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Completed

NCT Number: NCT01363011

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 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.

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Key information

Conditions

Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Taylor Square Private Clinic, Darlinghurst, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

E/C/F/TDF

Drug

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

Other names: Stribild®

COBI

Drug

COBI 150 mg tablet administered with food orally once daily

Other names: Tybost®

ATV

Drug

ATV 300 mg tablet administered orally once daily

Other names: Reyataz®

DRV

Drug

DRV 800 mg tablet administered orally once daily

Other names: Prezista®

NRTI

Drug

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 outcomes

  1. 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

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

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

    Time frame: Baseline; Week 24

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

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

    Time frame: Baseline; Week 24

    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.

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

    Time frame: Baseline; Week 24

    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.

  5. 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

    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.

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

    Time frame: Baseline; Week 24

    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.

  7. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)

    Time frame: Baseline; Week 24

    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.

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

    Time frame: Baseline; Week 24

    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.

  9. 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

    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.

  10. Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)

    Time frame: Baseline; Weeks 2, 4, and 24

    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.

  11. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)

    Time frame: Week 24

    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.

  12. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)

    Time frame: Week 24

    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 outcomes

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Week 48

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Baseline; Weeks 48 and 96

    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.

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

    Time frame: Weeks 48 and 96

    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.

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

    Time frame: Weeks 48 and 96

    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.

  11. Percentage of Participants Who Experienced Adverse Events (Cohort 1)

    Time frame: Up to 147 weeks plus 30 days

    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.

  12. Percentage of Participants Who Experienced Adverse Events (Cohort 2)

    Time frame: Up to 166 weeks plus 30 days

    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.

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

    Time frame: Up to 147 weeks plus 30 days

    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.

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

    Time frame: Up to 166 weeks plus 30 days

    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.

  15. 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.

    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).

  16. 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.

    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).

  17. 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.

    Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.

  18. 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.

    Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.

  19. 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.

    Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.

  20. 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.

    Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.

  21. 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.

    Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.

  22. 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.

    Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.

  23. 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.

    t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.

  24. 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.

    t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2013
Study completion
2015
First posted
Jun 1, 2011
Registry last updated
May 2, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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