E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) infection |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• To assess endothelial function by monitoring changes in flow-mediated arterial dilatation and 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.
• To assess the effects on mitochondrial DNA content in peripheral blood mononuclear cells.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is insulin-mediated glucose disposal during a hyperinsulinaemic euglycaemic clamp study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |