Clinical research study involving an experimental drug named cobicistat(GS-9350, COBI) which is being studied in combination with drugs already approved for the treatment of HIV-1 infection. The purpose of this study is to see if COBI when given in combination with atazanavir and FTC/TDF is safe and effective in reducing levels of HIV-1 in the blood of subjects who are treatment-naïve (those who have not received any antiretroviral medication)

Conditions: Human Immunodeficiency Virus (HIV-1) Infections
MedDRA version: 15.1Level: LLTClassification code 10020192Term: HIV-1System Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2009-016759-22-BE

Lead Sponsor: Gilead Sciences Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 700

Inclusion Criteria

• The ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures
• Plasma HIV-1 RNA levels = 5,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time
• Screening genotype report provided by Gilead Sciences must show sensitivity to FTC, TDF and ATV
• Normal ECG (or if abnormal, determined by the Investigator to be not clinically
significant)
• Adequate renal function:
Estimated glomerular filtration rate = 70 mL/min according to the Cockcroft-Gault
formula
• Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN)
• Total bilirubin = 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets
= 50,000/mm3; hemoglobin = 8.5 g/dL)
• Serum amylase = 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is = 5 × ULN)
• Females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug.
- Female subjects who utilize hormonal contraceptive as one of their birth control
methods must have used the same method for at least three months prior to study
dosing
- Female subjects who have stopped menstruating for = 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the
Central Laboratory reference range
• Male subjects must agree to utilize a highly effective method of
contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from screening throughout the study period and for 30 days following discontinuation of investigational medicinal product
• Age = 18 years
• Life expectancy = 1 year
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 693
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

• A new AIDS-defining condition (excluding CD4 cell count and percentage criteria)diagnosed within the 30 days prior to screening
• Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study.
• Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Have an implanted defibrillator or pacemaker
• Have an ECG PR interval = 220 msec
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and must not be anticipated to require systemic therapy during the study.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.
• Subjects receiving ongoing therapy with any of the following medications, including drugs not to be used with GS-9350, FTC, TDF, ATV, and RTV (refer to the list below for drugs which are disallowed for use with GS-9350); or subjects with any known allergies to the excipients of GS-9350 tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets.
Drug Class Agents Disallowed*
Alpha Adrenergic Receptor AntagonistsAlfuzosin
Analeptics Modafinil
Antibacterials Telithromycin
Anticonvulsants Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antifungals Voriconazole
Antihistamines Astemizole, Terfenadine
Antimycobacterials Rifampin, Rifapentine, Rifabutin
Calcium Channel Blockers Bepridil
Ergot Derivatives Ergotamine, Ergonovine,Dihydroergotamine, Methylergonovine, Ergometrine
GI Motility Agents Cisapride
Herbal St. John’s Wort, Echinaccea
HMG-CoA Reductase InhibitorsSimvastatin, Lovastatin, Cerivastatin
Neuroleptics Pimozide
Sedatives/Hypnotics Midazolam, Triazolam
Systemic Corticosteroids with the exception of short-term (<= 1 week) use of prednisone as a steroid burst All agents, including dexamethasone
*Administration of any of the above medications must be discontinued at least 21 days prior to the Baseline/Day 1 visit and for the duration of the study.

•Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial.
•Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of a regimen containing GS-9350-boosted atazanavir versus ritonavir-boosted atazanavir, each administered with emtricitabine/tenofovir disoproxil fumarate, in HIV-1 infected, antiretroviral treatment-naïve adult subjects as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48.;Secondary Objective: - To evaluate the efficacy, safety and tolerability of the two treatment regimens through 96 weeks of treatment. <br>- To evaluate the durability of the efficacy, safety and tolerability results of the two treatment regimens observed through 192 weeks of<br>treatment;Primary end point(s): Proportion of subjects that achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined by the FDA snapshot analysis.;Timepoint(s) of evaluation of this end point: 48 Weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - To evaluate the efficacy, safety and tolerability of the two treatment regimens through 96 weeks of treatment<br>- To evaluate the durability of the efficacy, safety and tolerability results of the two treatment regimens observed through 192 weeks of treatment;Timepoint(s) of evaluation of this end point: - Weeks 96, 144 and 192<br>- Weeks 48, 96, 144 and 192