A Phase 3B, Randomized, Open-label Study to Evaluate the Safety and Efficacy of a Single Tablet Regimen of Emtricitabine/Rilpivirine/Tenofovir Disoproxil FumarateCompared with a Single Tablet Regimen of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults.

Conditions: Human Immunodeficiency Virus (Type 1) Infection
MedDRA version: 12.1Level: LLTClassification code 10020192Term: HIV-1

Registration Number: EUCTR2010-024007-27-PT

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 700

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

•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 = 2,500 copies/mL at screening
•No prior use of any approved or experimental anti-HIV drug for any length of time with the exception of PrEP (pre-exposure prophylaxis).
•No use of Truvada or Viread for pre-exposure prophylaxis (PrEP) within 30 days of screening
•Screening genotype report showing sensitivity to EFV, FTC, TDF, and lack of the RPV mutations K101E/P, E138G/K/Q/R, Y181C/I/V, and H221Y
•Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
•Hepatic transaminases (AST and ALT) = 5 x 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 x ULN (subjects with serum amylase > 5 x ULN will remain eligible if serum lipase is = 5 x ULN)
•Adequate renal function:
Estimated glomerular filtration rate = 50 mL/min according to the Cockcroft Gault formula:
Male: ((140 – age in years) x (wt in kg))/ (72 x (serum creatinine in mg/dL)) = CLcr (mL/min)
Female: ((140 – age in years) x (wt in kg) x 0.85) / (72 x (serum creatinine in mg/dL) = CLcr (mL/min)
•Females of childbearing potential (as defined in Section 7.8.1) 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, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study period and for 12 weeks 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, or serum follicle stimulating hormone level is not within the post-menopausal range must agree to utilize highly effective contraceptive methods
•Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit, throughout the duration of the study and for 12 weeks following discontinuation of investigational medicinal product. A highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or male subjects must be non-heterosexually active, practice sexual abstinence, or be vasectomized.
•Adult (= 18 years) males or non-pregnant females
•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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in (or may be discontinued from) this study:
•A new AIDS defining condition diagnosed within the 30 days prior to screening (refer to Appendix 5)
•Females who are breastfeeding
•Positive serum pregnancy test (female of childbearing potential)
•Proven or suspected acute hepatitis in the 30 days prior to study entry.
•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.)
•Have an implanted defibrillator or pacemaker
•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 or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use as indicated in the table below, including drugs not to be used with FTC, EFV, RPV, TDF, and Atripla (refer to the individual agent’s Prescribing Information); or subjects with known allergies to the excipients of the FTC/RPV/TDF single tablet regimen and/or Atripla tablets.

Drug ClassAgents Disallowed*
Analeptics:Modafinil
Antiarrhythmics:Bepridil
Anticonvulsants:Phenobarbital, carbamazepine, oxcarbazepine, and phenytoin
Antibiotics:Rifabutin, rifampin, rifapentine, telithromycin, troleandomycin
Antibacterials:Telithromycin
Antidiabetics:Pioglitazone, troglitazone
Antifungals:Voriconazole
Antihistamines:Astemizole, Terfenadine
Antimycobacterials:Rifampin, Rifapentine, Rifabutin
Calcium Channel Blockers:Bepridil
GI Motility Agents:Cisapride
Glucocorticoids (systemic):Dexamethasone and other glucocorticoids
Ergot Derivatives:Ergotamine, Ergonovine, Dihydroergotamine, Methylergonovine
Herbal/Natural Supplements:St. John’s Wort, Echinaccea
Progestogens:Megestrol Acetate
Proton Pump Inhibitors:Omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole
Neuroleptics:Pimozide
Sedatives/Hypnotics:Midazolam, Triazolam

*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.
•Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine based therapies).
•Have a history of liver disease, including Gilbert’s Disease.
•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 requiremen