A Phase IV, Open-label, Prospective Observational Study to Evaluate Virological Response in Antiretroviral-Experienced HIV-1 infected Subjects Switching to Atripla (efavirenz/emtricitabine/tenofovir DF) on an Empty Stomach - ONCE - Only Nocturnal Combination Evaluatio

• Conditions: Antiretroviral-experienced HIV 1 infected subjects on their first and stable HAART regimen of efavirenz, emtricitabine, and tenofovir DF.; MedDRA version: 9.1Level: LLTClassification code 10020192Term: HIV-1

• Registration Number: EUCTR2007-005769-36-GB
• Lead Sponsor: Gilead Sciences Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Subjects must have documented HIV-1 infection by Roche Amplicor® (Version 1.5
Ultra-sensitive) or equivalent assay – either at screening or previously documented in the patient’s medical record.
• Stable HAART regimen of efavirenz, emtricitabine and tenofovir DF or Truvada and
efavirenz for = 24 weeks prior to Screening. (Subjects can have been previously treated with tenofovir DF, lamivudine, and efavirenz or tenofovir DF, emtricitabine, and efavirenz prior to switching to Truvada and efavirenz. They must have switched in order to simplify his/her HAART regimen and must not have had a treatment interruption prior to the switch).
•Undetectable plasma HIV-1 RNA (< 50 copies/mL) at Screening and =12 weeks prior to Screening).
•=18 years old
•Adequate renal function by:
- Estimated creatinine clearance =60 mL/min according to the Cockcroft Gault formula
•Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN)
•Total bilirubin = 1.5 mg/dL
•Adequate hematologic function (absolute neutrophil count =1,000/mm3; platelets =25,000/mm3; hemoglobin =8.0 g/dL
•Serum amylase = 1.5 x ULN (subjects with serum amylase > 1.5 x ULN will remain eligible if serum lipase is = 1.5 x ULN)
•Negative serum pregnancy test (females of childbearing potential only i.e., not surgically sterile or at least two years post-menopausal)
•Women of childbearing potential (WOCBP) must be willing to use two methods of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drugs in such a manner that the risk of pregnancy is minimized.
•Female subjects who utilize hormone contraceptive as one of their birth control methods must have used the same methods for at least three months prior to study dosing.
•Female subjects who are postmenopausal for less than two years are required to have FSH = 40 mIU/mL. If the FSH is < 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study
•Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continuing for up to 12 weeks after the last dose of study drugs
•Life expectancy =1 year
•The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures

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) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Subjects who have been treated with any ARV other than Truvada, tenofovir DF,
emtricitabine, lamivudine or efavirenz
• Known hypersensitivity or toxicities to emtricitabine (FTC), tenofovir DF (TDF) or
Truvada
• Known hypersensitivity or toxicities to lamivudine (3TC) if the subject initiated HAART with tenofovir DF, lamivudine, and efavirenz
•Known hypersensitivity or toxicities to Sustiva
•Have a history of resistance to any of the study agents at the time of screening (documented presence of resistance mutation(s) as defined by the IAS-USA 2005 Guidelines
•A new AIDS-defining condition diagnosed within the 30 days prior to the Baseline visit.
•Pregnant or lactating or breastfeeding females
•Severe hepatic impairment (> 5 times upper limit of normal as defined by laboratory transaminases) or deemed clinically significant by investigator.
•Any current know clinical or laboratory parameter of GSI grade 4. However asymptomatic grade 4 abnormalities will be permitted at the discretion of the investigator if deemed clinically appropriate (excluding AEs and laboratory parameters mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed insignificant by the investigator must be discussed with the sponsor prior to enrollment.
•Receiving on-going therapy with any of the prohibited medications. Administration of any of the medications must be discontinued at least 30 days prior to the Baseline visit and for the duration of the study period.
•Active, serious infections (other than HIV infection) requiring parenteral antibiotic therapy within 30 days prior to Screening visit.
•Current acute illness or infection (e.g., opportunistic) – including an active AIDS defining condition within the previous six months.
•Hepatitis B co-infection or Hepatitis C co-infection
•Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS with 30 days of Baseline visit and are not anticipated to require systemic therapy during the study.
•Prior history of renal or bone disease deemed significant by the investigator.
•Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied has been stopped for more than 1 month.
•Evidence of alcohol and/or drug or substance abuse that in the judgment of the investigator would likely result in the patient being unreliable in fulfilling the conditions of the protocol.
•History of psychological illness or conditions that in the judgment of the investigator might interfere with the patient’s ability to understand the requirements of the study.
•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 and cause the patient to be unable to complete the study protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate pure virological response rates (defined as subjects who do not have pure virologic failure at HIV-1 RNA threshold of 50 copies/mL) in antiretroviral-experienced subjects receiving Atripla for 48 weeks on an empty stomach.;Secondary Objective: •To assess how closely dosing recommendations are adhered to through the use of a subject-reported questionnaire<br>•To assess change in absolute CD4 cell count<br>•To describe the safety and tolerability through the reporting of adverse events and laboratory abnormalities<br>•To evaluate acceptability by using three subject-reported questionnaires, HAART<br>Intrusiveness Scale (m-HIS), Perceived Ease of Regimen for Condition (PERC), and<br>Preference of Medicine (POM) questionnaires, through 48 weeks.;Primary end point(s): The proportion of subjects who maintain pure virologic response at HIV-1 RNA threshold of 50 copies /mL (PVR50; lack of confirmed HIV-1 RNA level =50 copies/mL) through Week 48.