Bosentan in Children With Pulmonary Arterial Hypertension Extension Study

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Bosentan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bosentan<br>Bosentan was administered at 4 mg/kg twice daily (b.i.d.) until the end of the study. It could be down-titrated to 2 mg/kg b.i.d. if not well tolerated. | Drug: Bosentan<br>* 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<br>* Other names: Tracleer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Study (EOS) in Height for Age. | In order to compare the growth data with those of healthy children, growth curves are calculated from height data collected throughout the follow-up period. For each patient, height measured at each study visit was converted to a z-score and expressed in standard deviations (SD) from WHO growth standards. The Z-score was calculated according to the following formula: Z-score = (observed value of the study participant - median value of the reference population) / SD value of the reference population | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average | 
| 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), i.e. 32 months in average | 
| 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), i.e. 32 months in average | 
| 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), i.e. 32 months in average | 
| 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), i.e. 32 months in average | 
| 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 times upper limit of normal (ULN) is reported here. | After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average | 
| 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, i.e. 31 months in average | 
| Number of Subjects With Adverse Events Leading to Premature Discontinuation of Study Treatment |  | From the first study drug administration in FUTURE 1, for an average of 31 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bosentan, pulmonary arterial hypertension, children, FUTURE 1