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

NCT ID: NCT01223352

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-08
• Study Completion Date: 2013-08-19

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bosentan 2 mg/Kg t.i.d.

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

Group Type: EXPERIMENTAL

bosentan

Intervention Type: 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.

Bosentan 2 mg/Kg b.i.d.

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

Group Type: EXPERIMENTAL

bosentan

Intervention Type: 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.

Interventions

bosentan

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.

Intervention Type: DRUG

Other Intervention Names

Tracleer; ACT-050088

Eligibility Criteria

Inclusion Criteria

1. 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)

2. World Health Organization functional Class (WHO FC) I, II or III

3. Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)

4. Body weight ≥ 3.5 kg

5. Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)

6. 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

7. Signed informed consent by the parents or legal representatives

Exclusion Criteria

1. PAH etiologies other than listed above

2. Non-stable disease status

3. Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost

4. Systolic blood pressure < 80% of the lower limit of normal range

5. Aspartate aminotransferase and/or alanine aminotransferase values > 1.5 times the upper limit of normal range.

6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C

7. Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.

8. Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet

9. 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)
• Ritonavir
• Co-administration of CYP2C9 inhibitors (e.g., amiodarone, voriconazole) and moderate/strong CYP3A4 inhibitors (e.g., amprenavir, erythromycin, ketoconazole, diltiazem, itraconazole)
• Endothelin receptor antagonists (ERAs) other than bosentan

10. Treatment with another investigational drug within 1 month prior to randomization or planned treatment

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andjela Kusic-Pajic, MD

Role: STUDY_DIRECTOR

Actelion

Other Identifiers

AC-052-373

Identifier Type: -

Identifier Source: org_study_id