FUTURE 3 Study Extension (FUTURE 3 Ext)
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| ClinicalTrials.gov Identifier: NCT01338415 |
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Recruitment Status :
Completed
First Posted : April 19, 2011
Results First Posted : December 11, 2017
Last Update Posted : June 16, 2021
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Sponsor:
Actelion
Information provided by (Responsible Party):
Actelion
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Arterial Hypertension | Drug: Bosentan | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 58 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 8, 2011 |
| Actual Primary Completion Date : | August 13, 2014 |
| Actual Study Completion Date : | May 29, 2020 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Bosentan
| Arm | Intervention/treatment |
|---|---|
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Experimental: bosentan 2mg/kg b.i.d.
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
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Drug: Bosentan
Oral dispersible tablet administered as 2mg/kg two (b.i.d.) or three (t.i.d.) times per day
Other Name: ACT-050088 |
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Experimental: bosentan 2mg/kg t.i.d.
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
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Drug: Bosentan
Oral dispersible tablet administered as 2mg/kg two (b.i.d.) or three (t.i.d.) times per day
Other Name: ACT-050088 |
Primary Outcome Measures :
- Treatment Emergent Adverse Events (AEs) up to 7 Days After Permanent Study Drug Discontinuation [ Time Frame: Up to 62 weeks in average ]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.
Other Outcome Measures:
- Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) [ Time Frame: At Month 12 ]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.
- Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) [ Time Frame: At Month 18 ]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.
- Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) [ Time Frame: At Month 12 ]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.
- Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) [ Time Frame: At Month 18 ]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.
- Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days [ Time Frame: Up to 62 weeks in average ]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.
- Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days [ Time Frame: From baseline to Month 18 ]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.
- Overall Survival [ Time Frame: From baseline to month 18 ]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.
- Exceptional Use Treatment Period (EUTP): Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) up to 7 Days After Permanent Discontinuation of Study Drug [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]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.
- EUTP: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) up to 7 Days After Permanent Discontinuation of Study Drug [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]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.
- EUTP: Percentage of Participants With AEs Leading to Premature Discontinuation of Study Drug [ Time Frame: Up to 3 years and 4 months ]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.
- EUTP: Percentage of Participants With SAEs From 7 up to 60 Days After Permanent Discontinuation of Study Drug [ Time Frame: From 7 up to 60 days after permanent discontinuation of study drug (up to 3 years and 4 months) ]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.
- EUTP: Percentage of Participants With Deaths [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]Percentage of participants with deaths were reported.
- EUTP: Percentage of Participants With Adverse Events of Special Interest (AESI) [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]Percentage of participants with AESI including liver abnormalities and anemia were reported.
- EUTP: Percentage of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 7 Days After Permanent Discontinuation of Study Drug [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]Percentage of participants with treatment-emergent marked laboratory abnormalities were reported.
- EUTP: Percentage of Participants With Liver Function Abnormalities [ Time Frame: Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) ]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.
- 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) [ Time Frame: Baseline, up to 7 days after end of treatment (up to 3 years and 4 months) ]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.
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| Ages Eligible for Study: | 3 Months to 12 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01338415
Locations
Show 36 study locations
Sponsors and Collaborators
Actelion
| Responsible Party: | Actelion |
| ClinicalTrials.gov Identifier: | NCT01338415 |
| Other Study ID Numbers: |
AC-052-374 2010-021793-12 ( EudraCT Number ) |
| First Posted: | April 19, 2011 Key Record Dates |
| Results First Posted: | December 11, 2017 |
| Last Update Posted: | June 16, 2021 |
| Last Verified: | May 2021 |
Keywords provided by Actelion:
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pediatric pulmonary arterial hypertension bosentan Tracleer |
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension Familial Primary Pulmonary Hypertension Hypertension Vascular Diseases Cardiovascular Diseases Hypertension, Pulmonary |
Lung Diseases Respiratory Tract Diseases Bosentan Antihypertensive Agents Endothelin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |