E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Many endothelin receptor antagonists have profound effects on the histology and function of the testes in animals. These drugs have been shown to induce atrophy of the seminiferous tubules of the testes and to reduce sperm counts and male fertility in rats when administered for longer than 10 weeks. Where studied, testicular tubular atrophy and decreases in male fertility observed with endothelin receptor antagonists appear irreversible.
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effects of chronic TRACLEER treatment on testicular function via semen analysis in male patients with idiopathic pulmonary arterial hypertension (iPAH) or PAH related to congenital heart disease (CHD) |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male patients age 18-65 years,
2. Bosentan-naïve,
3. WHO functional class III/IV, in need of TRACLEER,
4. Patients with iPAH or PAH secondary to CHD,
5. Written informed consent. |
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E.4 | Principal exclusion criteria |
1. Female,
2. Patients with PAH secondary to connective tissue vascular diseases or HIV,
3. Patients who have undergone a vasectomy,
4. Patients with a sperm concentration < 20 x 10[6]/mL at the first or second baseline visit,
5. Patients with average baseline sperm motility <20% or normal sperm morphology <5%,
6. Body weight < 50 kg,
7. Hypotension, defined as systolic blood pressure less than 85 mm Hg,
8. AST and/or ALT plasma levels greater than 3 times ULN,
9. Hypersensitivity to bosentan or any of the components of the formulation,
10. Treatment with glyburide, calcineurin inhibitors (e.g., cyclosporine A, tacrolimus) or fluconazole at inclusion or planned during the study,
11. Treatment with hormone suppressive agents, including androgens, estrogens, anabolic steroids or glucocorticoids within the past 6 months or planned during the study,
12. Current treatment less than 3 months prior to inclusion or planned new treatment with prostacylin or prostacyclin analogues (e.g., Flolan or Remodulin),
13. Patients receiving spironolactone (aldactone) less than 3 months prior to inclusion or dose >25 mg/day at baseline or anytime during the study,
14. Patients who received an investigational drug in the month preceding the study start or who are due to be treated with another investigational drug during the study period,
15. Known drug or alcohol dependence or any other factors that will interfere with conduct of the study,
16. Any illness other than PAH that will reduce life expectancy to less than 6 months,
17. Active cancer,
18. Prior treatment with an anti-neoplastic agent or ionizing radiation,
19. Hot tub/Jacuzzi use,
20. Uncontrolled diseases including diabetes, liver or kidney disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the proportion of patients with a mean decrease in sperm concentration to 7.5 x 10[6]/mL or below, without a single sperm concentration >= 20 x 10[6]/mL, at 3 or 6 months. This proportion is considered of clinical relevance if greater than 30%. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |