E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic or familial pulmonary arterial hypertension |
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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 assess the long-term safety and tolerability of the pediatric formulation of bosentan in children with IPAH or familial PAH.
The primary endpoint analysis will be the analysis of tolerability and safety endpoints:
· Treatment-emergent adverse events up to 24 hours after permanent discontinuation of study drug.
· Adverse events leading to premature discontinuation of study drug.
· Serious adverse events up to 28 days after permanent discontinuation of study drug.
· Changes from baseline to Study End in vital signs, body weight, and height.
· Treatment-emergent marked laboratory abnormalities. |
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E.2.2 | Secondary objectives of the trial |
Exploratory efficacy endpoints:
· Change from Baseline in FUTURE 1 to Study End or Premature study drug discontinuation (FUTURE 1 or 2) in:
- WHO functional class - Quality of life questionnaire (SF-10 for childrenTM) - Global Clinical Impression scale according to the parents/legal representatives - Global Clinical Impression scale according to the physician
· From Baseline in FUTURE 1, time to worsening of PAH, defined as death or transplantation or hospitalization for PAH worsening.
· From Baseline in FUTURE 1, time to worsening of PAH or initiation of new therapy for PAH or new right heart failure or worsening of right heart failure. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
· Signed informed consent by the parents or the legal representatives.
· Patients who completed the FUTURE 1 study.
· Patients who tolerated bosentan pediatric formulation and for whom bosentan is considered beneficial at the end of FUTURE 1.
· Male or female >= 2 and < 12 years of age at enrollment in FUTURE 2. Females who are menstruating must have a negative pregnancy test. A reliable method of contraception must be considered, if appropriate. |
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E.4 | Principal exclusion criteria |
· Intolerance to bosentan despite dose reductions.
· Any clinically significant laboratory abnormality that precludes continuation of bosentan therapy.
· Pregnancy or breast-feeding.
· Known hypersensitivity to bosentan or any of the excipients.
· Premature and permanent study drug discontinuation during FUTURE 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
In addition to long-term tolerability and safety information, the FUTURE 2 study will provide an opportunity to assess quality of life and functional status of the paediatric population using the new formulation. |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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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As indicated on protocol page 7, Study End: the study will continue until: - The investigator or the patient decides to discontinue the study drug permanently, - The study drug as a pediatric formulation is available on the market in the patient’s country for this indication, - The patient reaches the age of 12 years, - Anytime earlier if the sponsor decides not to pursue the development of the pediatric formulation of bosentan.
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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 | |
E.8.9.1 | In the Member State concerned days | |