Bosentan in Children With Pulmonary Arterial Hypertension Extension Study

Pulmonary Arterial Hypertension Clinical Trial

— FUTURE 2  

Official title:

An Open Label, Long-term, Safety, and Tolerability Extension Study Using the Pediatric Formulation of Bosentan in the Treatment of Children With Idiopathic or Familial Pulmonary Arterial Hypertension Who Completed FUTURE 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319020
• Other study ID #: AC-052-367
• Secondary ID: 2005-001967-70
• Status: Completed
• Phase: Phase 3
• First received: April 26, 2006
• Last updated: June 2, 2016
• Start date: August 2005
• Est. completion date: October 2011

Study information

• Verified date: June 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: SwissmedicUnited States: Food and Drug AdministrationNetherlands: Medicines Evaluation BoardGermany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The main objective of the FUTURE-2 study was to assess the long-term safety and tolerability of the pediatric formulation of bosentan in children with idiopathic pulmonary arterial hypertension or familial pulmonary arterial hypertension who completed FUTURE-1 study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 11 Years

Eligibility

Inclusion Criteria:

• Signed informed consent by the parents or the legal representatives.

• Patients who completed the FUTURE 1 study.

• Patients who tolerated bosentan pediatric formulation and for whom bosentan is considered beneficial at the end of FUTURE 1.

• Males or females >= 2 and < 12 years of age at enrollment in FUTURE 2 (this study). Females who are menstruating must have a negative pregnancy test. A reliable method of contraception must be considered, if appropriate.

Exclusion Criteria:

• Intolerance to bosentan despite dose reductions.

• Any clinically significant laboratory abnormality that precludes continuation of bosentan therapy.

• Pregnancy or breast-feeding.

• Known hypersensitivity to bosentan or any of the excipients.

• Premature and permanent study drug discontinuation during FUTURE 1.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Bosentan
32-mg dispersible and breakable tablet. The body weight-adjusted dose of the dispersible tablet was dispersed in a teaspoon of water (not mixed with food) before being administered orally

Locations

Country	Name	City	State
France	Hopital Antoine Beclere	Clamart
France	Hopital Necker	Paris
France	CHE de Toulouse Hopital d'Enfants	Toulouse
Germany	Deutsches Herzzentrum	Augustenburger
Germany	Universitats Kinderklinik	Giessen
Italy	Policlinico S. Orsola-Malpighi	Bologna
Netherlands	Beatrix Children's Hospital	Groningen
Switzerland	Hopital des Enfants	Geneva
United Kingdom	The Institute of Child Health	London
United States	The Children's Hospital Cardiac Care Center	Denver	Colorado
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Switzerland,  United Kingdom, 

References & Publications (1)

Berger RM, Haworth SG, Bonnet D, Dulac Y, Fraisse A, Galiè N, Ivy DD, Jaïs X, Miera O, Rosenzweig EB, Efficace M, Kusic-Pajic A, Beghetti M. FUTURE-2: Results from an open-label, long-term safety and tolerability extension study using the pediatric FormUl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to end of study (EOS) in systolic blood pressure (SBP)	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure.	From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation)	Yes
Primary	Change from baseline to end of study (EOS) in diastolic blood pressure (DBP)	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure.	From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation)	Yes
Primary	Change from baseline to end of study (EOS) in pulse rate	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in pulse rate.	From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation)	Yes
Primary	Change from baseline to end of study (EOS) in body weight	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including growth as measured by changes from baseline in body weight and height.	From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation)	Yes
Primary	Change from baseline to end of study (EOS) in height for age.	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including growth as measured by changes from baseline in body weight and height.; For each patient, height was put in the perspective of the height of healthy children of the same age according to the WHO growth standards.	From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation)	Yes
Primary	Proportion of patients with treatment-emergent liver function abnormalities	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including laboratory abnormalities related to liver enzymes.; Proportion of patients with increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above 3 x ULN (upper limit of normal) is reported here.	After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2	Yes
Primary	Proportion of patients with treatment-emergent hemoglobin abnormalities	The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including hemoglobin abnormalities.; Proportion of patients with marked hemoglobin decreases (i.e., decrease of or above 15% of the lower normal limit (LL)) is reported here.	After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2	Yes
Primary	Number of subjects with adverse events leading to premature discontinuation of study treatment		From the first study drug administration in FUTURE 1	Yes