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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00892437
• Other study ID #: GS-US-216-0105
• Status: Completed
• Phase: Phase 2
• First received: April 30, 2009
• Last updated: January 15, 2016
• Start date: May 2009
• Est. completion date: January 2015

Study information

• Verified date: January 2016
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: January 2015
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

• HIV-1 Infection

Intervention

Drug:
• COBI
Cobicistat (COBI) 150 mg tablet administered orally once daily
• RTV
Ritonavir (RTV) 100 mg soft gelatin capsule administered orally once daily
• ATV
Atazanavir (ATV) 300 mg capsule administered orally once daily
• FTC/TDF
Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily
• COBI placebo
Placebo to match COBI administered orally once daily
• RTV placebo
Placebo to match RTV administered orally once daily

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Chase Brexton Health Services, Inc.	Baltimore	Maryland
United States	Be Well Medical Center	Berkley	Michigan
United States	AIDS Healthcare Foundation-Research Center	Beverly Hills	California
United States	Northstar Medical Center	Chicago	Illinois
United States	AIDS Arms/ Peabody Health Center	Dallas	Texas
United States	Nicholaos Bellos, MD, PA	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta (IDSA)	Decatur	Georgia
United States	Denver Infectious Disease Consultants, PLLC	Denver	Colorado
United States	Gary Richmond, MD, PA, Inc.	Fort Lauderdale	Florida
United States	Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Therapeutic Concepts, P.A.	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Health for Life Clinic, PLLC	Little Rock	Arkansas
United States	The Living Hope Foundation	Long Beach	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Orange Coast Medical Group	Newport Beach	California
United States	ValuehealthMD, LLC	Orlando	Florida
United States	Southwest Center for HIV/AIDS	Phoenix	Arizona
United States	David J. Shamblaw, MD Inc.	San Diego	California
United States	Metropolis Medical	San Francisco	California
United States	Southwest C.A.R.E. Center	Santa Fe	New Mexico
United States	TribalMed	Seattle	Washington
United States	Central West Healthcare	St. Louis	Missouri
United States	Southampton Healthcare, 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 Physicians Group	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the missing = failure method, where participants with missing data were considered to have failed to achieve the endpoint.	Week 24	No
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the missing = failure method.	Week 48	No
Secondary	Change From Baseline in HIV-1 RNA at Week 24	The change from baseline in log_10 HIV-1 RNA at Week 24 was analyzed.	Baseline to Week 24	No
Secondary	Change From Baseline in HIV-1 RNA at Week 48	The change from baseline in log_10 HIV-1 RNA at Week 48 was analyzed.	Baseline to Week 48	No
Secondary	Change From Baseline in CD4 Cell Count at Week 24	The change from baseline in CD4 cell count at Week 24 was analyzed.	Baseline to Week 24	No
Secondary	Change From Baseline in CD4 Cell Count at Week 48	The change from baseline in CD4 cell count at Week 48 was analyzed.	Baseline to Week 48	No