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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01363011
First received: May 11, 2011
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This study is to characterize the effect of Cobicistat based regimens on parameters of renal function in HIV infected patients with mild to moderate renal impairment, and also, to assess the safety and tolerability of those regimens in order to generate appropriate dosing recommendations.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
HIV Infections
Drug: EVG/COBI/FTC/TDF
Drug: COBI
Drug: ATV
Drug: DRV
Drug: NRTI
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change from baseline in estimated glomerular filtration rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of participants achieving virologic response (HIV-1 RNA < 50 copies/mL) [ Time Frame: Weeks 24, 48 and 96 ] [ Designated as safety issue: No ]
  • Long term effect of COBI-containing regimens on renal parameters [ Time Frame: Weeks 24, 48, and 96 ] [ Designated as safety issue: Yes ]
    Safety data regarding renal parameters will be summarized.

  • Incidence of adverse events and graded laboratory abnormalities [ Time Frame: Baseline to Week 96 plus 30 days ] [ Designated as safety issue: No ]
    All safety data will be summarized by treatment group.

  • Plasma pharmacokinetics (PK) parameters of COBI as measured by Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½. [ Time Frame: Baseline, Weeks, 2, 4, and 24 ] [ Designated as safety issue: No ]
    • Cmax is defined as the maximum observed concentration of drug in plasma
    • Tmax is defined as the time of Cmax
    • Clast is defined as the last observable concentration of drug
    • Tlast is defined as the time of Clast
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • λz is defined as the terminal elimination rate constant
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug


Estimated Enrollment: 100
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EVG/COBI/FTC/TDF
Participants will receive EVG/COBI/FTC/TDF STR for 96 weeks.
Drug: EVG/COBI/FTC/TDF
Cohort 1: Single tablet regimen of elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg
Other Name: Stribild®
Experimental: ATV/co or DRV/co
Participants will receive ATV/co or DRV/co, plus 2 NRTIs, for 96 weeks.
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 invesigator-selected nucleoside reverse transcriptase inhibitors (NRTIs), which may include abacavir (ABC), combivir, didanosine (DDI), emtricitabine (FTC), epzicom, lamivudine (3TC), tenofovir disoproxil fumarate (TDF), or truvada (TVD), administered according to prescribing information.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Cohort 1 (Treatment Naïve)

  • 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 (Pharmacoenhancer Switch)

  • Subjects must be receiving atazanavir (ATV) 300 mg/ritonavir (RTV) 100 mg plus 2 NRTIs OR darunavir (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)

Cohort 1 and Cohort 2

  • 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 upper limit of normal)
  • 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, non-invasive 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, atazanavir capsules or darunavir tablets or contraindicated for the 2 NRTIs as part of the Cohort 2 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363011

  Show 51 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Javier Szwarcberg, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01363011     History of Changes
Other Study ID Numbers: GS-US-236-0118
Study First Received: May 11, 2011
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV-1
Treatment Naive
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tenofovir disoproxil
Immunologic Deficiency Syndromes
Renal Insufficiency
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Kidney Diseases
Urologic Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 29, 2014