Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00648817
• Date of registration: 27/03/2008
• Prospective Registration: No
• Primary sponsor: Gilead Sciences
• Public title: Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers
• Scientific title: 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
• Date of first enrolment: July 2006
• Target sample size: 8
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00648817
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 4

Countries of recruitment

United Kingdom

Contacts

• Name: Graeme Moyle, MD, MB, BS, DipGUM
• Affiliation: Chelsea and Westminster Hospital, London, UK

Key inclusion & exclusion criteria

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 according to the Cockcroft Gault
formula: Male: [(140 - age in years) x (actual body wt in kg)]/[72 x (serum
creatinine in mg/dL)]= CrCl (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 <= 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

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.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Male

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Tenofovir DF placebo

Drug: Tenofovir Disoproxil Fumarate

Primary Outcome(s)

To assess the impact on insulin sensitivity (determined by peripheral glucose uptake suing a euglycaemic clamp) of the administration of tenofovir DF compared with placebo for two weeks in HIV-1 seronegative healthy male volunteers.

Secondary Outcome(s)

To monitor lipids by assessing large and small lipoprotein sub-fractions of HDL and LDL cholesterol, triglycerides, and non esterified fatty acid concentrations.

To assess endothelial function by monitoring changes in Selectin P/E and PAI-1 assays.

To monitor adipocytokines by assessing adiponectin and leptin levels.

Secondary ID(s)

EUDRACT Number: 2004-005083-25

GS-US-104-0318

Source(s) of Monetary Support

Please refer to primary and secondary sponsors