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

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ClinicalTrials.gov Identifier: NCT00648817
Recruitment Status : Completed
First Posted : April 1, 2008
Last Update Posted : April 1, 2008
Sponsor:
Information provided by:
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE March 27, 2008
First Posted Date  ICMJE April 1, 2008
Last Update Posted Date April 1, 2008
Study Start Date  ICMJE July 2006
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2008)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2008)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Placebo Comparator: 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.
    Interventions:
    • Drug: Tenofovir Disoproxil Fumarate
    • Drug: Tenofovir DF placebo
  • Active Comparator: 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.
    Interventions:
    • Drug: Tenofovir Disoproxil Fumarate
    • Drug: Tenofovir DF placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2008)
8
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2007
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00648817
Other Study ID Numbers  ICMJE GS-US-104-0318
EUDRACT Number: 2004-005083-25
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Graeme Moyle, MD, MB, BS, DipGUM Chelsea and Westminster Hospital, London, UK
PRS Account Gilead Sciences
Verification Date March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP