Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults

HIV Infections Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565850
• Other study ID #: GS-US-299-0102
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2012
• Last updated: February 27, 2014
• Start date: April 2012
• Est. completion date: February 2014

Study information

• Verified date: February 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the efficacy darunavir/cobicistat/emtricitabine/GS-7340 (D/C/F/TAF) single-tablet regimen (STR) versus darunavir (DRV)+cobicistat (COBI)+emtricitabine(FTC)/tenofuvir disoproxil fumarate (TDF) in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 24.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: February 2014
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult (= 18 years) males or non-pregnant females

• Ability to understand and sign a written informed consent form

• General medical condition which does not interfere with the assessments and the completion of the trial

• Plasma HIV-1 RNA levels = 5,000 copies/mL

• CD4+ cell count > 50 cells/µL

• Treatment Naïve: No prior use of any approved or experimental anti-HIV drug for any length of time

• Screening genotype report must show sensitivity to DRV, TDF and FTC

• Normal ECG

• Adequate renal function: Estimated glomerular filtration rate = 70 mL/min according to the Cockcroft Gault formula

• Hepatic transaminases = 2.5 x upper limit of normal (ULN)

• Total bilirubin = 1.5 mg/dL

• Serum amylase = 5 x ULN

• Adequate hematologic function

• Normal thyroid-stimulating hormone (TSH)

• Females of childbearing potential must have a negative serum pregnancy test

• 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 drugs

• Female subjects who are postmenopausal must have documentation of cessation of menses for = 12 months and hormonal failure

• Female subjects who have stopped menstruating for = 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test

• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product

Exclusion Criteria:

• A new AIDS defining condition diagnosed within the 30 days prior to screening

• Hepatitis B surface Antigen positive

• Hepatitis C Antibody positive

• Proven acute hepatitis in the 30 days prior to study entry

• Have a history or experiencing decompensated cirrhosis

• Current alcohol or substance use that potentially interferes with study compliance

• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma

• Females who are breastfeeding

• Positive serum pregnancy test (female of childbearing potential)

• Female subjects who utilize non-estrogen hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing

• Have an implanted defibrillator or pacemaker

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline

• Participation in any other clinical trial without prior approval is prohibited while participating in this trial

• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with darunavir and cobicistat

• Note: Darunavir is a sulfonamide. Subjects who previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and darunavir has been identified in patients participating in Phase 2 and Phase 3 trials.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• D/C/F/TAF
DRV 800 mg/COBI 150 mg/FTC 200 mg/TAF 10 mg STR administered orally once daily
• DRV
DRV 2x400 mg tablets administered orally once daily
• COBI
COBI 150 mg tablet administered orally once daily
• FTC/TDF
FTC 200 mg/TDF 300 mg tablet administered orally once daily
• Placebo to match D/C/F/TAF
Placebo to match D/C/F/TAF administered orally once daily
• Placebo to match DRV
Placebo to match DRV administered orally once daily
• Placebo to match COBI
Placebo to match COBI administered orally once daily
• Placebo to match FTC/TDF
Placebo to match FTC/TDF administered orally once daily

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
United States	CARE-ID	Annandale	Virginia
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Community Research Initiative (CRI)	Boston	Massachusetts
United States	ID Consultants, P.A.	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	University of South Carolina School of Medicine Division of Infectious Disease	Columbia	South Carolina
United States	Southwest Infectious Disease Clinical Research Inc	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Denver Infectious Disease Consultants, PLLC	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Gordon E. Crofoot, MD., PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD, Inc	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	Mercer University Mercer Medicine	Macon	Georgia
United States	North Shore University Hospital / Division of Infectious Diseases	Manhasset	New York
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Weill Cornell Medical College	New York	New York
United States	Orange Coast Medical Group	Newport Beach	California
United States	Alta Bates Summit Medical Center, East Bay AIDS Center	Oakland	California
United States	IDOCF/ValuhealthMD, LLC	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	TPMG--Clinical Trials Unit	San Francisco	California
United States	Peter Shalit, M.D.	Seattle	Washington
United States	Central West Clinical Research Inc	St. Louis	Missouri
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24		Week 24	No
Secondary	Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48		Week 48	No
Secondary	Change from baseline in log10 HIV-1 RNA and in CD4+ cell count at Weeks 24 and 48		Weeks 24 and 48	No