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

NCT00648817 | Completed Phase 4

• 2 other identifiers: GS-US-104-0318EUDRACT Number: 2004-005083-25
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

HIV-1; tenofovir DF

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

Study Arms (2)

Group 1

PLACEBO COMPARATOR

* 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.

Drug: Tenofovir Disoproxil Fumarate; Drug: Tenofovir DF placebo

Group 2

ACTIVE COMPARATOR

* 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.

Drug: Tenofovir Disoproxil Fumarate; Drug: Tenofovir DF placebo

Interventions

Tenofovir Disoproxil Fumarate DRUG

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil)

Group 1; Group 2

Tenofovir DF placebo DRUG

Tenofovir DF placebo tablet QD

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Graeme Moyle, MD, MB, BS, DipGUM

  Chelsea and Westminster Hospital, London, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 1, 2008
• Study Start: July 1, 2006
• Primary Completion: November 1, 2007
• Study Completion: December 1, 2007
• Last Updated: April 1, 2008

Record last verified: 2008-03

Locations

GB (1)