Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) |
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. |
At Month 12 |
|
| Other |
Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC) |
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. |
At Month 18 |
|
| Other |
Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) |
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. |
At Month 12 |
|
| Other |
Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS) |
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. |
At Month 18 |
|
| Other |
Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days |
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. |
Up to 62 weeks in average |
|
| Other |
Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days |
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. |
From baseline to Month 18 |
|
| Other |
Overall Survival |
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. |
From baseline to month 18 |
|
| Other |
Exceptional Use Treatment Period (EUTP): Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) up to 7 Days After Permanent Discontinuation of Study Drug |
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. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) up to 7 Days After Permanent Discontinuation of Study Drug |
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. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With AEs Leading to Premature Discontinuation of Study Drug |
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. |
Up to 3 years and 4 months |
|
| Other |
EUTP: Percentage of Participants With SAEs From 7 up to 60 Days After Permanent Discontinuation of Study Drug |
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. |
From 7 up to 60 days after permanent discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With Deaths |
Percentage of participants with deaths were reported. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With Adverse Events of Special Interest (AESI) |
Percentage of participants with AESI including liver abnormalities and anemia were reported. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 7 Days After Permanent Discontinuation of Study Drug |
Percentage of participants with treatment-emergent marked laboratory abnormalities were reported. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
EUTP: Percentage of Participants With Liver Function Abnormalities |
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. |
Up to 7 days after discontinuation of study drug (up to 3 years and 4 months) |
|
| Other |
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) |
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. |
Baseline, up to 7 days after end of treatment (up to 3 years and 4 months) |
|
| Primary |
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. |
Up to 62 weeks in average |
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