Safety and Efficacy of GS-9350-Boosted Atazanavir Compared to Ritonavir-Boosted Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00892437

Purpose

The objective of this study is to evaluate the safety and efficacy of a regimen containing GS-9350-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected, antiretroviral treatment-naive adult subjects.

Condition	Intervention	Phase
HIV-1 Infection	Drug: 150 mg tablet GS- 9350 Drug: ritonavir 100 mg capsule Drug: atazanavir 300 mg capsule Drug: emtricitabine/tenofovir DF 200/300 mg tablet Drug: ritonavir placebo Drug: GS-9350 placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Ritonavir BMS 232632 Tenofovir disoproxil Tenofovir Disoproxil Fumarate Atazanavir sulfate Truvada

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA less than 50 copies/mL at week 24. [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The secondary efficacy endpoint is the proportion of subjects with HIV-1 RNA less than 50 copies/mL at week 48. [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	75
Study Start Date:	June 2009
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental GS-9350 150 mg QD + ritonavir placebo QD + atazanavir 300 mg QD + single tablet FTC/TDF 200/300 mg QD (n = 50)	Drug: 150 mg tablet GS- 9350 Drug: atazanavir 300 mg capsule Drug: emtricitabine/tenofovir DF 200/300 mg tablet Drug: ritonavir placebo All drugs will be administered orally, once daily with food at approximately the same time each day.
2: Active Comparator Ritonavir 100 mg QD + GS-9350 placebo QD + atazanavir 300 mg QD + single tablet FTC/TDF 200/300 mg QD (n = 25)	Drug: ritonavir 100 mg capsule Drug: atazanavir 300 mg capsule Drug: emtricitabine/tenofovir DF 200/300 mg tablet Drug: GS-9350 placebo All drugs will be administered orally, once daily with food at approximately the same time each day.

Detailed Description:

Double-blinded, multicenter, randomized, active-controlled study to assess the safety and efficacy of a regimen containing ATV/GS-9350 plus FTC/TDF versus ATV/r plus FTC/TDF in HIV-1 infected, antiretroviral treatment-naive adult subjects.

Subjects will be randomized in a 2:1 ratio to one of the following two treatment arms:

Treatment Arm 1: GS-9350 150 mg QD + ritonavir placebo QD + atazanavir 300 mg QD + single tablet FTC/TDF 200/300 mg QD (n = 50)

Treatment Arm 2: Ritonavir 100 mg QD + GS-9350 placebo QD + atazanavir 300 mg QD + single tablet FTC/TDF 200/300 mg QD (n = 25)

Randomization will be stratified by HIV-1 RNA level (less than or equal to 100,000 copies/mL or greater than 100,000 copies/mL) at screening.

After Week 48, subjects will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded, at which point all subjects will return for an Unblinding Visit and will be given the option to participate in an Open-Label Rollover Extension and receive GS-9350-boosted atazanavir, and Truvada® until GS-9350 tablets become commercially available, or until Gilead Sciences elects to terminate the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Plasma HIV-1 RNA levels greater than or equal to 5,000 copies/mL
No prior use of any approved or experimental anti-HIV drug
Normal ECG
Adequate renal function
Hepatic transaminases less than or equal to 2.5 x upper limit of normal
Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
Adequate hematologic function
CD4+ cell count greater than 50 cells/µL
Serum amylase less than or equal to 1.5 x ULN
Normal TSH
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 greater than or equal to 18 years
Life expectancy greater than or equal to 1 year
Ability to understand and sign a written informed consent form

Exclusion Criteria:

New AIDS defining condition diagnosed within the 30 days prior to screening
Documented drug resistance to NRTIs, NNRTIs, or primary PI resistance mutation(s)
Hepatitis B surface Antigen (HBsAg) positive
Hepatitis C Antibody positive
Subjects experiencing cirrhosis
Subjects experiencing ascites
Subjects 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
Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
Prolonged QTcF interval at screening (e.g., 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 (KS), basal cell carcinoma, or resected, non-invasive 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 atazanavir, ritonavir, emtricitabine, or tenofovir disoproxil fumarate
Any known allergies to the excipients of atazanavir capsules, ritonavir capsules, GS-9350 tablets or Truvada(R) (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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892437

Show 44 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Chair:

Steven Chuck, MD

Gilead Sciences

More Information

No publications provided

Responsible Party:	Gilead Sciences, Inc. ( Steven Chuck, MD )
Study ID Numbers:	GS-US-216-0105
Study First Received:	April 30, 2009
Last Updated:	June 18, 2009
ClinicalTrials.gov Identifier:	NCT00892437 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

HIV
HIV-1
Antiretroviral Treatment-Naive

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Atazanavir
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions

Reverse Transcriptase Inhibitors
Protease Inhibitors
Emtricitabine
Anti-Retroviral Agents
Ritonavir
Therapeutic Uses
Tenofovir
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil

ClinicalTrials.gov processed this record on February 08, 2010