Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension

NCT01223352 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AC-052-373
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of AC-052-373 was to assess the pharmacokinetic (PK) profile of two dosing regimens of the pediatric formulation of bosentan in children with pulmonary arterial hypertension (PAH) \<12 years of age.

Conditions

Pulmonary Arterial Hypertension

Keywords

pulmonary arterial hypertension; children; pediatric; bosentan

Outcome Measures

Primary Outcomes (1)

• Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan

  Daily exposure was measured by the area under the plasma concentration-time curve over a period of 24 hours \[AUC(0-24)\]. Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. AUC(0-24) was calculated as a multiple of AUCtau, which is the AUC over a dosing interval (AUCtau x 2 for the b.i.d. dosing regimen and AUCtau x 3 for the t.i.d. regimen). As the smallest dose unit was 8 mg (1/4 tablet), it was not possible to achieve the exact target dose of 2 mg/kg. Therefore, AUC(0-24) was corrected to 2 mg/kg (target dose) \[AUC(0-24c)\].

  0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment

Other Outcomes (7)

• Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan

  0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment

• Time to Reach Cmax [Tmax] of Bosentan

  0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment

• Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056)

  0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment

Study Arms (2)

Bosentan 2 mg/Kg t.i.d.

EXPERIMENTAL

2 mg/kg bosentan administered three times a day (morning, afternoon, evening) for a planned duration of 24 weeks

Drug: bosentan

Bosentan 2 mg/Kg b.i.d.

EXPERIMENTAL

2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks

Drug: bosentan

Interventions

bosentan DRUG

32 mg quadrisected dispersible tablet. The dosage of bosentan (2 mg/Kg) was adjusted according to the patient's body weight at initiation of the study treatment. Dosage readjustment was permitted after 12 weeks of treatment.

Also known as: Tracleer, ACT-050088

Bosentan 2 mg/Kg b.i.d.; Bosentan 2 mg/Kg t.i.d.

Eligibility Criteria

• Age: 3 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• PAH diagnosis confirmed with right heart catheterization (RHC):
• Idiopathic or heritable PAH, or
• Associated PAH persisting after complete repair of a congenital heart defect (PAH has to be persistent for at least 6 months after surgery) or
• PAH-Congenital Heart Disease (PAH-CHD) associated with systemic-to-pulmonary shunts (after global amendment dated 09 May 2012)
• World Health Organization functional Class (WHO FC) I, II or III
• Male or female ≥ 3 months and \< 12 years of age (maximum age at randomization is 11.5 years)
• Body weight ≥ 3.5 kg
• Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)
• Baseline PAH-therapy (Calcium channel blocker, bosentan, prostanoid, phosphodiesterase type-5 inhibitor) if present, has to be stable for at least 3 months prior to screening. During the study, all background treatments should remain stable
• Signed informed consent by the parents or legal representatives

You may not qualify if:

• PAH etiologies other than listed above
• Non-stable disease status
• Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
• Systolic blood pressure \< 80% of the lower limit of normal range
• Aspartate aminotransferase and/or alanine aminotransferase values \> 1.5 times the upper limit of normal range.
• 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 range.
• Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet
• Treatment with forbidden medication within 2 weeks or at least 5 times the half-life prior to randomization, whichever is the longest:
• Glibenclamide (glyburide)
• Cyclosporin A
• Sirolimus
• Tacrolimus
• Fluconazole
• Rifampicin (rifampin)

Sponsors & Collaborators

• Actelion: lead

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

Results Point of Contact

• Title: clinical trial disclosure desk
• Organization: Actelion Pharmaceuticals Ltd

clinical-trials-disclosure@actelion.com

Study Officials

• Andjela Kusic-Pajic, MD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 12, 2010
• First Posted: October 19, 2010
• Study Start: March 8, 2011
• Primary Completion: April 3, 2013
• Study Completion: August 19, 2013
• Last Updated: February 4, 2025
• Results First Posted: June 29, 2017

Record last verified: 2025-01