Bosentan in Children With Pulmonary Arterial Hypertension

NCT00319267 | Completed Phase 3

• 2 other identifiers: AC-052-3652004-005157-63
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

bosentan; children; pharmacokinetics; pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Maximum plasma concentration (Cmax) of bosentan and its metabolites

  At pre-dose and 0.5h, 1h, 3h, 7.5h, and 12h post-dose

• 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

Study Arms (1)

Bosentan

EXPERIMENTAL

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

Interventions

Bosentan DRUG

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

Also known as: ACT-050088, Ro 47-0203

Bosentan

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• 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.

  PMID: 20002090 RESULT

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2006
• First Posted: April 27, 2006
• Study Start: May 1, 2005
• Primary Completion: December 1, 2006
• Study Completion: February 1, 2007
• Last Updated: February 3, 2025

Record last verified: 2025-01