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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01223352




Registration number
NCT01223352
Ethics application status
Date submitted
12/10/2010
Date registered
19/10/2010
Date last updated
11/12/2017

Titles & IDs
Public title
Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension
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
Secondary ID [1] 0 0
AC-052-373
Universal Trial Number (UTN)
Trial acronym
FUTURE 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - bosentan

Experimental: 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

Experimental: Bosentan 2 mg/Kg b.i.d. - 2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan
Timepoint [1] 0 0
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

Eligibility
Key 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
Minimum age
3 Months
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/08/2013
Sample size
Target
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Children's Hospital Melbourne, Cardiology - Site 5001 - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
Belarus
State/province [6] 0 0
Minsk
Country [7] 0 0
China
State/province [7] 0 0
Beijing
Country [8] 0 0
China
State/province [8] 0 0
Chengdu
Country [9] 0 0
China
State/province [9] 0 0
Guangdong
Country [10] 0 0
China
State/province [10] 0 0
Shanghai
Country [11] 0 0
Czechia
State/province [11] 0 0
Prague
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Toulouse
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Germany
State/province [15] 0 0
Bonn
Country [16] 0 0
Germany
State/province [16] 0 0
Giessen
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest
Country [18] 0 0
Hungary
State/province [18] 0 0
Szeged
Country [19] 0 0
India
State/province [19] 0 0
Hyderabad
Country [20] 0 0
India
State/province [20] 0 0
New Delhi
Country [21] 0 0
Israel
State/province [21] 0 0
Petach Tikvah
Country [22] 0 0
Italy
State/province [22] 0 0
Padova
Country [23] 0 0
Italy
State/province [23] 0 0
Rome
Country [24] 0 0
Mexico
State/province [24] 0 0
Mexico City
Country [25] 0 0
Mexico
State/province [25] 0 0
Monterrey
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Poland
State/province [27] 0 0
Gdansk
Country [28] 0 0
Poland
State/province [28] 0 0
Lodz
Country [29] 0 0
Poland
State/province [29] 0 0
Warszawa
Country [30] 0 0
Poland
State/province [30] 0 0
Wroclaw
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Kemerovo
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Moscow
Country [33] 0 0
Russian Federation
State/province [33] 0 0
St. Petersberg
Country [34] 0 0
Russian Federation
State/province [34] 0 0
St. Petersburg
Country [35] 0 0
Serbia
State/province [35] 0 0
Belgrade
Country [36] 0 0
South Africa
State/province [36] 0 0
Bloemfontein
Country [37] 0 0
South Africa
State/province [37] 0 0
Durban
Country [38] 0 0
South Africa
State/province [38] 0 0
Pretoria
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Ukraine
State/province [41] 0 0
Dnepropetrovsk
Country [42] 0 0
Ukraine
State/province [42] 0 0
Donetsk
Country [43] 0 0
Ukraine
State/province [43] 0 0
Kiev

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01223352
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andjela Kusic-Pajic, MD
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01223352