FUTURE-1: Bosentan in Children With Pulmonary Arterial Hypertension

Sponsor

Actelion (Industry)

Overall Status

Completed

CT.gov ID

NCT00319267

Collaborator

(none)

Enrollment

Locations

Arm

21.1

Duration (Months)

3.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Bosentan	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

May 1, 2005

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Feb 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Bosentan Pediatric oral formulation of bosentan, i.e., 32 mg dispersible and breakable tablets Other Names: ACT-050088 Ro 47-0203

Arm

Intervention/Treatment

Experimental: 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.

Drug: Bosentan

Pediatric oral formulation of bosentan, i.e., 32 mg dispersible and breakable tablets

Other Names:

ACT-050088

Ro 47-0203

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital Cardiac Care Center	Denver	Colorado	United States	80218
2	Columbia University Medical Center	New York	New York	United States	10032
3	Hopital Antoine Beclere	Clamart		France	92140
4	Hopital Necker	Paris		France	75743
5	CHE de Toulouse Hopital d'Enfants	Toulouse		France
6	Deutsches Herzzentrum	Augustenburger		Germany
7	Universitats Kinderklinik	Giessen		Germany
8	Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
9	Beatrix Children's Hospital	Groningen		Netherlands
10	Hopital des Enfants	Geneva		Switzerland
11	The Institute of Child Health	London		United Kingdom