Clinical trial NCT01363011: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: HIV-1
Treatment Naive
Treatment Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-06-01
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
timeFrame: Baseline; Week 24
measure: 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)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
timeFrame: Baseline; Week 24
measure: Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
timeFrame: Baseline; Weeks 2, 4, and 24
measure: Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
timeFrame: Baseline; Weeks 2, 4, and 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)
timeFrame: Baseline; Week 48
measure: Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)
timeFrame: Baseline; Weeks 48 and 96
measure: Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)
timeFrame: Baseline; Weeks 48 and 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)
timeFrame: Weeks 48 and 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)
timeFrame: Weeks 48 and 96
measure: Percentage of Participants Who Experienced Adverse Events (Cohort 1)
timeFrame: Up to 147 weeks plus 30 days
measure: Percentage of Participants Who Experienced Adverse Events (Cohort 2)
timeFrame: Up to 166 weeks plus 30 days
measure: Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
timeFrame: Up to 147 weeks plus 30 days
measure: Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
timeFrame: Up to 166 weeks plus 30 days
measure: Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
timeFrame: 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.
measure: Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
timeFrame: 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.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Little Rock
country: United States
facility: Health for Life Clinic
state: Arkansas
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, M.D., Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Mills, MD, Inc.
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine AIDS Program
state: Connecticut
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond.M.D.,P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: IDOCF/ValueHealthMD, LLC
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University/ Mercer Medicine Clinical Research
state: Georgia
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: St.Louis
country: United States
facility: Central West Clinical Research, Inc.
state: Missouri
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Chelsea Village Medical
state: New York
city: New York
country: United States
facility: Mount Sinai Downtown Comprehensive Health Program
state: New York
city: Rochester
country: United States
facility: AIDS Care
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Addison
country: United States
facility: Southwest Infectious Disease Clinical Research, Inc.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic
city: Melbourne
country: Australia
facility: Infectious Diseases Unit - The Alfred Hospital
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
city: Graz
country: Austria
facility: Landeskrankenhaus Graz West
city: Wien
country: Austria
facility: Otto Wagner Spital
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale du Quartier Latin
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudio Virologicos
city: Düsseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara "Fray Antonio Alcalde"
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts & the London NHS Trust
city: London
country: United Kingdom
facility: Homerton University Hospital
city: London
country: United Kingdom
facility: Guy's King's and St. Thomas' School of Medicine
city: London
country: United Kingdom
facility: St Stephen's AIDS Trust
Study officials:
affiliation: Gilead Sciences
name: Javier Szwarcberg, MD
role: STUDY_DIRECTOR
References:
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.
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.