Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers
Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Tenofovir Disoproxil Fumarate (Drug); Tenofovir DF placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Gilead Sciences Official(s) and/or principal investigator(s): Graeme Moyle, MD, MB, BS, DipGUM, Principal Investigator, Affiliation: Chelsea and Westminster Hospital, London, UK
Summary
Metabolic changes commonly occur in HIV therapy. The purpose of this study is to assess the
impact on insulin sensitivity from the administration of tenofovir disoproxil fumarate 300
mg compared with placebo in non-HIV-1 infected healthy adult males. Additionally,
endothelial function, adipocytokines and lipids will be monitored.
Clinical Details
Official 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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: 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: To assess endothelial function by monitoring changes in Selectin P/E and PAI-1 assays.To monitor adipocytokines by assessing adiponectin and leptin levels. To monitor lipids by assessing large and small lipoprotein sub-fractions of HDL and LDL cholesterol, triglycerides, and non esterified fatty acid concentrations.
Detailed description:
Double-blind, randomized, placebo-controlled study using a two-sequence two-period crossover
structure. Sixteen HIV-1-negative males will be randomized 1: 1 to one of two treatment
arms.
Group 1:
- Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14
days of the study.
- Tenofovir DF placebo tablet QD for the last 14 days of the study.
Group 2:
- Tenofovir DF placebo tablet QD for the first 14 days of the study.
- Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14
days of the study.
Physical examinations and laboratory analyses are conducted at screening, baseline, Day 14,
and Day 28. A euglycaemic clamp protocol and an ECG are performed at the baseline, Day 14
and Day 28 visits.
The primary efficacy endpoint of this study is insulin-mediated glucose disposal during a
hyperinsulinaemic euglycaemic clamp study. Endothelial function will be monitored by
Selectin P/E and PAI-1 levels; adipocytokine levels will be monitored by measuring
adiponectin and leptin levels; and lipid subfractions, including cholesterol (large and
small subfractions of HDL and LDL) triglycerides and non-esterified fatty acids will be
measured. Safety will be evaluated by adverse event and clinical laboratory test reporting.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Male.
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.
Locations and Contacts
Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom
Additional Information
Starting date: July 2006
Last updated: March 31, 2008
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