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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01223352
• Date of registration: 12/10/2010
• Prospective Registration: Yes
• Primary sponsor: Actelion
• Public title: Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension FUTURE 3
• Scientific title: An Open-label, Prospective Multicenter Study to Assess the Pharmacokinetics, Tolerability, Safety and Efficacy of the Pediatric Formulation of Bosentan Two Versus Three Times a Day in Children With Pulmonary Arterial Hypertension
• Date of first enrolment: March 8, 2011
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01223352
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belarus, China, Czech Republic, Czechia, France, Germany, Hungary, India, Israel, Italy, Mexico, Netherlands, Poland, Russian Federation, Serbia, South Africa, Spain, Ukraine, United States

Contacts

• Name: Andjela Kusic-Pajic, MD
• Affiliation: Actelion

Key inclusion & exclusion 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



Age minimum: 3 Months
Age maximum: 12 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: bosentan

Primary Outcome(s)

Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan [Time Frame: 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]

Secondary ID(s)

AC-052-373

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/06/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01223352