Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 (QUAD) Versus Atripla(R) in HIV Infected, Antiretroviral Treatment-Naive Adults - Full Text View

Sponsor:	Gilead Sciences
Information provided by (Responsible Party):	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00869557

Purpose

The objective of this study is to evaluate the safety and efficacy of a single tablet regimen containing fixed doses of elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS 9350 versus Atripla in HIV 1 infected, antiretroviral treatment-naive adult subjects.

This new QUAD tablet of elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS 9350 could offer an alternative fixed-dose regimen for patients who cannot tolerate Atripla or are women of childbearing potential (due to the potential teratogenecity of efavirenz, a component of Atripla).

Condition	Intervention	Phase
HIV-1 Infection HIV Infections	Drug: Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Drug: Atripla	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 (QUAD) Versus Atripla(R) Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg) in HIV 1 Infected, Antiretroviral Treatment-Naive Adults

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Tenofovir Efavirenz Tenofovir disoproxil Tenofovir Disoproxil Fumarate GS 9137 Atripla

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 ]

Enrollment:	71
Study Start Date:	April 2009
Estimated Study Completion Date:	June 2012
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Fixed-dose combination tablet of elvitegravir (EVG) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg/GS 9350 150 mg QD + Placebo for Atripla QHS (n=50)	Drug: Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Elvitegravir/emtricitabine/tenofovir DF/GS 9350 and matching placebo will be administered orally, one tablet, once daily with food at approximately the same time each day.
Active Comparator: 2 Atripla QHS + Placebo for fixed-dose combination tablet of elvitegravir (EVG) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg/GS 9350 150 mg QD (n=25)	Drug: Atripla Atripla and matching placebo will be administered orally, one tablet, once daily, on an empty stomach prior to bedtime and at approximately the same time each day. Other Name: Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg

Detailed Description:

Double-blinded, multicenter, randomized, active-controlled study to assess the safety and efficacy of a regimen containing elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS 9350 versus Atripla 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: Fixed-dose combination tablet of elvitegravir (EVG) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg/GS 9350 150 mg QD + Placebo for Atripla QHS (n = 50)

Treatment Arm 2: Atripla QHS + Placebo for fixed-dose combination tablet of elvitegravir (EVG) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg/GS 9350 150 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 the EVG/FTC/TDF/GS 9350 fixed-dose combination tablet until it becomes 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 transmaninases 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/uL
Serum amylase less than or equal to 1.5 x ULN
Normal TSH
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
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 or NNRTIs or primary PI resistance mutation(s)
Hepatitis B surface Antigen 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 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 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: NCT00869557

Show 46 Study Locations

Sponsors and Collaborators

Gilead Sciences

More Information

Additional Information:

Gilead Sciences This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00869557 History of Changes
Other Study ID Numbers:	GS-US-236-0104
Study First Received:	March 24, 2009
Last Updated:	October 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

HIV
HIV 1
Antiretroviral Treatment-Naive
treatment naive

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir disoproxil
Tenofovir

Efavirenz
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 09, 2012