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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
United States, Colorado
The Children's Hospital - Site 9102
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center - Site 9104
Washington, District of Columbia, United States, 20010
United States, New York
Columbia University Medical Center Children's Hospital of New York Presbyterian - Site 9101
New York, New York, United States, 10032
United States, Texas
Texas Children's Hospital - Department of Cardiology - Site 9107
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital - Site 9106
Seattle, Washington, United States, 98105
Australia
Royal Children's Hospital Melbourne, Cardiology - Site 5001
Parkville, Australia, 3052
Belarus
The Republican Scientific-Practical Center "Cardiology" - Site 3001
Minsk, Belarus, 220036
China
Cardiovascular Institute and Fuwai Hospital
Beijing, China, 100037
Beijing Anzhen Hospital, Capital Medical University- Department of Pediatric Cardiology - Site 5103
Beijing, China, 100029
West China 2nd university Hospital-Center of interventional diagnosis and therapy for Children's cardiovascular disease - Site 5104
Chengdu, China, 610041
Guangdong General Hospital - Site 5105
Guangdong, China, 510080
Shanghai Children's Medical Center - Site 5102
Shanghai, China, 200127
Shanghai Pulmonary Hospital, Department of Pulmonary Circulation - Site 5101
Shanghai, China, 200433
Czech Republic
Fakultní nemocnice v Motole, dětské kardiocentrum - Site 3301
Prague, Czech Republic, 150 06
France
Hopital Necker-Enfants Malades, Service de Cardiologie Pédiatrique - Site 2201
Paris, France, 75743
CHU de Toulouse - Hôpital des Enfants, Service de Cardiologie Pédiatrique - Site 2202
Toulouse, France, 31059
Germany
Deutsches Herzzentrum Kinderkardiologie - Site 1401
Berlin, Germany, 13353
Universitätsklinikum Bonn Abteilung für Kinderkardiologie - Site 1404
Bonn, Germany, 53113
Justus-Liebig-Universität Giessen, Kinderherzzentrum - Site 1403
Giessen, Germany, 35392
Hungary
Gottsegen György Országos Kardiológiai Intézet, Gyermekszív Központ, Gyermek Kardiológiai osztály - Site 3401
Budapest, Hungary, 1096
Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Gyermekgyógyászati Klinika és Gyermekegészségügyi Központ - Site 3402
Szeged, Hungary, 6720
India
CARE Hospitals, Cardiology Dep. Hyderabad - Site 5302
Hyderabad, India, 500001
Indraprashta Apollo Hospitals, Pediatric Cardiology - Site 5303
New Dehli, India, 110076
Israel
Schneider Children's Medical Center- Institute of pediatric cardiology - Site 7101
Petach Tikvah, Israel, 49202
Italy
Università Degli Studi di Padova - Dipartimento di Pediatria - Servizio di Cardiologia Pediatrica - Site 1501
Padova, Italy, 35128
Ospedale Pediatrico "Bambino Gesù" - Dipartimento Medico Chirurgico di Cardiologia Pediatrica - Site 1502
Rome, Italy, 00193
Mexico
Instituto Nacional de Cardiologia (INC) Ignacio Chavez - Site 8401
Mexico City, Mexico, 14080
Unidad de Investigacion Clinica en Medicina, SC (UDICEM) - Site 8402
Monterrey, Mexico, 64710
Netherlands
Universitair Medish Centrum Groningen, Kindercardiologie - Site 1601
Groningen, Netherlands, 9713 GZ
Poland
Uniwersyteckie Centrum Kliniczne Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca - Site 3604
Gdansk, Poland, 80-952
Instytut Centrum Zdrowia Matki Polki Klinika Kardiologii ICMP w Lodz - Site 3602
Lodz, Poland, 93-336
Instytut Pomnik - Centrum Zdrowia Dziecka Klinika Kardiologii Dziecięcej - Site 3601
Warszawa, Poland, 04-730
Wojewódzki Szpital Specjalistyczny we Wrocławiu Oddział Kardiologii Dziecięcej z pododdziałem Intensywnego Nadzoru Kardiologicznego - Site 3605
Wroclaw, Poland, 51-124
Russian Federation
RAMS Institution, Research Institute for complex issues of cardiovascular diseases, Siberian branch of the Russian Academy of Medical Sciences - Site 3805
Kemerovo, Russian Federation, 650002
Moscow Scientific Research Institute for Pediatrics and Childrens Surgery of Rosmedtechnologies - Site 3804
Moscow, Russian Federation, 125412
Scientific Center of Cardiovascular Surgery named after A.N.Bakulev of the RAMS - Site 3803
Moscow, Russian Federation, 121552
Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies" - Site 3802
St. Petersberg, Russian Federation, 197341
State Educational Institution of Higher Professional Education "Saint Petersburg State Pediatric Medical Academy of Roszdrav" - Site 3801
St. Petersburg, Russian Federation, 194100
Serbia
Univerzitetska dečja klinika, Služba za kardiologiju - Site 3901
Belgrade, Serbia, 11000
Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Služba za ispitivanje i lečenje bolesti srca i krvnih sudova - Site 3902
Belgrade, Serbia, 11070
South Africa
Department of Paediatric Cardiology University of the Free State - Site 6001
Bloemfontein, South Africa, 9300
Paediatric Cardiology Albert Luthuli Central Hospital - Site 6003
Durban, South Africa, 4001
Division of Paediatric Cardiology, Steve Biko Academic Hospital - Site 6002
Pretoria, South Africa, 0001
Spain
Hospital Universitatario Vall d'Hebron, Neumologia - Site 1907
Barcelona, Spain, 08035
Hospital Universitario La Paz - Paediatric Cardiology Department - Site 1906
Madrid, Spain, 28046
Ukraine
Clinical Diagnostic Center - Pediatric Cardiovascular and ANES and Intensive Care Department - Site 4103
Dnepropetrovsk, Ukraine, 49060
Gusak Ins Urgent and Recovery SUR AMS - Cardiovascular Rehabilitation Pediatric Department - Site 4101
Donetsk, Ukraine, 83045
Gover INS - Scientific Practical Cardiovascular Pediatric Center - MOH Ukraine - Site 4102
Kiev, Ukraine, 01135
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 July 29, 2014