Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01363011




Registration number
NCT01363011
Ethics application status
Date submitted
11/05/2011
Date registered
1/06/2011
Date last updated
2/05/2016

Titles & IDs
Public title
Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
Scientific 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
Secondary ID [1] 0 0
GS-US-236-0118
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acquired Immunodeficiency Syndrome 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - E/C/F/TDF
Treatment: Drugs - COBI
Treatment: Drugs - ATV
Treatment: Drugs - DRV
Treatment: Drugs - NRTI

Experimental: E/C/F/TDF (Cohort 1) - 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.

Experimental: COBI+PI+2 NRTI (Cohort 2) - 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.


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

Treatment: Drugs: COBI
COBI 150 mg tablet administered with food orally once daily

Treatment: Drugs: ATV
ATV 300 mg tablet administered orally once daily

Treatment: Drugs: DRV
DRV 800 mg tablet administered orally once daily

Treatment: Drugs: NRTI
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
Timepoint [1] 0 0
Baseline; Week 24
Primary outcome [2] 0 0
Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
Timepoint [2] 0 0
Baseline; Week 24
Primary outcome [3] 0 0
Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
Timepoint [3] 0 0
Baseline; Week 24
Primary outcome [4] 0 0
Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
Timepoint [4] 0 0
Baseline; Week 24
Primary outcome [5] 0 0
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)
Timepoint [5] 0 0
Baseline; Week 24
Primary outcome [6] 0 0
Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
Timepoint [6] 0 0
Baseline; Week 24
Primary outcome [7] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
Timepoint [7] 0 0
Baseline; Week 24
Primary outcome [8] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
Timepoint [8] 0 0
Baseline; Week 24
Primary outcome [9] 0 0
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
Timepoint [9] 0 0
Baseline; Weeks 2, 4, and 24
Primary outcome [10] 0 0
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
Timepoint [10] 0 0
Baseline; Weeks 2, 4, and 24
Primary outcome [11] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
Timepoint [11] 0 0
Week 24
Primary outcome [12] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
Timepoint [12] 0 0
Week 24
Secondary outcome [1] 0 0
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)
Timepoint [1] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [2] 0 0
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)
Timepoint [2] 0 0
Baseline; Week 48
Secondary outcome [3] 0 0
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)
Timepoint [3] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [4] 0 0
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)
Timepoint [4] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [5] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)
Timepoint [5] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [6] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)
Timepoint [6] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [7] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)
Timepoint [7] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [8] 0 0
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)
Timepoint [8] 0 0
Baseline; Weeks 48 and 96
Secondary outcome [9] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)
Timepoint [9] 0 0
Weeks 48 and 96
Secondary outcome [10] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)
Timepoint [10] 0 0
Weeks 48 and 96
Secondary outcome [11] 0 0
Percentage of Participants Who Experienced Adverse Events (Cohort 1)
Timepoint [11] 0 0
Up to 147 weeks plus 30 days
Secondary outcome [12] 0 0
Percentage of Participants Who Experienced Adverse Events (Cohort 2)
Timepoint [12] 0 0
Up to 166 weeks plus 30 days
Secondary outcome [13] 0 0
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
Timepoint [13] 0 0
Up to 147 weeks plus 30 days
Secondary outcome [14] 0 0
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
Timepoint [14] 0 0
Up to 166 weeks plus 30 days
Secondary outcome [15] 0 0
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
Timepoint [15] 0 0
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.
Secondary outcome [16] 0 0
Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
Timepoint [16] 0 0
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.
Secondary outcome [17] 0 0
Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
Timepoint [17] 0 0
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.
Secondary outcome [18] 0 0
Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
Timepoint [18] 0 0
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.
Secondary outcome [19] 0 0
Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
Timepoint [19] 0 0
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.
Secondary outcome [20] 0 0
Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
Timepoint [23] 0 0
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.
Secondary outcome [24] 0 0
Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
Timepoint [24] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2015
Sample size
Target
Accrual to date
Final
106
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Taylor Square Private Clinic - Darlinghurst
Recruitment hospital [2] 0 0
Infectious Diseases Unit - The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Austria
State/province [16] 0 0
Graz
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Montreal
Country [20] 0 0
Dominican Republic
State/province [20] 0 0
Santo Domingo
Country [21] 0 0
Germany
State/province [21] 0 0
Düsseldorf
Country [22] 0 0
Mexico
State/province [22] 0 0
Guadalajara
Country [23] 0 0
Puerto Rico
State/province [23] 0 0
San Juan
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Brighton
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Javier Szwarcberg, MD
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents


Results are available at https://clinicaltrials.gov/study/NCT01363011