A 7-month research project for children aged from 3 months to 11 years with pulmonary arterial hypertension to find out whether bosentan is best tolerated, and most safe and effective when taken two or three times a day

• Conditions: Pulmonary arterial hypertension (PAH) in children; MedDRA version: 14.1Level: LLTClassification code 10064908Term: Associated with (APAH)System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1Level: LLTClassification code 10064909Term: Idiopathic (IPAH)System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1Level: LLTClassification code 10064910Term: Familial (FPAH)System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-03
• Last Update Posted: 21 October 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), or
- PAH-CHD (associated with systemic-to-pulmonary shunts, including Eisenmenger syndrome), with PVR > 8 Wood Units and Qp/Qs < 2

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). (in patients with Eisenmenger syndrome SpO2 = 70%)

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: 64
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

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: 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 = 3 months to < 12 years of age.;Secondary Objective: to evaluate efficacy, tolerability, and safety of bosentan in children with PAH from = 3 months to < 12 years of age.;Primary end point(s): The main PK endpoint is defined as the daily exposure to bosentan, i.e., AUC over a period of 24 h (AUC(0-24h)), and calculated as a multiple of the exposure over a dosing interval (AUCt), 3×AUCt and 2xAUCt for three times and two times daily dosing, respectively.<br><br>;Timepoint(s) of evaluation of this end point: Not applicable

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable