Pulmonary Arterial Hypertension in Children - Full Text View

Purpose

The AC-052-373 study is a PK phase III study to compare two dosing regimen of the pediatric bosentan formulation as well as efficacy and safety in children with Pulmonary Arterial Hypertension (PAH) <12 years of age.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: bosentan	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Bosentan

U.S. FDA Resources

Further study details as provided by Actelion:

Primary Outcome Measures:

Daily exposure to bosentan (AUC over 24 hours) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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 (AUCτ), 3 × AUCτ and 2 × AUCτ for three times and two times daily dosing, respectively.

Enrollment:	64
Study Start Date:	January 2011
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 2 bosentan 2 mg/kg t.i.d.	Drug: bosentan bosentan 2mg/kg t.i.d.
Experimental: Arm 1 bosentan 2mg/kg b.i.d.	Drug: bosentan bosentan 2mg/kg b.i.d.

Eligibility

Ages Eligible for Study:	3 Months to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

PAH diagnosis confirmed with right heart catheterization (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)
WHO functional Class I, II or III
Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)
Body weight ≥3,5 kg
Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)
Baseline PAH-therapy (Calcium channel blocker, bosentan, prostanoid, 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
Signed informed consent by the parents or legal representatives

Exclusion Criteria:

PAH etiologies other than listed above
Non-stable disease status
Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
Systolic blood pressure < 80% of the lower limit of normal range
AST and/or ALT values > 1.5 times the upper limit of normal range.
Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.
Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet
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
Treatment with another investigational drug within 1 month prior to randomization or planned treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01223352

Show 48 Study Locations

Sponsors and Collaborators

Actelion

More Information

No publications provided

Responsible Party:	Actelion
ClinicalTrials.gov Identifier:	NCT01223352 History of Changes
Other Study ID Numbers:	AC-052-373
Study First Received:	October 12, 2010
Last Updated:	March 27, 2013
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: Human Research Ethics Committee Belarus: Ministry of Health Belarus: Local Ethics Committee China: Ethics Committee China: Food and Drug Administration Czech Republic: Ethics Committee Czech Republic: State Institute for Drug Control France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé France: Institutional Ethical Committee France: Conseil National de l'Ordre des Médecins Germany: Ethics Commission Germany: Federal Institute for Drugs and Medical Devices Hungary: Institutional Ethics Committee Hungary: National Institute of Pharmacy India: Drugs Controller General of India India: Institutional Review Board Israel: Ethics Commission Israel: Ministry of Health Italy: Ethics Committee Italy: The Italian Medicines Agency Mexico: Ethics Committee Mexico: Federal Commission for Protection Against Health Risks Netherlands: Medical Ethics Review Committee (METC) Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Ethics Committee Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Russia: Ethics Committee Russia: FSI Scientific Center of Expertise of Medical Application Russia: Ministry of Health of the Russian Federation Russia: Pharmacological Committee, Ministry of Health Serbia: Medicines and Medical Devices Agency of Serbia Serbia: Ethics Committee South Africa: Human Research Ethics Committee South Africa: Medicines Control Council Spain: Agencia Española de Medicamentos y Productos Sanitarios Spain: Ethics Committee Ukraine: State Pharmacological Center - Ministry of Health Ukraine: Ethics Committee United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Actelion:

bosentan
pulmonary arterial hypertension
pediatric

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013

Pulmonary Arterial Hypertension in Children (FUTURE 3)