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

Sponsored by:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00648817

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Tenofovir Disoproxil Fumarate Drug: Tenofovir DF placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

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 Measures:

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.

Enrollment:	8
Study Start Date:	July 2006
Study Completion Date:	December 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) Drug: Tenofovir DF placebo Tenofovir DF placebo tablet QD
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 Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) Drug: Tenofovir DF placebo Tenofovir DF placebo tablet QD

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00648817

Locations

United Kingdom
Chelsea and Westminster Hospital
London, United Kingdom, SW10 9NH

Sponsors and Collaborators

Gilead Sciences

Investigators

Principal Investigator:

Graeme Moyle, MD, MB, BS, DipGUM

Chelsea and Westminster Hospital, London, UK

More Information

No publications provided

Study ID Numbers:	GS-US-104-0318, EUDRACT Number: 2004-005083-25
Study First Received:	March 27, 2008
Last Updated:	March 31, 2008
ClinicalTrials.gov Identifier:	NCT00648817 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:

HIV-1
tenofovir DF
HIV-1

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Healthy
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors

Virus Diseases
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions

Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil

ClinicalTrials.gov processed this record on July 02, 2009