A Phase IV, Randomized, Double-Blind, Placebo-Controlled Two-Phase Crossover Study of the Metabolic Impact of Tenofovir Disoproxil Fumarate on HIV 1 Seronegative Healthy Adult Males

• Conditions: Human Immunodeficiency Virus (HIV-1) infection; MedDRA version: 7.0Level: PTClassification code 10020161

• Registration Number: EUCTR2004-005083-25-GB
• Lead Sponsor: Gilead Sciences Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-03-22
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

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

Inclusion Criteria

• Subjects must have documented negative HIV serology by ELISA and P24 antigen. This will be done at the screening visit.

• Subjects must be clinically well males aged between 18 to 55 years.

• Adequate renal function (calculated creatinine clearance (CrCl) = 100 mL/min)

• Fasting blood glucose, total cholesterol and triglycerides within normal limits

• Hepatic transaminases (AST and ALT) = 3 x upper limit of normal (ULN)

• Total bilirubin = 1.5 mg/dL

• Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets = 50,000/mm3; hemoglobin =8.0 g/dL)

• Serum amylase = 1.5 x ULN (subjects with serum amylase > 1.5 x ULN will remain eligible if pancreatic lipase is less than or equal to 1.5 x ULN)

• Serum phosphorus = 2.2 mg/dL

• Sexually active males must use condoms

• 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 with a waist hip ratio > 0.97 or BMI > 28 kg/m2 will be excluded

• Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit)

• Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit)

• Other metabolic syndrome or disease process likely to cause marked disturbance in glucose and lipid homeostasis

• Receiving on-going therapy with any of the following:
• Metabolically active medications
• Any lipid-lowering medication
• Hormonal agents (oestrogens or androgens)
• Glucocorticoids
• Beta-blockers
• Thiazide diuretics
• Thyroid preparations
• Psychotropic agents
• Anabolic steroids
• Megoestrol acetate
• Nephrotoxic agents
• aminoglycoside antibiotics
• IV amphotericin B
• cidofovir
• cisplatin
• foscarnet
• IV pentamidine
• other agents with significant nephrotoxic potential
• Vancomycin
• Oral or IV ganciclovir
• Agents that inhibit or compete for elimination via active renal tubular secretion
• Probenecid
• Systemic chemotherapeutic agents (i.e., cancer treatment medications)
• Systemic corticosteroids
• Interleukin 2 (IL 2) and other immunomodulating agents
• Investigational agents
Administration of any of the above medications must be discontinued at least 30 days prior to the baseline visit and for the duration of the study period.

• Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.

• Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance.

• Malignancy or basal cell carcinoma.

• Active, serious infections requiring parenteral antibiotic therapy within 15 days prior to screening.

• Prior history of significant renal or bone disease.

• Subjects should avoid giving blood for the duration of this 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.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the impact on insulin sensitivity (determined by peripheral glucose uptake using a euglycaemic clamp) of the administration of tenofovir DF compared with placebo for two weeks in HIV 1 seronegative healthy male volunteers.;Secondary Objective: • To assess endothelial function by monitoring changes in flow-mediated arterial dilatation and Selectin P/E and PAI 1 assays.<br><br>• To monitor adipocytokines by assessing adiponectin and leptin levels.<br><br>• To monitor lipids by assessing large and small lipoprotein sub fractions of HDL and LDL cholesterol, triglycerides, and non-esterified fatty acid concentrations.<br><br>• To assess the effects on mitochondrial DNA content in peripheral blood mononuclear cells.<br>;Primary end point(s): The primary efficacy endpoint of this study is insulin-mediated glucose disposal during a hyperinsulinaemic euglycaemic clamp study.