Clinical trial NCT00319267: Bosentan in Children With Pulmonary Arterial Hypertension
Official title: An Open Label, Multicenter Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Pediatric Formulation of Bosentan in Children With Idiopathic or Familial Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: bosentan
children
pharmacokinetics
pulmonary arterial hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-04-27
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan
timeFrame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of bosentan and its metabolites
timeFrame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose
measure: Time to reach the maximum plasma concentration (tmax) of bosentan and its metabolites
timeFrame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose
measure: Area under the plasma concentration-time curve during a dose interval (AUCt) for the metabolites of bosentan
timeFrame: At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose
Other outcomes:
Locations:
Study officials:
References:
citation: Beghetti M, Haworth SG, Bonnet D, Barst RJ, Acar P, Fraisse A, Ivy DD, Jais X, Schulze-Neick I, Galie N, Morganti A, Dingemanse J, Kusic-Pajic A, Berger RM. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study. Br J Clin Pharmacol. 2009 Dec;68(6):948-55. doi: 10.1111/j.1365-2125.2009.03532.x.