Bosentan in Children With Pulmonary Arterial Hypertension
- Registration Number
- NCT00319267
- Lead Sponsor
- Actelion
- Brief Summary
The aim of the study is to demonstrate that the exposure to bosentan in children with idiopathic pulmonary arterial hypertension (PAH) or familial pulmonary arterial hypertension, using a pediatric formulation, is similar to that in adults with PAH and to evaluate the tolerability and safety of a pediatric formulation of bosentan in this patient population.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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Signed informed consent by the parents or the legal representatives.
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Males or females >= 2 and < 12 years of age.
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Idiopathic PAH or familial PAH diagnosed by right heart catheterization (Clinical classification of pulmonary hypertension, Venice 2003).
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World Health Organization (WHO) functional class II or III.
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Oxygen saturation (SpO2) >= 88% (at rest, on room air).
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PAH treatment-naïve patients or patients already treated with either:
- Bosentan monotherapy
- Intravenous epoprostenol monotherapy
- Intravenous or inhaled iloprost monotherapy
- Combination of bosentan and intravenous epoprostenol
- Combination of bosentan and intravenous or inhaled iloprost.
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All patients should start the study drug (bosentan pediatric formulation) at 2 mg/kg twice daily (b.i.d.), whether or not they were previously treated with bosentan.
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PAH therapy stable for at least 3 months prior to Screening.
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Stable treatment with calcium channel blockers, if any, for at least 3 months prior to Screening.
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Patient's PAH condition stable for at least 3 months prior to Screening.
- PAH associated with conditions other than idiopathic or familial PAH.
- Non-stable patients, e.g., history (in the last 3 months prior to Screening) of recurrent syncope, or signs and symptoms of non-compensated right heart failure.
- Need or plan to wean patients from intravenous epoprostenol, or intravenous, or inhaled iloprost.
- Body weight < 4 kg.
- Systolic blood pressure < 80%, the lower limit of normal range, according to age and gender.
- AST and/or ALT values > 3 times the upper limit of normal ranges.
- 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 ranges.
- Pregnancy.
- Known intolerance or hypersensitivity to bosentan or any of the excipients.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Bosentan Bosentan The initial dose of bosentan was 2 mg/kg b.i.d. for 4 weeks. After 4 weeks, the initial dose was up-titrated to the maintenance dose of 4 mg/kg b.i.d. up to the end of the study treatment at Week 12. If the maintenance dose was not well tolerated, the dose could be down-titrated to the initial dose.
- Primary Outcome Measures
Name Time Method Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose AUCt was assessed at steady state (i.e., after at least 2 weeks of treatment with a same dose of the study drug) over 12 hours .
- Secondary Outcome Measures
Name Time Method Time to reach the maximum plasma concentration (tmax) of bosentan and its metabolites At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose Maximum plasma concentration (Cmax) of bosentan and its metabolites At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose Maximum observed plasma concentration for bosentan and its metabolites was directly derived from their respective plasma concentration-time curves.
Area under the plasma concentration-time curve during a dose interval (AUCt) for the metabolites of bosentan At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose AUCt was assessed at steady state (i.e., after at least 2 weeks of treatment with a same dose of the study drug) over 12 hours.
Trial Locations
- Locations (11)
Hopital des Enfants
🇨ðŸ‡Geneva, Switzerland
Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
The Institute of Child Health
🇬🇧London, United Kingdom
Beatrix Children's Hospital
🇳🇱Groningen, Netherlands
Hopital Antoine Beclere
🇫🇷Clamart, France
CHE de Toulouse Hopital d'Enfants
🇫🇷Toulouse, France
Hopital Necker
🇫🇷Paris, France
Columbia University Medical Center
🇺🇸New York, New York, United States
Deutsches Herzzentrum
🇩🇪Augustenburger, Germany
Universitats Kinderklinik
🇩🇪Giessen, Germany
The Children's Hospital Cardiac Care Center
🇺🇸Denver, Colorado, United States