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

NCT01363011 | Completed Phase 3 Results

• 1 other identifier: GS-US-236-0118
• Study Type: interventional
• Target: 106
• Locations: 8 countries
• Sites: 48

Brief Summary

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.

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Keywords

HIV-1; Treatment Naive; Treatment Experienced

Outcome Measures

Primary Outcomes (12)

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)

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

  Baseline; Week 24

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

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

  Baseline; Week 24

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

  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.

  Baseline; Week 24

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

  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.

  Baseline; Week 24

• 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)

  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.

  Baseline; Week 24

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

  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.

  Baseline; Week 24

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

  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.

  Baseline; Week 24

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

  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.

  Baseline; Week 24

• Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)

  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.

  Baseline; Weeks 2, 4, and 24

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

  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.

  Baseline; Weeks 2, 4, and 24

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

  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.

  Week 24

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

  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.

  Week 24

Secondary Outcomes (24)

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

  Baseline; Weeks 48 and 96

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

  Baseline; Week 48

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

  Baseline; Weeks 48 and 96

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

  Baseline; Weeks 48 and 96

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

  Baseline; Weeks 48 and 96

Study Arms (2)

E/C/F/TDF (Cohort 1)

EXPERIMENTAL

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.

Drug: E/C/F/TDF

COBI+PI+2 NRTI (Cohort 2)

EXPERIMENTAL

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.

Drug: COBI; Drug: ATV; Drug: DRV; Drug: NRTI

Interventions

E/C/F/TDF DRUG

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

Also known as: Stribild®

E/C/F/TDF (Cohort 1)

COBI DRUG

COBI 150 mg tablet administered with food orally once daily

Also known as: Tybost®

COBI+PI+2 NRTI (Cohort 2)

ATV DRUG

ATV 300 mg tablet administered orally once daily

Also known as: Reyataz®

COBI+PI+2 NRTI (Cohort 2)

DRV DRUG

DRV 800 mg tablet administered orally once daily

Also known as: Prezista®

COBI+PI+2 NRTI (Cohort 2)

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.

COBI+PI+2 NRTI (Cohort 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (51)

Spectrum Medical Group

Phoenix, Arizona, 85012, United States

Location

Health for Life Clinic

Little Rock, Arkansas, 72207, United States

Location

AHF Research Center

Beverly Hills, California, 90211, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

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

Los Angeles, California, 90036, United States

Location

Anthony Mills, MD, Inc.

Los Angeles, California, 90069, United States

Location

Orange Coast Medical Group

Newport Beach, California, 92663, United States

Location

East Bay AIDS Center

Oakland, California, 94609, United States

Location

University of California, Davis

Sacramento, California, 01105, United States

Location

Metropolis Medical

San Francisco, California, 94115, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine AIDS Program

New Haven, Connecticut, 06520, United States

Location

Whitman Walker Clinic

Washington D.C., District of Columbia, 20009, United States

Location

Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Therafirst Medical Center

Fort Lauderdale, Florida, 33308, United States

Location

Broward Health

Fort Lauderdale, Florida, 33311, United States

Location

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

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

IDOCF/ValueHealthMD, LLC

Orlando, Florida, 32806, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Mercer University/ Mercer Medicine Clinical Research

Macon, Georgia, 31201, United States

Location

Northstar Medical Center

Chicago, Illinois, 60657, United States

Location

The Research Institute

Springfield, Massachusetts, 01105, United States

Location

Central West Clinical Research, Inc.

St Louis, Missouri, 63108, United States

Location

ID Care

Hillsborough, New Jersey, 08844, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Chelsea Village Medical

New York, New York, 10011, United States

Location

Mount Sinai Downtown Comprehensive Health Program

New York, New York, 10011, United States

Location

AIDS Care

Rochester, New York, 14607, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Southwest Infectious Disease Clinical Research, Inc.

Addison, Texas, 75001, United States

Location

Tarrant County Infectious Disease Associates

Fort Worth, Texas, 76104, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

Taylor Square Private Clinic

Darlinghurst, 2010, Australia

Location

Infectious Diseases Unit - The Alfred Hospital

Melbourne, 3004, Australia

Location

Holdsworth House Medical Practice

Sydney, 2010, Australia

Location

Landeskrankenhaus Graz West

Graz, 8020, Austria

Location

Otto Wagner Spital

Vienna, 1140, Austria

Location

Sunnybrook Health Sciences Center

Toronto, Ontario, M4N3M5, Canada

Location

Clinique Medicale du Quartier Latin

Montreal, H2L5B1, Canada

Location

Instituto Dominicano de Estudio Virologicos

Santo Domingo, 99999, Dominican Republic

Location

Center for HIV and Hepatogastroenterology

Düsseldorf, 40237, Germany

Location

Hospital Civil de Guadalajara "Fray Antonio Alcalde"

Guadalajara, 44280, Mexico

Location

Clinical Research Puerto Rico

San Juan, 00909, Puerto Rico

Location

HOPE Clinical Research

San Juan, 00909, Puerto Rico

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, BN2 1ES, United Kingdom

Location

Barts & the London NHS Trust

London, E1 1BB, United Kingdom

Location

Homerton University Hospital

London, SE5 0DJ, United Kingdom

Location

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

London, SE5 9RJ, United Kingdom

Location

St Stephen's AIDS Trust

London, SW10 9NH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25397568 RESULT

• 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.

  PMID: 25469527 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Cobicistat; Atazanavir Sulfate; Darunavir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Sulfonamides; Amides; Sulfones; Furans

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Javier Szwarcberg, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: June 1, 2011
• Study Start: May 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2015
• Last Updated: May 2, 2016
• Results First Posted: October 31, 2014

Record last verified: 2016-03

Locations

US (34); ME (1); AU (2); CA (2); DO (1); DE (1); PR (2); GB (5)