Ramgopal M, Laplante F, Curley J, Graham H, Tran-Muchowski C, Liu Y, Rhee M, Szwarcberg J. Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19824. doi: 10.7448/IAS.17.4.19824. eCollection 2014.
Results Reference
result
PubMed Identifier
25469527
Citation
Post FA, Winston J, Andrade-Villanueva JF, Fisher M, Liu Y, Beraud C, Abram ME, Graham H, Rhee MS, Cheng AK, Szwarcberg J; Study 118 Team. Elvitegravir/cobicistat/emtricitabine/tenofovir DF in HIV-infected patients with mild-to-moderate renal impairment. J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):310-3. doi: 10.1097/QAI.0000000000000476.
Results Reference
result
Learn more about this trial
Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
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