An open label, prospective multicenter study to assess the pharmacokinetics, tolerability, safety and efficacy of the pediatric formulation of bosentan two versus three times a day in children with pulmonary arterial hypertension - FUTURE-3

• Conditions: Pulmonary Arterial Hypertension; MedDRA version: 9.1Level: LLTClassification code 10064908; MedDRA version: 9.1Level: LLTClassification code 10064909; MedDRA version: 9.1Level: LLTClassification code 10064910

• Registration Number: EUCTR2010-021825-11-IT
• Lead Sponsor: Actelion Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-08
• Last Update Posted: 30 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. PAH diagnosis confirmed with RHC: - Idiopathic or heritable PAH, or - Associated PAH persisting after complete repair of a congenital heart defect (PAH has to be persistent for at least 6 months after surgery)
2. WHO functional class I, II or III. 3. Male or female = 3 months and < 12 years of age (maximum age at randomization is 11.5 years).
4. Body weight = 3.5 kg.
5. Peripheral oxygen saturation (SpO2) = 88% (at rest, on room air).
6. Baseline PAH therapy (calcium channel blocker, bosentan, intravenous or inhaled prostanoid, oral PDE-5 inhibitor) if present, has to be stable for at least 3 months prior to screening. During the study, all background treatments should remain stable.
7. Signed informed consent by the parents or legal representatives.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. PAH etiologies other than listed above
2. Non-stable disease status, e.g., history of recurrent (near-) syncope or signs and symptoms of non-compensated right heart failure.
3. Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost.
4. Systolic blood pressure < 80% of the lower limit of normal range.
5. AST and/or ALT values > 1.5 times the upper limit of normal range.
6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
7. Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.
8. Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet.
9. Treatment with forbidden medication within 2 weeks or at least 5 times the half-life prior to randomization, whichever is the longest: - Glibenclamide (glyburide) - Cyclosporin A - Sirolimus - Tacrolimus - Fluconazole - Rifampicin (rifampin) - Ritonavir - Co-administration of CYP2C9 inhibitors (e.g., amiodarone, voriconazole) and moderate/strong CYP3A4 inhibitors (e.g., amprenavir, erythromycin, ketoconazole, diltiazem, itraconazole) - Endothelin receptor antagonists (ERAs) other than bosentan 10. Treatment with another investigational drug within 1 month prior to randomization or planned treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to investigate the pharmacokinetics (PK) of the pediatric formulation of bosentan at doses of 2 mg/kg b.i.d. and 2 mg/kg t.i.d. in children with pulmonary arterial hypertension (PAH) from above or equal to 3 months to below 12 years of age.;Secondary Objective: Additional objectives are to evaluate efficacy, tolerability, and safety of bosentan in children with PAH from above or equal to 3 months to below 12 years of age.;Primary end point(s): Main PK endpoint: • Daily exposure to bosentan, i.e., AUC over a period of 24 h (AUC0-24h), and calculated as a multiple of the exposure over a dosing interval (AUC?), 3 ? AUC? and 2 ? AUC? for three times and two times daily dosing, respectively.