Clinical trial NCT00892437: Safety and Efficacy of Cobicistat-boosted Atazanavir Compared to Ritonavir-boosted Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Official title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of GS-9350-boosted Atazanavir (ATV/GS-9350) Compared to Ritonavir-boosted Atazanavir (ATV/r) in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: HIV
HIV-1
Antiretroviral Treatment-Naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2009-05-04
Enrollment: 85
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 study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adults.

Participants will be randomized in a 2:1 ratio. 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, at which point all participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive ATV+COBI+FTC/TDF until COBI tablets become commercially available, or until Gilead Sciences elects to terminate the study.


Eligibility criteria: Inclusion Criteria:

* Ability to understand and sign a written informed consent form
* Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
* No prior use of any approved or experimental anti-HIV drug
* Normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
* Adequate renal function (estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft-Gault formula)
* Hepatic transaminases ≤ 2.5 × upper limit of normal
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Cluster of differentiation 4 (CD4) cell count \> 50 cells/µL
* Serum amylase ≤ 1.5 × ULN (subjects with serum amylase \>1.5 × ULN remained eligible if serum lipase is ≤ 1.5 × ULN)
* Normal thyroid-stimulating hormone
* Negative serum pregnancy test (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 30 days following the last dose of study drugs
* Age ≥ 18 years
* Life expectancy ≥ 1 year

Exclusion Criteria:

* New AIDS-defining condition diagnosed within the 30 days prior to screening
* Documented drug resistance to nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or primary PI 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 (female of childbearing potential)
* Vaccinated within 90 days of study dosing
* History or family history of Long QT Syndrome or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30 years
* Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
* Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) interval at screening (eg, a prolongation of the QTcF interval of greater than 450 msec for males and greater than 470 msec for females)
* PR interval greater than or equal to 200 msec or less than or equal to 120 msec on ECG at screening
* QRS greater than or equal to 120 msec on ECG at screening
* Implanted defibrillator or pacemaker
* Subjects receiving ongoing therapy with any disallowed medications
* Current alcohol or substance use judged to potentially interfere with subject 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 ATV, RTV, FTC, or TDF
* Any known allergies to the excipients of ATV capsules, RTV capsules, COBI tablets or FTC/TDF tablets
* Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
measure: Change From Baseline in HIV-1 RNA at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in HIV-1 RNA at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in 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
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Center for HIV/AIDS
state: Arizona
city: Little Rock
country: United States
facility: Health for Life Clinic, PLLC
state: Arkansas
city: Beverly Hills
country: United States
facility: AIDS Healthcare Foundation-Research Center
state: California
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: San Diego
country: United States
facility: David J. Shamblaw, MD Inc.
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: Denver
country: United States
facility: Denver Infectious Disease Consultants, PLLC
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: 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: ValuehealthMD, LLC
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
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: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: St. Louis
country: United States
facility: Central West Healthcare
state: Missouri
city: St. Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest C.A.R.E. Center
state: New Mexico
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: Houston
country: United States
facility: Therapeutic Concepts, P.A.
state: Texas
city: Seattle
country: United States
facility: TribalMed
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Marshall Fordyce, MD
role: STUDY_CHAIR
References:
citation: Elion R, Cohen C, Gathe J, Shalit P, Hawkins T, Liu HC, Mathias AA, Chuck SL, Kearney BP, Warren DR; GS-US-216-0105 Study Team. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS. 2011 Sep 24;25(15):1881-6. doi: 10.1097/QAD.0b013e32834b4d48.