E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular failure. PAH is a serious complication of many types of connective tissue disease (CTD).
PAH is an important cause of morbidity in patients with connective tissue diseases . Once it is diagnosed, it is difficult to treat and has a very poor prognosis |
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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 bosentan treatment on long-term survival in patients with PAH related to connective tissue disease |
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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 |
· Patients with PAH who have completed their participation in the preceding TRUST study with bosentan.
· Provide written informed consent.
· Female patients must be either postmenopausal or surgically or naturally sterile. Women of childbearing potential must have a negative pre-enrollment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.Reliable methods of contraception are: Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide. Intra-uterine devices. Oral, injectable or implantable contraceptives only in combination with a barrier method. Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception. Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception. |
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E.4 | Principal exclusion criteria |
Eligible patients must meet none of the following exclusion criteria:
· Moderate to severe hepatic impairment i.e., Child-Pugh Class B or C
· Baseline liver aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT), greater than 3 times the upper limit of normal ranges.
· Known hypersensitivity to bosentan or any of the excipients of the formulation.
· Treatment with glibenclamide, any calcineurin inhibitor.
· Pregnancy or breast-feeding
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E.5 End points |
E.5.1 | Primary end point(s) |
EFFICACY ENDPOINTS:
. Time to death, . Time to change of PAH therapy, . Change from baseline to one year and end of study in WHO functional class.
SAFETY / TOLERABILITY ENDPOINTS:
· Adverse events up to 24 hours after study drug discontinuation, · Adverse events leading to premature discontinuation of study drug, . Serious adverse events up to 28 days after study drug discontinuation, · Changes from baseline to end of treatment in vital signs. |
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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 | 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) | 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 | No |
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 | No |
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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The study will end 1 year after the last patient has entered the study |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |