Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension (FUTURE 3)

Actelion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: bosentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01223352

AC-052-373

Details and patient eligibility

About

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.

Enrollment: 64 patients

Sex: All

Ages: 3 months to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

64 participants in 2 patient groups

Bosentan 2 mg/Kg t.i.d.

Experimental group

Description:

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

Treatment:

Drug: bosentan

Bosentan 2 mg/Kg b.i.d.

Experimental group

Description:

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

Treatment:

Drug: bosentan