Clinical trial NCT00869557: Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults
Official title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Atripla® (Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
HIV Infections
Keywords: HIV
HIV-1
Antiretroviral Treatment-Naive
treatment naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2009-03-26
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this double-blinded, multicenter, randomized, active-controlled study is to evaluate the safety and efficacy of Stribild, a single-tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adult participants. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs.

Participants will be randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or \> 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded (Week 60), at which point all participants will attend an Unblinding Visit and be given the option to participate in an open-label rollover extension (the extension is scheduled to be open until Stribild becomes commercially available, or until Gilead Sciences elects to terminate the study).


Eligibility criteria: Inclusion Criteria:

* Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
* No prior use of any approved or experimental anti-HIV drug
* Normal electrocardiogram (ECG)
* Adequate renal function: estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula
* Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Cluster determinant 4 (CD4) cell count \> 50 cells/µL
* Serum amylase ≤ 1.5 x ULN
* Normal thyroid-stimulating hormone
* Negative serum pregnancy test (for females of childbearing potential only)
* Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drugs
* Life expectancy ≥ 1 year
* Ability to understand and sign a written informed consent form

Exclusion Criteria:

* New acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
* Documented drug resistance to nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitors or primary protease inhibitor resistance mutation(s)
* Hepatitis B surface antigen positive
* Hepatitis C antibody positive
* Participants experiencing cirrhosis
* Participants experiencing ascites
* Participants experiencing encephalopathy
* Females who are breastfeeding
* Positive serum pregnancy test (for females of childbearing potential)
* Vaccinated within 90 days of study dosing
* History or family history of Long QT Syndrome or family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30
* Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
* Prolonged QTcF interval at screening
* PR interval ≥ 200 msec or ≤ 120 msec on ECG at screening
* QRS ≥ 120 msec on ECG at screening
* Implanted defibrillator or pacemaker
* Participants receiving ongoing therapy with any disallowed medications
* Current alcohol or substance use judged to potentially interfere with participant study compliance
* History of or ongoing malignancy (including untreated carcinoma in situ) 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
* Participation in any other clinical trial without prior approval
* Medications contraindicated for use with EFV, EVG, COBI, FTC, or TDF
* Any known allergies to the excipients of Atripla or Stribild tablets
* Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements

Primary outcomes:
measure: The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
timeFrame: Week 48
measure: Change From Baseline in HIV-1 RNA (log_10 Copies/mL)
timeFrame: Baseline to Weeks 24 and 48
measure: Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline to Week 48
measure: The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL
timeFrame: Baseline to Weeks 24 and 48
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Health for Life Clinic, PLLC
state: Arkansas
city: Long Beach
country: United States
facility: The Living Hope Foundation
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: Denver
country: United States
facility: Apex Research Institute
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates PC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward Health
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Infectious Disease of Central Florida
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta (IDSA)
state: Georgia
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Chase Brexton Health Services, Inc.
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: St. Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Santa Fe
country: United States
facility: Southwest C.A.R.E. Center
state: New Mexico
city: New York
country: United States
facility: Chelsea Village Medical
state: New York
city: New York
country: United States
facility: Ricky K. Hsu, MD, PC
state: New York
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Dallas
country: United States
facility: Nicholaos Bellos, MD, PA
state: Texas
city: Dallas
country: United States
facility: AIDS Arms/ Peabody Health Center
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD, PA
state: Texas
city: Seattle
country: United States
facility: TribalMed
state: Washington
Study officials:
References:
citation: Cohen C, Elion R, Ruane P, Shamblaw D, DeJesus E, Rashbaum B, Chuck SL, Yale K, Liu HC, Warren DR, Ramanathan S, Kearney BP. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS. 2011 Mar 27;25(6):F7-12. doi: 10.1097/QAD.0b013e328345766f.