A 5-month research project for children aged from 1 year to 17 years who have high blood pressure in the lung, to see how well bosentan decreases this high blood pressure and improves children's physical capabilities compared to an inactive compound

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2011-004106-16-FR
• Date of registration: 17/02/2012
• Prospective Registration: Yes
• Primary sponsor: Actelion pharmaceuticals Ltd
• Public title: A 5-month research project for children aged from 1 year to 17 years who have high blood pressure in the lung, to see how well bosentan decreases this high blood pressure and improves children's physical capabilities compared to an inactive compound
• Scientific title: A randomized, prospective, double-blind, placebo-controlled, group sequential multicenter study to assess efficacy, safety, and tolerability of the pediatric formulation of bosentan in children with pulmonary arterial hypertension - FUTURE 5
• Target sample size: 105
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004106-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Prospective, group sequential If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Bulgaria, Chile, China, Colombia, Croatia, France, Guatemala, India, Malaysia, Mexico, Netherlands, Peru, Philippines, Portugal, Russian Federation, Serbia, Singapore, South Africa, Taiwan, Ukraine, United States, Vietnam

Contacts

• Name: GLOBAL MEDICAL INFORMATION
• Affiliation: Actelion Pharmaceuticals Ltd.

• Name: GLOBAL MEDICAL INFORMATION
• Affiliation: Actelion Pharmaceuticals Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent by the parents or legal representatives prior to any study mandated procedure.

2. Male or female = 1 year and < 17 years of age (maximum age
at randomization is 16 years and 9 months).

3. WHO functional class I–IV.

4. PAH diagnosed with Right Heart Catheterization (RHC).

5. PAH etiologies:
Idiopathic or heritable PAH,
or
Associated PAH persisting/recurrent for at least 6 months
after complete repair of a congenital heart defect,
or
CHD (PAH associated with systemic-to-pulmonary shunts
including Eisenmenger syndrome).

6. PVR > 3 Wood units for idiopathic, heritable PAH or PAH
persisting/recurrent after complete repaired of congenital
heart defect.
or
PVR > 8 Wood units for PAH associated with systemic-to-pulmonary open shunts with a ratio Qp/Qs < 2.

7. Body weight = 8 kg and = 95 kg.

8. Patients naïve to PAH-specific treatment
or
Patients already treated with PAH-specific medication at a stable dose since at least 3 months:
Prostanoids, PDE-5 inhibitors
No combination of PAH-specific therapy is allowed.

9. Patients naïve to PAH related, non-specific medication
or
Patients already treated with PAH related, non-specific medication, such as
Calcium channel blockers (stable dose since at least 3 months)
Anticoagulants
Diuretics
Digoxin

10. Females of childbearing potential must have a negative
pre-treatment pregnancy test and must use reliable methods of
contraception during the whole treatment period and for 1 month after study drug discontinuation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 105
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Non-stable disease status, e.g., history of recurrent (near-)
syncope or signs and symptoms of non-compensated right heart failure.

2. Patients with bronchopulmonary dysplasia, congenital
diaphragmatic hernia or other chronic lung diseases.

3. Need or plan to wean patient from any PAH-specific therapies
during the study.

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

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

6. Moderate or 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 bosentan dispersible tablet.

9. Treatment with bosentan or any other endothelin receptor
antagonists within 4 months prior to randomization (including any ERA investigational drug).

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

11. Pregnancy or breastfeeding.

12. Any condition that prevents compliance with the protocol or
adherence to therapy.

13. Administration of prohibited medication within 2 weeks or
5 times the half-life, prior to randomization, whichever is the
longest.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension (PAH) in children
MedDRA version: 14.1 Level: LLT Classification code 10064908 Term: Associated with (APAH) System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 14.1 Level: LLT Classification code 10064909 Term: Idiopathic (IPAH) System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 14.1 Level: LLT Classification code 10064910 Term: Familial (FPAH) System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Tracleer
Product Name: bosentan
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: bosentan
CAS Number: 157212-55-0
Current Sponsor code: ACT-050088
Other descriptive name: BOSENTAN MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 32-
Pharmaceutical form of the placebo: Dispersible tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: See above

Secondary Objective: The other objectives are to evaluate the following in this patient population:
- Other hemodynamic variables, WHO functional class, global clinical status, exercise capacity, time to clinical worsening.
- Tolerability and safety variables.
- Echocardiographic variables (imaging and Doppler evaluation).
- The steady-state PK of the bosentan dispersible tablet formulation at doses of 0.5 mg/kg b.i.d. and 2 mg/kg b.i.d.
- The PK-efficacy relationship on PVRi and other selected efficacy endpoints.

Primary end point(s): Primary efficacy endpoint = PVRi at Week 12 expressed as percent change from the baseline value.
‘baseline’ is defined as the last assessment performed prior to first study drug intake.

Main Objective: The primary objective is to demonstrate that 12 weeks of treatment with either dose (0.5 mg/kg b.i.d or 2 mg/kg b.i.d) of the bosentan dispersible tablet formulation improves PVRi in pediatric patients with PAH, aged from = 1 year to < 17 years.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See above

Secondary end point(s): Secondary efficacy endpoints = Change from baseline to Week 12 in RHC variables.

Secondary ID(s)

2011-004106-16-NL

AC-052-375

Source(s) of Monetary Support

Actelion Pharmaceuticals Ltd.