E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic late onset hypogonadism |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021011 |
E.1.2 | Term | Hypogonadism male |
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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 |
Efficacy and safety of NEBIDO in men with symptomatic late onset hypogonadism (SLOH) as characterized in the protocol inclusion criteria:
To assess the change from baseline in lean body mass after 54 weeks of treatment with NEBIDO compared to placebo, measured by dual energy X-ray absorptiometry (DEXA).
Safety parameters • Adverse event • Clinical laboratory evaluations (i.e. FBC, creatinine, glucose, potassium, calcium and HbA1c) vital signs, physical examination findings, and other observations related to safety e.g. DRE and IPSS • Standard laboratory tests for androgen treatment: prostate specific antigen (PSA); hemoglobin; hematocrit, • Laboratory tests for lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol and Triglycerides) and liver function tests (aspartate aminotransferase [AST] and alanine transaminase [ALT])
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E.2.2 | Secondary objectives of the trial |
To assess the: • Change from baseline in total body mass, measured by DEXA • Change from baseline in fat mass, measured by DEXA • Change from baseline in visceral fat mass, measured by DEXA • Change from baseline in bone mineral density, measured by DEXA • Aging Male Symptoms (AMS) rating scale ( Total score) • Aging Male Symptoms (AMS) rating scale (sexual function sub domain) • International Index of Erectile Function- erectile function domain (IIEF-EF) • Change in serum levels of testosterone (central laboratory) • Change in waist circumference Where change from baseline, in the first 4 bullet points above, stands for change from baseline after 54 weeks of treatment with NEBIDO compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men aged 50 and older 2. Symptomatic hypogonadism as defined by i and ii: i. Total testosterone below 12nmol/l ii. Aging males’ symptom score above 36 3. Willing to avoid significant change in the pattern of physical exercise and lifestyle for the duration of the study 4. Willing to voluntarily sign a statement of informed consent to participate in the study
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E.4 | Principal exclusion criteria |
1. Use of androgen therapy or anabolic steroids within 12 months of entry into the study (i.e. screening visit/visit 1) 2. Suspicion or known history of prostate or breast cancer 3. Suspicion or known history of liver tumors 4. Hypersensitivity to the active substances or any of the excipients of NEBIDO e.g. Benzyl benzoate and castor oil. Hypercalcemia accompanying malignant tumors 5. Blood coagulation irregularities presenting an increased risk of bleeding after intramuscular injections 6. Diagnosed sleep apnea 7. Polycythemia 8. Hematocrit level >50% at entry to the study (i.e. screening visit/visit 1) 9. Patients using 5-α-reductase inhibitors such as finasteride or dutasteride should be excluded from the study. 10. Prolactin level >25ng/ml 11. Organic hypothalamic-pituitary pathology 12. Severe psychiatric disease 13. Prostate specific antigen (PSA) level ≥4ng/ml 14. Severe symptomatic benign prostatic hyperplasia (IPSS sum score ≥20) 15. Concurrent use of androgens including dehydroepiandrosterone (DHEA), anabolic steroids, clomipramine, antiandrogens, estrogen, cytochrome P450 inducing medicines (e.g. quinidine, ketoconazole, macrolides), corticotrophins (ACTH) and oxyphenbutazone 16. Body mass index >35kg/m2 17. Uncontrolled thyroid disorders 18. Diabetes mellitus with vascular changes or which is uncontrolled 19. Epilepsy not adequately controlled by treatment 20. Migraine not adequately controlled by treatment 21. Patients requiring or undergoing fertility treatment 22. Any clinically significant chronic disease that might, in the opinion of the investigator, compromise patient’s safety interfere with the evaluations, or preclude completion of the trial (e.g. hemochromatosis, chronic lung disease, chronic malabsorption disease) 23. Known history of alcohol or drug abuse 24. Medical, psychiatric or other conditions that compromise the patient’s ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study. 25. Hypertension which is not adequately controlled on therapy 26. Severe cardiac, hepatic or renal insufficiency 27. Coronary heart disease not stabilized by therapy as assessed by the investigator 28. Metal implants in the body (metal implants in the head will not exclude patients from participation) 29. Concomitant participation in another clinical trial within 1 month of entry into this study (i.e. randomized and has taken study medication).
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the change from baseline in lean body mass after 54 weeks of treatment with NEBIDO compared to placebo, measured by dual energy X-ray absorptiometry (DEXA). |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 12 |