Back to resultsFUTURE 3 Study Extension (FUTURE 3 Ext)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bosentan
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring pediatric, pulmonary arterial hypertension, bosentan, Tracleer
Eligibility Criteria
Inclusion Criteria:
- Patients who completed the FUTURE 3 core study (AC-052-373) or prematurely discontinued due to PAH-progression, if bosentan was not permanently discontinued
- Patients who tolerated bosentan pediatric formulation and for whom bosentan is considered beneficial at the end of the FUTURE 3 core study (AC-052-373)
- Signed informed consent by the parents or the legal representatives prior to any study-mandated procedure.
Exclusion Criteria:
- Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible bosentan tablet
- Any clinically significant laboratory abnormality that precludes continuation of bosentan therapy
- Pregnancy
- AST and/or ALT values > 3 times the upper limit of normal range (ULN)
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
- Premature and permanent study drug discontinuation during the FUTURE 3 core study (AC-052-373)
- Any major violation of the FUTURE 3 core study (AC-052-373) protocol.
Sites / Locations
- The Children's Hospital - Site 9102
- Children's National Medical Center - Site 9104
- Columbia University Medical Center Children's Hospital of New York Presbyterian - Site 9101
- Royal Children's Hospital Melbourne, Cardiology - Site 5001
- The Republican Scientific-Practical Center "Cardiology" - Site 3001
- Cardiovascular Institute and Fuwai Hospital
- Shanghai Children's Medical Center - Site 5102
- Fakultní nemocnice v Motole, dětské kardiocentrum - Site 3301
- Hopital Necker-Enfants Malades, Service de Cardiologie Pédiatrique - Site 2201
- CHU de Toulouse - Hôpital des Enfants, Service de Cardiologie Pédiatrique - Site 2202
- Deutsches Herzzentrum Kinderkardiologie - Site 1401
- Universitätsklinikum Bonn Abteilung für Kinderkardiologie - Site 1404
- Justus-Liebig-Universität Giessen, Kinderherzzentrum - Site 1403
- Gottsegen György Országos Kardiológiai Intézet, Gyermekszív Központ, Gyermek Kardiológiai osztály - Site 3401
- Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Gyermekgyógyászati Klinika és Gyermekegészségügyi Központ - Site 3402
- CARE Hospitals, Cardiology Dep. Hyderabad - Site 5302
- Schneider Children's Medical Center- Institute of pediatric cardiology - Site 7101
- Università Degli Studi di Padova - Dipartimento di Pediatria - Servizio di Cardiologia Pediatrica - Site 1501
- Ospedale Pediatrico "Bambino Gesù" - Dipartimento Medico Chirurgico di Cardiologia Pediatrica - Site 1502
- Instituto Nacional de Cardiologia (INC) Ignacio Chavez - Site 8401
- Uniwersyteckie Centrum Kliniczne Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca - Site 3604
- Wojewódzki Szpital Specjalistyczny we Wrocławiu Oddział Kardiologii Dziecięcej z pododdziałem Intensywnego Nadzoru Kardiologicznego - Site 3605
- RAMS Institution, Research Institute for complex issues of cardiovascular diseases, Siberian branch of the Russian Academy of Medical Sciences - Site 3805
- Scientific Center of Cardiovascular Surgery named after A.N.Bakulev of the RAMS - Site 3803
- Moscow Scientific Research Institute for Pediatrics and Childrens Surgery of Rosmedtechnologies - Site 3804
- Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies" - Site 3802
- State Educational Institution of Higher Professional Education "Saint Petersburg State Pediatric Medical Academy of Roszdrav" - Site 3801
- Univerzitetska dečja klinika, Služba za kardiologiju - Site 3901
- Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Služba za ispitivanje i lečenje bolesti srca i krvnih sudova - Site 3902
- Department of Paediatric Cardiology University of the Free State - Site 6001
- Division of Paediatric Cardiology, Steve Biko Academic Hospital - Site 6002
- Hospital Universitatario Vall d'Hebron, Neumologia - Site 1907
- Hospital Universitario La Paz - Paediatric Cardiology Department - Site 1906
- Clinical Diagnostic Center - Pediatric Cardiovascular and ANES and Intensive Care Department - Site 4103
- Gusak Ins Urgent and Recovery SUR AMS - Cardiovascular Rehabilitation Pediatric Department - Site 4101
- Gover INS - Scientific Practical Cardiovascular Pediatric Center - MOH Ukraine - Site 4102
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
bosentan 2mg/kg b.i.d.
bosentan 2mg/kg t.i.d.
Arm Description
Patients who received 2 mg/kg bosentan twcie daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients who received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Outcomes
Primary Outcome Measures
Treatment Emergent Adverse Events (AEs) up to 7 Days After Permanent Study Drug Discontinuation
This is the total number of subjects with at least one adverse event (serious or not serious) whether or not causally related to the study drug and presented cumulatively in the FUTURE 3 and FUTURE 3 Extension study. NOTE: FUTURE 3 extension study was exploratory and no primary efficacy and safety endpoints were defined in the protocol. So, this safety outcome measure was selected and reported as primary endpoint here.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01338415
Brief Title
FUTURE 3 Study Extension
Acronym
FUTURE 3 Ext
Official Title
A Prospective, Multicenter, Open-label Extension of FUTURE 3 to Assess the Safety, Tolerability and Efficacy of the Pediatric Formulation of Bosentan Two Versus Three Times a Day in Children With Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 8, 2011 (Actual)
Primary Completion Date
August 13, 2014 (Actual)
Study Completion Date
May 29, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
5. Study Description
Brief Summary
The objectives of the FUTURE 3 Study Extension are to evaluate the long-term safety, tolerability and efficacy of the pediatric formulation of bosentan two versus three times a day in children with Pulmonary Arterial Hypertension (PAH).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
pediatric, pulmonary arterial hypertension, bosentan, Tracleer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bosentan 2mg/kg b.i.d.
Arm Type
Experimental
Arm Description
Patients who received 2 mg/kg bosentan twcie daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Arm Title
bosentan 2mg/kg t.i.d.
Arm Type
Experimental
Arm Description
Patients who received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Intervention Type
Drug
Intervention Name(s)
Bosentan
Other Intervention Name(s)
ACT-050088
Intervention Description
Oral dispersible tablet administered as 2mg/kg two (b.i.d.) or three (t.i.d.) times per day
Primary Outcome Measure Information:
Title
Treatment Emergent Adverse Events (AEs) up to 7 Days After Permanent Study Drug Discontinuation
Description
This is the total number of subjects with at least one adverse event (serious or not serious) whether or not causally related to the study drug and presented cumulatively in the FUTURE 3 and FUTURE 3 Extension study. NOTE: FUTURE 3 extension study was exploratory and no primary efficacy and safety endpoints were defined in the protocol. So, this safety outcome measure was selected and reported as primary endpoint here.
Time Frame
Up to 62 weeks in average
Other Pre-specified Outcome Measures:
Title
Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC)
Description
The WHO FC indicates the severity of Pulmonary Arterial Hypertension: class I (none) to class IV (most severe). Changes from baseline to month 12 and month 18 of treatment with bosentan included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or no change/stable (same FC at baseline and at the post-baseline time point). Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.
Time Frame
At Month 12
Title
Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC)
Description
The WHO FC indicates the severity of Pulmonary Arterial Hypertension: class I (none) to class IV (most severe). Changes from baseline to month 12 and month 18 of treatment with bosentan included: improvement (change from a higher to a lower FC), worsening (change from a lower to a higher FC) or no change/stable (same FC at baseline and at the post-baseline time point). Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.
Time Frame
At Month 18
Title
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS)
Description
The GCIS is a scale used to rate the patient's current overall clinical condition ("Very Good", "Good", "Neither Good or Bad", "Bad", and "Very Bad"). Rating was performed independently by the physician and parents or legal representatives. Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.
Time Frame
At Month 12
Title
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS)
Description
The GCIS is a scale used to rate the patient's current overall clinical condition ("Very Good", "Good", "Neither Good or Bad", "Bad", and "Very Bad"). Rating was performed independently by the physician and parents or legal representatives. Baseline was defined as the last valid assessment performed prior to first study drug intake in the FUTURE 3 core study.
Time Frame
At Month 18
Title
Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days
Description
Number of patients with at least one PAH-worsening component (death, lung transplant, hospitalization due to PAH progression, initiation of new therapy for PAH, new/worsening right heart failure) reported cumulatively over FUTURE 3 core and extension study.
Time Frame
Up to 62 weeks in average
Title
Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days
Description
PAH progression was defined by time elapsed from the first study drug administration in the FUTURE core study to the day of the first occurrence of any of the following PAH worsening events: death, lung transplant, hospitalization due to PAH progression, initiation of new therapy for PAH or new / worsening right heart failure. Subjects without a PAH worsening event were censored at EOT + 7 days. PAH progression was estimated by Kaplan-Meier methodology and expressed by the percentage of participants free of events at different time points.
Time Frame
From baseline to Month 18
Title
Overall Survival
Description
Overall survival was defined as the time elapsed between the first study drug administration and death (any cause) up to end of study (Month 18 survival follow-up), regardless of whether the patient was on study treatment. Patients who died, regardless of the cause of death, were considered to have had an event. Patients last known to have been alive were censored on their date of last contact. Percentage of participants without death at different time points was estimated using Kaplan-Meier methodology.
Time Frame
From baseline to month 18
Title
Exceptional Use Treatment Period (EUTP): Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) up to 7 Days After Permanent Discontinuation of Study Drug
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) up to 7 Days After Permanent Discontinuation of Study Drug
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With AEs Leading to Premature Discontinuation of Study Drug
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Percentage of participants with AEs leading to premature discontinuation of study drug were reported.
Time Frame
Up to 3 years and 4 months
Title
EUTP: Percentage of Participants With SAEs From 7 up to 60 Days After Permanent Discontinuation of Study Drug
Description
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame
From 7 up to 60 days after permanent discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Deaths
Description
Percentage of participants with deaths were reported.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Adverse Events of Special Interest (AESI)
Description
Percentage of participants with AESI including liver abnormalities and anemia were reported.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 7 Days After Permanent Discontinuation of Study Drug
Description
Percentage of participants with treatment-emergent marked laboratory abnormalities were reported.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Liver Function Abnormalities
Description
Percentage of participants with liver function abnormalities: Alanine aminotransferase (ALT) greater than (>)3*upper limit of normal (ULN), ALT/aspartate aminotransferase (AST) >3*ULN, ALT /AST >3*ULN and less than or equal to (<=) 5*ULN, ALT/AST >5*ULN and <=8*ULN, ALT/AST >8*ULN and ALT/AST >3*ULN, total bilirubin >2*ULN and alkaline phosphatase (ALP) <=2*ULN were reported.
Time Frame
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months)
Title
EUTP: Percentage of Participants With Any Time Occurrence of Hemoglobin <=10 Gram Per Deciliter (g/dL) and <=8g/dL Between Baseline and up to 7 Days After End of Treatment (EOT)
Description
Percentage of participants with any time occurrence of hemoglobin (Hgb) less than or equal to (<=) 10 g/dL and 8 g/dL between baseline and up to the last day of treatment + 7 days during EUTP were reported. Here "N" (number of subjects analyzed) signifies subjects who were evaluable for this outcome measure.
Time Frame
Baseline, up to 7 days after end of treatment (up to 3 years and 4 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who completed the FUTURE 3 core study (AC-052-373) or prematurely discontinued due to PAH-progression, if bosentan was not permanently discontinued
Patients who tolerated bosentan pediatric formulation and for whom bosentan is considered beneficial at the end of the FUTURE 3 core study (AC-052-373)
Signed informed consent by the parents or the legal representatives prior to any study-mandated procedure.
Exclusion Criteria:
Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible bosentan tablet
Any clinically significant laboratory abnormality that precludes continuation of bosentan therapy
Pregnancy
AST and/or ALT values > 3 times the upper limit of normal range (ULN)
Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
Premature and permanent study drug discontinuation during the FUTURE 3 core study (AC-052-373)
Any major violation of the FUTURE 3 core study (AC-052-373) protocol.
Facility Information:
Facility Name
The Children's Hospital - Site 9102
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center - Site 9104
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Columbia University Medical Center Children's Hospital of New York Presbyterian - Site 9101
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Royal Children's Hospital Melbourne, Cardiology - Site 5001
City
Parkville
ZIP/Postal Code
3052
Country
Australia
Facility Name
The Republican Scientific-Practical Center "Cardiology" - Site 3001
City
Minsk
ZIP/Postal Code
220036
Country
Belarus
Facility Name
Cardiovascular Institute and Fuwai Hospital
City
Beijing
ZIP/Postal Code
100037
Country
China
Facility Name
Shanghai Children's Medical Center - Site 5102
City
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Fakultní nemocnice v Motole, dětské kardiocentrum - Site 3301
City
Prague
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Hopital Necker-Enfants Malades, Service de Cardiologie Pédiatrique - Site 2201
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
CHU de Toulouse - Hôpital des Enfants, Service de Cardiologie Pédiatrique - Site 2202
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Deutsches Herzzentrum Kinderkardiologie - Site 1401
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitätsklinikum Bonn Abteilung für Kinderkardiologie - Site 1404
City
Bonn
ZIP/Postal Code
53113
Country
Germany
Facility Name
Justus-Liebig-Universität Giessen, Kinderherzzentrum - Site 1403
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Gottsegen György Országos Kardiológiai Intézet, Gyermekszív Központ, Gyermek Kardiológiai osztály - Site 3401
City
Budapest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, Gyermekgyógyászati Klinika és Gyermekegészségügyi Központ - Site 3402
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
CARE Hospitals, Cardiology Dep. Hyderabad - Site 5302
City
Hyderabad
ZIP/Postal Code
500001
Country
India
Facility Name
Schneider Children's Medical Center- Institute of pediatric cardiology - Site 7101
City
Petach Tikvah
ZIP/Postal Code
49202
Country
Israel
Facility Name
Università Degli Studi di Padova - Dipartimento di Pediatria - Servizio di Cardiologia Pediatrica - Site 1501
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Ospedale Pediatrico "Bambino Gesù" - Dipartimento Medico Chirurgico di Cardiologia Pediatrica - Site 1502
City
Rome
ZIP/Postal Code
00193
Country
Italy
Facility Name
Instituto Nacional de Cardiologia (INC) Ignacio Chavez - Site 8401
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Uniwersyteckie Centrum Kliniczne Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca - Site 3604
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny we Wrocławiu Oddział Kardiologii Dziecięcej z pododdziałem Intensywnego Nadzoru Kardiologicznego - Site 3605
City
Wroclaw
ZIP/Postal Code
51-124
Country
Poland
Facility Name
RAMS Institution, Research Institute for complex issues of cardiovascular diseases, Siberian branch of the Russian Academy of Medical Sciences - Site 3805
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
Scientific Center of Cardiovascular Surgery named after A.N.Bakulev of the RAMS - Site 3803
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
Moscow Scientific Research Institute for Pediatrics and Childrens Surgery of Rosmedtechnologies - Site 3804
City
Moscow
ZIP/Postal Code
125412
Country
Russian Federation
Facility Name
Federal State Institution "Federal center of Heart, Blood and Endocrinology named after V.A.Almazov Rosmedtekhnologies" - Site 3802
City
St. Petersberg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
State Educational Institution of Higher Professional Education "Saint Petersburg State Pediatric Medical Academy of Roszdrav" - Site 3801
City
St. Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Univerzitetska dečja klinika, Služba za kardiologiju - Site 3901
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Služba za ispitivanje i lečenje bolesti srca i krvnih sudova - Site 3902
City
Belgrade
ZIP/Postal Code
11070
Country
Serbia
Facility Name
Department of Paediatric Cardiology University of the Free State - Site 6001
City
Bloemfontein
ZIP/Postal Code
9300
Country
South Africa
Facility Name
Division of Paediatric Cardiology, Steve Biko Academic Hospital - Site 6002
City
Pretoria
ZIP/Postal Code
0001
Country
South Africa
Facility Name
Hospital Universitatario Vall d'Hebron, Neumologia - Site 1907
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario La Paz - Paediatric Cardiology Department - Site 1906
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Clinical Diagnostic Center - Pediatric Cardiovascular and ANES and Intensive Care Department - Site 4103
City
Dnepropetrovsk
ZIP/Postal Code
49060
Country
Ukraine
Facility Name
Gusak Ins Urgent and Recovery SUR AMS - Cardiovascular Rehabilitation Pediatric Department - Site 4101
City
Donetsk
ZIP/Postal Code
83045
Country
Ukraine
Facility Name
Gover INS - Scientific Practical Cardiovascular Pediatric Center - MOH Ukraine - Site 4102
City
Kiev
ZIP/Postal Code
01135
Country
Ukraine
12. IPD Sharing Statement
Learn more about this trial
FUTURE 3 Study Extension
We'll reach out to this number within 24 hrs