Bosentan in Children With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— FUTURE-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319267
• Other study ID #: AC-052-365
• Secondary ID: 2004-005157-63
• Status: Completed
• Phase: Phase 3
• First received: April 26, 2006
• Last updated: May 23, 2016
• Start date: May 2005
• Est. completion date: February 2007

Study information

• Verified date: May 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 2007
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 12 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics 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
Pediatric oral formulation of bosentan, i.e., 32 mg dispersible and breakable tablets

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)

Beghetti M, Haworth SG, Bonnet D, Barst RJ, Acar P, Fraisse A, Ivy DD, Jais X, Schulze-Neick I, Galiè N, Morganti A, Dingemanse J, Kusic-Pajic A, Berger RM. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve during a dose interval (AUCt) for bosentan	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 .	At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose	No
Secondary	Maximum plasma concentration (Cmax) of bosentan and its metabolites	Maximum observed plasma concentration for bosentan and its metabolites was directly derived from their respective plasma concentration-time curves.	At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose	No
Secondary	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	No
Secondary	Area under the plasma concentration-time curve during a dose interval (AUCt) for the metabolites of bosentan	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.	At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose	No