E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The metabolic syndrome constitutes a cluster of risk factors for cardiovascular disease with increased morbidity and mortality. The metabolic syndrome is referred to as a concomitant occurrence of hypertension, hyperlipidemia, impaired glucose tolerance with insulin resistance and abdominal obesity.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052066 |
E.1.2 | Term | Metabolic syndrome |
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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 evaluate the efficacy of testosterone treatment (1% testosterone hydroalcohol gel) compared to placebo, with respect to insulin resistance together with other circulatory and metabolic variables. |
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E.2.2 | Secondary objectives of the trial |
Glycemic control and oral glucose tolerance and other metabolic variables of importance will also be evaluated, especially blood lipid levels and markers for cholesterol metabolism. will be evaluated by standardized laboratory measurements and visceral abdominal obesity will be assessed by anthropometric assessment and computerised tomography at three different levels of L3-L4 and the liver, the latter to reflect changes in lipid accumulation in the liver (steatosis). Furthermore adiponectin will be assessed. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male 30 to 70 years (inclusive) 2. Metabolic syndrome defined according to the International Diabetes Foundation (IDF): a) Abdominal obesity (waist circumference > 94 cm for European men) and any two of the following criteria b) Triglycerides > 1.7 mmol/L or specific treatment for this c) HDL < 1.03 nmol/L or specific therapy for this d) Systolic blood pressure ≥ 130 mmHg or diastolic BP ≥ 85 mmHg e) Fasting plasma glucose ≥ 5.6 mmol/L (venous glucose ≥ 6.1 mmol/L) or previously diagnosed type 2 diabetes mellitus defined by: Fasting plasma glucose ≥ 7.8 mmol/L on two occasions, or random glucose ≥ 11.1 mmol/L and classic symptoms of type 2 diabetes 3. Impaired glucose tolerance If the definition of the metabolic syndrome, as described above, is fulfilled but fasting plasma glucose ≥ 5.6 mmol/L (fasting venous glucose is < 6.1 mmol/L) the result of an oral glucose tolerance test must be classified as reduced glucose tolerance with a venous blood glucose 7.8 - 11.1 mmol/L or higher 120 min after intake of 75 g of glucose in a water solution (2h OGTT) (www.diabetes.org/main/info/pre-diabetes.jsp) 4. Hypogonadism defined as a S-Testosterone 12 nmol/L taken at 8:00-10:00 a.m. and less than 2 months before inclusion in the study. 5. Screening value of HbA1c <7.5 % 6. Weight below and inclusive 120 kg 7. Body Mass Index (BMI) below and inclusive 35 8. Hematocrit below and inclusive 50% 9. Signed Written informed consent obtained
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E.4 | Principal exclusion criteria |
1. Insulin therapy and treatment with glitazones. 2. Use of androgen therapy or anabolic steroids within 6 months of entry into the study. 3. Known congestive heart failure, progressing angina pectoris or a history of myocardial infarction within the last 12 months. 4. Known untreated pituitary disease. 5. A history of significant renal or liver disease or any malignancy. 6. Any disease requiring long-term use of drugs interfering with androgens; spironolactone, Ketoconazol, corticosteroids, cimetidin, fentiazines, tricyclic antidepressives, anabolic steroids, 5-alfa reductase inhibitors, antiestrogens. 7. Prostate Specific Antigen (PSA) 4 ng/ml. 8. Suspected malignancy after prostata palpation, unless biopsy shows the opposite. 9. Malignant tumour of the mammary gland 10. Ongoing micturition problem severely affecting patient’s daily living at the discretion of the investigators judged by the investigator. 11. Any contraindication for treatment with testosterone 1% hydroalchol gel according to the labelling as well as known or suspected allergy to the specific product used in the study. 12. Contagious blood disease. 13. Known alcohol or drug abuse, or any condition associated with poor compliance. 14. Participation in a clinical study during the last 90 days before start of treatment. 15. Previous enrolment or randomisation in the present study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is a measure of insulin sensitivity and will be assessed by the calculation of insulin sensitivity by an index formula based on a homeostasis model of steady state levels of insulin and glucose in the fasting state (Wallace et al 2004). Of the varieties of methods and models the quantitative insulin-sensitivity check index (QUICKI) has been reported to have higher predictive value in estimating outcome of the golden standard for assessment of insulin sensitivity (hyperinsulinemic euglycemic glucose clamp) (Chen et al 2005). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.6 | Cross over | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Yes |
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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |