E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10061461 |
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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 |
The primary objective of this study will be to assess the efficacy of combined therapy with Tadalafil and Testosterone to improve the erectile function of ED patients with low or low normal levels of testosterone that do not respond to Tadalafil alone. For that the administration of testosterone will be randomized, double blind, and placebo controlled while administration of Tadalafil will be performed open labeled.
The primary efficacy variable will be the mean change from baseline in the Erectile Function Domain Score of the IIEF (questions 1-5 + 15) on Tadalafil + Testosterone compared to the one on Tadalafil + placebo.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to confirm the beneficial effects of combining testosterone with Tadalafil in the ED patients non-responders to Tadalafil alone by comparing the 2 groups of patients (on Tadalafil + testosterone and on Tadalafil + placebo) as concerns the following parameters at the different times of the study : - rate of “responders” to treatment, defined as the patients having attained a score of 4 or 5 at both Q3 AND Q4 of the IIEF - rate of the patients having achieved a score > 26 at the EFD of the IIEF (considered to define normal erectile function) - mean scores obtained at Questions 3 and 4 of the IIEF - mean scores obtained at the 4 other domains of the IIEF (Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction Domains), as well as at the whole IIEF (sum of the 15 questions). - percentage of “YES” responses at questions 2, 3, 4 and 5 of the Sexual Encounter Profile (SEP)
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. ED complaint ongoing for over 3 months; 2. Age comprise between 45 and 80 y.o.; 3. Had a stable heterosexual relationship for more than 3 months and anticipates having the same partner for all the study 4. Has not responded adequately to the highest available dosage of Tadalafil or other PDE5 inhibitors (20 mg for Tadalafil and Vardenafil, 100 mg for Sildenafil) taken at least at 4 separate occasions, defined as: - a score of 2,3 or 4 at Question n°3 of the IIEF AND - a score of 2 or 3 at Question n°4 of the IIEF; measured prior to Visit 1 5. Low or low-to-normal serum testosterone level (either on total or bioavailable testosterone levels) with respect to the range of men under aged than 50 y.o. (TT < 4 ng/ml and/or BT < 1 ng/ml) according to a first assay done prior to Visit 1 and a confirmation by a second assay at central laboratory Biolille on blood sampled at Visit 1 6. Agrees to make at least 4 attempts at sexual intercourse on 4 separate days during the 4 weeks run-in period with daily Tadalafil 10 mg 7. At least 50% of attempts during this period must be unsuccessful according an answer “No” at one of the questions 1 (“were you able to achieve at least some erection (some enlargement of the penis)?”), 2 (“were you able to insert your penis in your partner’s vagina?”) or 3 (“did your erection last long enough for you to have successful intercourse?”). 8. At the end of the run in phase with Tadalafil 10 mg daily, the patient should provide: - a score of 2, 3 or 4 at Question n°3 of the IIEF AND - a score of 2, 3 at Question n°4 of the IIEF
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E.4 | Principal exclusion criteria |
1. Impotence caused by other primary sexual disorder (e.g. premature ejaculation); 2. History of penile implant or significant penile deformity; 3. Body mass index >35kg/m2; 4. Diabetes mellitus that is uncontrolled (HbA1c level > 10%). HbA1c will be checked at screening for each diabetic patient or suspected to be; 5. Uncontrolled thyroid disorders; 6. Known hyperprolactinemia (serum prolactin > 30ng/ml in local laboratory); 7. Organic hypothalamic-pituitary pathology; 8. History of alcohol, drug or substance abuse within 6 months before Visit 1; 9. Renal insufficiency defined as receiving renal dialysis, having a creatinine clearance < 30 ml/mn, or serum creatinine > 30 mg/ml; 10. Severe hepatic impairment, Child Pugh class C, elevation of AST and/or ALT > 3 x the ULN; 11. Systolic Blood Pressure > 170 or < 90 mm Hg or diastolic blood pressure > 110 or < 50 mm Hg at screening; 12. Cardiac disease contra-indicating any sexual activity; 13. Unstable angina within 6 months before Visit 1; 14. Angina during sexual intercourse within 6 months before Visit 1; 15. Myocardial Infarction within 90 days before Visit 1; 16. Coronary artery by-pass graft surgery or percutaneous coronary intervention (angioplasty or stent insert) within 90 days before Visit 1; 17. Severe cardiac rhythm disturbances e.g. supraventricular arrhythmia with a ventricular response >100 bpm. at rest despite medical or device therapy, history of refractory spontaneous or induced sustained ventricular tachycardia (heart rate > 100 bpm. for > 30 sec) or fibrillation, automatic internal cardioverter-defibrillator, history of sudden cardiac arrest) within 6 months before Visit 1;
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable in the study will be based on the average change from baseline in the Erectile Function Domain Score of the IIEF (question 1-5 +15, possible total score 1 to 30). |
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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 | No |
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 | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 13 |