Male hypogonadism is generally characterised by abnormally low serum testosterone levels. Symptoms include changes in mood, decreased bone mineral density, increased body fat, decreased muscle mass and strength and sexual dysfunction. A number of conditions can also be associated with decreased testosterone production including metabolic syndrome, type II diabetes mellitus, atherosclerosis, myocardial infarction and chronic heart failure
Conditions
Interventions
Trade Name: Tostrex 2% Gel
Product Name: Tostrex
Pharmaceutical Form: Gel
INN or Proposed INN: Testosterone
CAS Number: 58-22-0
Sponsors
Prostrakan Pharmaceuticals Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male patients aged at least 40 years old 2. An early morning total testosterone level less than or equal to 11 nmol/L or calculated free testosterone levels less than or equal to 255 pmol/L, at least two separate timepoints, (between 08.00 - 10.00), at least one week apart. 3. At least two symptoms of hypogonadism (e.g. decreased libido, erectile function, lean body mass or muscle mass; decrease in bone mineral density resulting in osteoporosis; depression, irritability and diminution of mental acuity; fatigue; and vasomotor symptoms, such as hot flushes) 4. Metabolic syndrome as defined by the International Diabetes Federation (IDF): Central obesity (defined as a waist circumference greater than or equal to 94 cm for Europid men, with ethnicity specific values for other groups) and any two of the following four factors: (a) raised TG level: greater than or equal to 150 mg/dL (greater than or equal to 1.7 mmol/L), or specific treatment for this lipid abnormality (b) reduced HDL cholesterol: less than 40 mg/dL (less than 1.03 mmol/L in males, or specific treatment for this lipid abnormality (c) raised blood pressure: systolic BP greater than or equal to 130 mmHg or diastolic BP greater than or equal to 85 mmHg, or treatment of previously diagnosed hypertension (d) raised fasting plasma glucose (FPG) greater than or equal to 100 mg/dL (greater than or equal to 5.6 mmol/L), or previously diagnosed type 2 diabetes mellitus. If above 100 mg/dL or 5.6 mmol/L, an oral glucose tolerance test (OGTT) is strongly recommended but is not necessary to define presence of the syndrome. and/or type 2 diabetes mellitus as defined by: fasting plasma glucose (FPG) greater than or equal to 126 mg/dL (greater than or equal to 7.0 mmol/L) on two occasions or random glucose greater than or equal to 200 mg/dL (greater than or equal to 11.1 mmol/L) and classic symptoms of type 2 diabetes mellitus (polyuria, polydipsia, polyphagia, with / without weight loss) or previously diagnosed type 2 diabetes mellitus. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Treatment with testosterone replacement therapy within 6 months of randomisation 2. Use of any other hormone manipulating therapy, or glucocorticoids and topical steroids (intranasal, inhaled or dermal) within 3 months of randomisation 3. Insulin treated patients 4. History of, or current prostate carcinoma 5. Age-adjusted elevated PSA level 6. Abnormal DRE of prostate, suggestive of cancer 7. Severe symptomatic benign prostatic hyperplasia 8. Patients actively or potentially trying to start a family or requiring fertility treatment 9. Clinically significant hepatic, respiratory, haematological (haematocrit not greater than 52% at Baseline) or renal disease 10. History of drug or alcohol abuse 11. Receiving other trial drugs within 12 weeks 12. Symptomatic obstructive sleep apnoea syndrome 13. History or presence of male breast cancer 14. Hyperprolactinaemia or pituitary tumour 15. Any other reason, which the Investigator feels precludes safe inclusion of the patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to determine the effect of Tostrex® 2% gel on insulin resistance in hypogonadal patients with metabolic syndrome and/or type 2 diabetes mellitus after both 6 months and 2 years of testosterone replacement therapy (TRT).; Secondary Objective: To assess the effect of Tostrex® 2% gel on change in abdominal obesity, lipid profile, glycaemic control and insulin sensitivity after 6 months and 2 years of treatment. To assess the effect of Tostrex® 2% gel on the change in symptoms of hypogonadism after 6 months and 2 years of treatment. To assess the effect of Tostrex® 2% gel in each disease specific subgroup of patients (i.e. metabolic syndrome or type 2 diabetes mellitus), on the change in abdominal obesity, lipid profile, glycaemic control and insulin sensitivity after 6 months and 2 years of treatment. To assess the effect of Tostrex® 2% gel on the change in Framingham Cardiovascular Risk Score and the number of cardiovascular events after 2 years of treatment. To identify change in LV long axis function with testosterone replacement therapy in a subgroup of hypogonadal males with metabolic syndrome and/or type 2 diabetes mellitus. To assess the safety and tolerability of Tostrex® 2% gel compared to placebo gel. ; Primary end point(s): The primary efficacy variable of this study is the change in insulin resistance as assessed by an ITT analysis at 6 months and 2 years as measured by the HOMA-IR. The secondary efficacy variables of this study are: 1. Change in abdominal obesity as measured by changes in waist-hip ratio, percentage body fat, percentage lean mass, BMI and circumference of the waist from Baseline 2. Change in lipid profile from Baseline 3. Change in glycaemic control and insulin sensitivity as assessed by changes in | — |
Countries
Belgium, Germany, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed