Pulmonary Arterial Hypertension
Conditions
Keywords
bosentan, children, pharmacokinetics, pulmonary arterial hypertension
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.
Interventions
DRUGBosentan
Pediatric oral formulation of bosentan, i.e., 32 mg dispersible and breakable tablets
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent by the parents or the legal representatives. * Males or females \>= 2 and \< 12 years of age. * Idiopathic PAH or familial PAH diagnosed by right heart catheterization (Clinical classification of pulmonary hypertension, Venice 2003). * World Health Organization (WHO) functional class II or III. * Oxygen saturation (SpO2) \>= 88% (at rest, on room air). * 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. * 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. * PAH therapy stable for at least 3 months prior to Screening. * Stable treatment with calcium channel blockers, if any, for at least 3 months prior to Screening. * Patient's PAH condition stable for at least 3 months prior to Screening.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | — |
| 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. |
Outcome results
None listed