Pulmonary Arterial Hypertension in Children (FUTURE 3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01223352
First received: October 12, 2010
Last updated: October 9, 2013
Last verified: October 2013
  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:


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
Study Completion Date: September 2013
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:

  1. 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)
  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, 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
  7. Signed informed consent by the parents or legal representatives

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
  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: October 9, 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 April 23, 2014