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

NCT ID: NCT01363011

Last Updated: 2016-05-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2015-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Acquired Immunodeficiency Syndrome HIV Infections

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

E/C/F/TDF

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

COBI

Intervention Type DRUG

COBI 150 mg tablet administered with food orally once daily

ATV

Intervention Type DRUG

ATV 300 mg tablet administered orally once daily

DRV

Intervention Type DRUG

DRV 800 mg tablet administered orally once daily

NRTI

Intervention Type 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.

Interventions

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E/C/F/TDF

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

Intervention Type DRUG

COBI

COBI 150 mg tablet administered with food orally once daily

Intervention Type DRUG

ATV

ATV 300 mg tablet administered orally once daily

Intervention Type DRUG

DRV

DRV 800 mg tablet administered orally once daily

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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Stribild® Tybost® Reyataz® Prezista®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Javier Szwarcberg, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Spectrum Medical Group

Phoenix, Arizona, United States

Site Status

Health for Life Clinic

Little Rock, Arkansas, United States

Site Status

AHF Research Center

Beverly Hills, California, United States

Site Status

Kaiser Permanente

Los Angeles, California, United States

Site Status

Peter J. Ruane, M.D., Inc.

Los Angeles, California, United States

Site Status

Anthony Mills, MD, Inc.

Los Angeles, California, United States

Site Status

Orange Coast Medical Group

Newport Beach, California, United States

Site Status

East Bay AIDS Center

Oakland, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

Metropolis Medical

San Francisco, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Yale University School of Medicine AIDS Program

New Haven, Connecticut, United States

Site Status

Whitman Walker Clinic

Washington D.C., District of Columbia, United States

Site Status

Medical Faculty Associates

Washington D.C., District of Columbia, United States

Site Status

Therafirst Medical Center

Fort Lauderdale, Florida, United States

Site Status

Broward Health

Fort Lauderdale, Florida, United States

Site Status

Gary J. Richmond.M.D.,P.A.

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

IDOCF/ValueHealthMD, LLC

Orlando, Florida, United States

Site Status

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Site Status

Mercer University/ Mercer Medicine Clinical Research

Macon, Georgia, United States

Site Status

Northstar Medical Center

Chicago, Illinois, United States

Site Status

The Research Institute

Springfield, Massachusetts, United States

Site Status

Central West Clinical Research, Inc.

St Louis, Missouri, United States

Site Status

ID Care

Hillsborough, New Jersey, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Chelsea Village Medical

New York, New York, United States

Site Status

Mount Sinai Downtown Comprehensive Health Program

New York, New York, United States

Site Status

AIDS Care

Rochester, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Southwest Infectious Disease Clinical Research, Inc.

Addison, Texas, United States

Site Status

Tarrant County Infectious Disease Associates

Fort Worth, Texas, United States

Site Status

Therapeutic Concepts, PA

Houston, Texas, United States

Site Status

Taylor Square Private Clinic

Darlinghurst, , Australia

Site Status

Infectious Diseases Unit - The Alfred Hospital

Melbourne, , Australia

Site Status

Holdsworth House Medical Practice

Sydney, , Australia

Site Status

Landeskrankenhaus Graz West

Graz, , Austria

Site Status

Otto Wagner Spital

Vienna, , Austria

Site Status

Sunnybrook Health Sciences Center

Toronto, Ontario, Canada

Site Status

Clinique Medicale du Quartier Latin

Montreal, , Canada

Site Status

Instituto Dominicano de Estudio Virologicos

Santo Domingo, , Dominican Republic

Site Status

Center for HIV and Hepatogastroenterology

Düsseldorf, , Germany

Site Status

Hospital Civil de Guadalajara "Fray Antonio Alcalde"

Guadalajara, , Mexico

Site Status

Clinical Research Puerto Rico

San Juan, , Puerto Rico

Site Status

HOPE Clinical Research

San Juan, , Puerto Rico

Site Status

Brighton and Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Site Status

Barts & the London NHS Trust

London, , United Kingdom

Site Status

Homerton University Hospital

London, , United Kingdom

Site Status

Guy's King's and St. Thomas' School of Medicine

London, , United Kingdom

Site Status

St Stephen's AIDS Trust

London, , United Kingdom

Site Status

Countries

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United States Australia Austria Canada Dominican Republic Germany Mexico Puerto Rico United Kingdom

References

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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.

Reference Type RESULT
PMID: 25397568 (View on PubMed)

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.

Reference Type RESULT
PMID: 25469527 (View on PubMed)

Other Identifiers

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GS-US-236-0118

Identifier Type: -

Identifier Source: org_study_id

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