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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01363011
First received: May 11, 2011
Last updated: February 25, 2015
Last verified: February 2015

May 11, 2011
February 25, 2015
May 2011
January 2013   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Weeks 2, 4, and 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline; Weeks 2, 4, and 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.
primary endpoint is the change from baseline to Week 24 in estimated creatinine clearance [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01363011 on ClinicalTrials.gov Archive Site
  • Change From Baseline in eGFR-CG at Week 48 (Cohort 1) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CG at Week 48 was analyzed in Cohort 1 (treatment-naive).
  • Change From Baseline in eGFR-CG at Week 48 (Cohort 2) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CG at Week 48 was analyzed in Cohort 2 (treatment-experienced).
  • Change From Baseline in eGFR-MDRD at Week 48 (Cohort 1) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-MDRD at Week 48 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 48 (Cohort 2) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-MDRD at Week 48 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 at Week 48 (Cohort 1) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 48 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 at Week 48 (Cohort 2) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 48 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 48 (Cohort 1) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 48 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 48 (Cohort 2) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 48 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 (Cohort 1) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 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 48 (Cohort 2) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
  • Percentage of Participants Who Experienced Adverse Events (Cohort 1) [ Time Frame: Up to 48 weeks plus 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 48 weeks plus 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 48 weeks plus 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 48 weeks plus 30 days ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.
  • Plasma Pharmacokinetics of COBI: Tmax (Cohort 2) [ 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. ] [ Designated as safety issue: No ]
    Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.
  • Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.
The proportion of subjects achieving virologic response at Weeks 24 and 48 (HIV-1 RNA < 50 copies/mL) [ Time Frame: 24 & 48 Weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
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

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.

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Drug: 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.
    Other Name: Stribild®
  • Drug: COBI
    Cobicistat (COBI, /co) 150 mg tablet administered with food orally once daily
    Other Name: Tybost®
  • Drug: ATV
    Atazanavir (ATV) 300 mg tablet administered orally once daily
    Other Name: Reyataz®
  • Drug: DRV
    Darunavir (DRV) 800 mg tablet administered orally once daily
    Other Name: Prezista®
  • Drug: 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.
  • Experimental: Cohort 1
    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.
    Intervention: Drug: Stribild
  • Experimental: 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 COBI, and continuing their existing protease inhibitor (PI; either ATV or DRV)/2 NRTI regimen for up to 96 weeks.
    Interventions:
    • Drug: COBI
    • Drug: ATV
    • Drug: DRV
    • Drug: NRTI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
106
February 2015
January 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Canada,   Dominican Republic,   Germany,   Mexico,   Puerto Rico,   United Kingdom
 
NCT01363011
GS-US-236-0118
No
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Javier Szwarcberg, MD Gilead Sciences
Gilead Sciences
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP