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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. - FUTURE 1

Phase 1
Conditions
Idiopathic or familial PAH
Registration Number
EUCTR2004-005157-63-GB
Lead Sponsor
Actelion Pharmaceuticals Ltd.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
Target Recruitment
33
Inclusion Criteria

All patients should start the study drug (bosentan pediatric formulation) at the 2mg/kg b.i.d whether or not they were previously treated with bosentan.

Eligible patients must meet all of the following inclusion criteria during the Screening visit:

· Signed informed consent by the parents or the legal representatives.

· Male or female =2 and < 12 years of age.
Females who are menstruating must have a negative serum pregnancy test. A reliable method of contraception must be considered, if appropriate. If using hormonal contraception, an additional alternative reliable method of contraception must be used.

- Reliable method of contraception are:

Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.

Intra-uterine devices.

Oral, injectable or implantable contraceptives only in combination with a barrier method.

- Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception.

- Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.

. Idiopathic PAH or familial PAH diagnosed by right heart catheterization
(Clinical classification of pulmonary hypertension - Venice 2003).

· WHO functional class II or III. (see Appendix 3 of the protocol).

· 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.

· PAH therapy must have been 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 must have been stable for at least 3 months prior to Screening.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years)
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years)
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients will not be included in the study if any of the following exclusion criteria are present at the Screening visit:

· 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. (See Appendix 1 of the protocol).

· 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. (See Appendix 4 of the protocol).
· 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 clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: The primary endpoint is to demonstrate that the exposure to bosentan in children with IPAH or familial PAH, using a pediatric formulation, is similar to that in adults with PAH.;Secondary Objective: The secondary objective of this study is to evaluate the tolerability and safety of a pediatric formulation of bosentan in this patient population.;Primary end point(s): The main analysis of the primary endpoint is performed on the PK-evaluable set for this equivalence study.
Secondary Outcome Measures
NameTimeMethod
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