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FUTURE 3 Study Extension (FUTURE 3 Ext)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01338415
Recruitment Status : Completed
First Posted : April 19, 2011
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Intervention Drug: Bosentan
Enrollment 58
Recruitment Details Participants in this 1-year extension study were pediatric patients who completed the 6-month randomized open-label core study AC-052-373. In addition, patients were required to have tolerated study treatment during the FUTURE 3 core study and were considered by the investigator to benefit from continued bosentan treatment.
Pre-assignment Details 64 patients were randomized in the FUTURE 3 core study, among whom 58 were enrolled in the FUTURE 3 extension study.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description Patients 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 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
Period Title: Overall Study
Started 33 31
Enrolled in FUTURE 3 Extension 31 27
Completed 23 22
Not Completed 10 9
Reason Not Completed
Adverse Event             8             6
Withdrawal by Subject             1             1
Other (PAH not the main etiology of PH)             0             2
Other (administrative reason)             1             0
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d. Total
Hide Arm/Group Description Patients received 2 mg/kg bosentan b.i.d. during the FUTURE 3 core study and continued with the same dose regimen during the extension study Patients received 2 mg/kg bosentan t.i.d. during the FUTURE 3 core study and continued with the same dose regimen during the extension study Total of all reporting groups
Overall Number of Baseline Participants 33 31 64
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 31 participants 64 participants
4.5  (3.35) 5.2  (3.81) 4.8  (3.57)
[1]
Measure Description: Age at randomization in the FUTURE 3 core study (AC-052-373)
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Age Categories as per protocol Number Analyzed 33 participants 31 participants 64 participants
Infants and toddlers (28 days-23 months)
10
  30.3%
11
  35.5%
21
  32.8%
Children (2-11 years)
23
  69.7%
20
  64.5%
43
  67.2%
[1]
Measure Description: Number of subjects in each age category at randomization in the FUTURE 3 core study (AC-052-373)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
Female
18
  54.5%
10
  32.3%
28
  43.8%
Male
15
  45.5%
21
  67.7%
36
  56.3%
[1]
Measure Description: Number of males and females randomized in the FUTURE 3 core study (AC-052-373)
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race as per protocol Number Analyzed 33 participants 31 participants 64 participants
Caucasian/White
25
  75.8%
23
  74.2%
48
  75.0%
Black
1
   3.0%
2
   6.5%
3
   4.7%
Asian
6
  18.2%
4
  12.9%
10
  15.6%
Hispanic
0
   0.0%
1
   3.2%
1
   1.6%
Other
1
   3.0%
1
   3.2%
2
   3.1%
Pulmonary Arterial Hypertension (PAH) etiology   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
Idiopathic
14
  42.4%
15
  48.4%
29
  45.3%
Heritable
2
   6.1%
0
   0.0%
2
   3.1%
Congenital heart disease
6
  18.2%
2
   6.5%
8
  12.5%
Associated PAH (i.e.,PAH after surgery for CHD)
11
  33.3%
13
  41.9%
24
  37.5%
Missing
0
   0.0%
1
   3.2%
1
   1.6%
[1]
Measure Description: Children had a diagnosis of PAH belonging to one of the following categories: - Idiopathic PAH - Heritable PAH - Associated PAH persisting after complete repair of a congenital heart defect - PAH-congenital heart disease (PAH-CHD) associated with open shunts
World Health Organization functional class (WHO FC)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 31 participants 64 participants
FC I
9
  27.3%
10
  32.3%
19
  29.7%
FC II
12
  36.4%
15
  48.4%
27
  42.2%
FC III
12
  36.4%
6
  19.4%
18
  28.1%
[1]
Measure Description: The World Health Organization (WHO) defines 4 classes to classify the functional status of patients with pulmonary hypertension: Class I (FC I): No limitation of physical activity; Class II (FC II): Slight limitation of physical activity; Class III (FC III): Marked limitation of physical activity; Class IV (FC IV): Inability to carry out any physical activity without symptoms.
1.Primary Outcome
Title Treatment Emergent Adverse Events (AEs) up to 7 Days After Permanent Study Drug Discontinuation
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Safety population analysis set, including all patients who received at least one dose of study treatment and evaluated according to the study treatment that they received.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 33 31
Measure Type: Count of Participants
Unit of Measure: Participants
29
  87.9%
26
  83.9%
2.Other Pre-specified Outcome
Title Change From Baseline up to 12 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population was used. Where a missing visit score exists between two visits with scores, the missing score was imputed with the worse score of the non-missing scores; if the missing score was not between 2 visits with scores, it was replaced by the last non-missing score.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 33 31
Measure Type: Count of Participants
Unit of Measure: Participants
Stable WHO FC
22
  66.7%
25
  80.6%
Improved WHO FC
7
  21.2%
3
   9.7%
Worsened WHO FC
4
  12.1%
3
   9.7%
3.Other Pre-specified Outcome
Title Change From Baseline up to 18 Months of Study Treatment in the World Health Organization Functional Classification (WHO FC)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population was used. Where a missing visit score exists between two visits with scores, the missing score was imputed with the worse score of the non-missing scores; if the missing score was not between 2 visits with scores, it was replaced by the last non-missing score.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients 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 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
Overall Number of Participants Analyzed 33 31
Measure Type: Count of Participants
Unit of Measure: Participants
Stable WHO FC
25
  75.8%
25
  80.6%
Improved WHO FC
3
   9.1%
3
   9.7%
Worsened WHO FC
5
  15.2%
3
   9.7%
4.Other Pre-specified Outcome
Title Change From Baseline up to 12 Months of Study Treatment in the Global Clinical Impression Scale (GCIS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population was used for these analyses. No imputation method was used. Only patients with available results at the corresponding time point are included in the analysis.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 28 23
Measure Type: Count of Participants
Unit of Measure: Participants
Assessment by Physician Stable
16
  57.1%
16
  69.6%
Improved
10
  35.7%
6
  26.1%
Worsened
2
   7.1%
1
   4.3%
Assessment by Parents/Legal representative Stable
16
  57.1%
12
  52.2%
Improved
9
  32.1%
11
  47.8%
Worsened
3
  10.7%
0
   0.0%
5.Other Pre-specified Outcome
Title Change From Baseline up to 18 Months of Study Treatment in the Global Clinical Impression Scale (GCIS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population was used. No imputation method was used. Only patients with available results at the corresponding time point are including in the analysis.
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 19 18
Measure Type: Count of Participants
Unit of Measure: Participants
Assessment by Physician Stable
9
  47.4%
12
  66.7%
Improved
6
  31.6%
5
  27.8%
Worsened
4
  21.1%
1
   5.6%
Assessment by Parents/Legal representtive Stable
8
  42.1%
7
  38.9%
Improved
6
  31.6%
10
  55.6%
Worsened
5
  26.3%
1
   5.6%
6.Other Pre-specified Outcome
Title Number of Patients With Pulmonary Arterial Hypertension (PAH) Worsening Components up to the Last Day of Treatment + 7 Days
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population was used
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 33 31
Measure Type: Count of Participants
Unit of Measure: Participants
At least one PAH-worsening event
10
  30.3%
5
  16.1%
No PAH-worsening event
23
  69.7%
26
  83.9%
7.Other Pre-specified Outcome
Title Pulmonary Arterial Hypertension (PAH) Progression up to End of Treatment + 7 Days
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
These are the numbers of patients at risk at the time of study treatment initiation in the FUTURE 3 core study
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 33 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients free of events
Kaplan-Meier estimate at Month 12
74.9
(56.0 to 86.6)
88.9
(69.4 to 96.3)
Kaplan-Meier estimate at Month 18
68.2
(48.9 to 81.5)
81.0
(60.1 to 91.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Cox proportional hazard regression univariate model with treatment as covariate (treatment-only univariate model)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.438
Confidence Interval (2-Sided) 95%
0.470 to 4.399
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Cox proportional hazard regression univariate model with WHO FC at baseline (FC III vs FC I/II) as covariate
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0526
Comments p-value <= 10% indicates that the covariate WHO FC at baseline is related to the time to PAH worsening
Method Regression, Cox
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Treatment Hazard Ratio (HR) in the multivariate model with treatment and WHO FC at baseline as covariates
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.169
Confidence Interval 95%
0.371 to 3.681
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Test of improvement in model fit from the univariate to the multivariate model with WHO FC at baseline as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments p-value <= 10% indicates an improvement in model fit
Method log(e) likelihood ratio
Comments [Not Specified]
8.Other Pre-specified Outcome
Title Overall Survival
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
These are the numbers of patients at risk at the time of study treatment initiation in the FUTURE 3 core study
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d.
Hide Arm/Group Description:
Patients received 2 mg/kg bosentan twice daily (b.i.d.) during the FUTURE 3 core study and continued with the same dose regimen during the extension study
Patients received 2 mg/kg bosentan 3 times a day (t.i.d.) during the FUTURE 3 core study continued with the same dose regimen during the extension study
Overall Number of Participants Analyzed 33 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Kaplan-Meier estimate at Month 12
81.8
(63.9 to 91.4)
90.0
(72.1 to 96.7)
Kaplan-Meier estimate at Month 18
75.8
(57.3 to 87.1)
86.5
(68.0 to 94.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Cox proportional hazard regression univariate model with treatment as covariate (treatment-only univariate model)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.935
Confidence Interval (2-Sided) 95%
0.582 to 6.428
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Cox proportional hazard regression univariate model with WHO FC at baseline (FC III vs FC I/II) as covariate
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments [Not Specified]
Method Regression, Cox
Comments p-value <= 10% indicates that the covariate is related to the time to the time to death up to end-of-study
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Post-hoc analysis: Treatment Hazard Ratio (HR) in the multivariate model with treatment and WHO FC at baseline as covariates
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.487
Confidence Interval (2-Sided) 95%
0.437 to 5.052
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bosentan 2mg/kg b.i.d., Bosentan 2mg/kg t.i.d.
Comments Test of the improvement in model fit from the univariate to the multivariate model with WHO FC at baseline as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method log(e) likelihood ratio
Comments p-value <= 10% indicates an improvement in model fit
Time Frame From baseline up to end of treatment (and up to additional 60 days for serious adverse events and deaths), i.e. an average of 62 weeks
Adverse Event Reporting Description Adverse events are reported cumulatively for the FUTURE 3 core and extension studies
 
Arm/Group Title Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d
Hide Arm/Group Description 2 mg/kg bosentan was administered twice daily for a cumulative mean (± SD) duration of 64.1 ± 3.38 weeks (FUTURE 3 core + extension studies) 2 mg/kg bosentan was administered 3 times a day for a cumulative mean (± SD) duration of 60.4 ± 4.20 weeks (FUTURE 3 core + extension studies)
All-Cause Mortality
Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d
Affected / at Risk (%) Affected / at Risk (%)
Total   8/33 (24.24%)      4/31 (12.90%)    
Show Serious Adverse Events Hide Serious Adverse Events
Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/33 (45.45%)      13/31 (41.94%)    
Cardiac disorders     
CARDIAC ARREST  1  1/33 (3.03%)  1 0/31 (0.00%)  0
CARDIAC FAILURE  1  1/33 (3.03%)  2 0/31 (0.00%)  0
CARDIAC FAILURE ACUTE  1  0/33 (0.00%)  0 1/31 (3.23%)  1
CARDIOPULMONARY FAILURE  1  1/33 (3.03%)  1 1/31 (3.23%)  1
CYANOSIS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
Congenital, familial and genetic disorders     
MUCOPOLYSACCHARIDOSIS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
Gastrointestinal disorders     
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/33 (0.00%)  0 1/31 (3.23%)  1
General disorders     
DEATH  1  1/33 (3.03%)  1 0/31 (0.00%)  0
MULTI-ORGAN FAILURE  1  1/33 (3.03%)  1 0/31 (0.00%)  0
PYREXIA  1  0/33 (0.00%)  0 1/31 (3.23%)  2
Immune system disorders     
DRUG HYPERSENSITIVITY  1  1/33 (3.03%)  1 0/31 (0.00%)  0
Infections and infestations     
BRONCHITIS  1  1/33 (3.03%)  1 0/31 (0.00%)  0
BRONCHOPNEUMONIA  1  0/33 (0.00%)  0 2/31 (6.45%)  2
GASTROENTERITIS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
GASTROENTERITIS ADENOVIRUS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
GASTROENTERITIS ROTAVIRUS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
INFECTION  1  1/33 (3.03%)  1 0/31 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION VIRAL  1  1/33 (3.03%)  1 0/31 (0.00%)  0
PNEUMONIA  1  1/33 (3.03%)  1 3/31 (9.68%)  3
RESPIRATORY TRACT INFECTION VIRAL  1  0/33 (0.00%)  0 1/31 (3.23%)  1
VIRAL INFECTION  1  0/33 (0.00%)  0 1/31 (3.23%)  1
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  1/33 (3.03%)  1 0/31 (0.00%)  0
Injury, poisoning and procedural complications     
FALL  1  0/33 (0.00%)  0 1/31 (3.23%)  1
HEAD INJURY  1  0/33 (0.00%)  0 1/31 (3.23%)  1
Investigations     
BODY TEMPERATURE INCREASED  1  0/33 (0.00%)  0 1/31 (3.23%)  1
OXYGEN SATURATION DECREASED  1  0/33 (0.00%)  0 1/31 (3.23%)  1
Metabolism and nutrition disorders     
METABOLIC DISORDER  1  1/33 (3.03%)  1 0/31 (0.00%)  0
Nervous system disorders     
CONVULSION  1  0/33 (0.00%)  0 1/31 (3.23%)  4
LOSS OF CONSCIOUSNESS  1  1/33 (3.03%)  1 0/31 (0.00%)  0
MIGRAINE WITH AURA  1  1/33 (3.03%)  1 0/31 (0.00%)  0
SYNCOPE  1  2/33 (6.06%)  3 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ADENOIDAL HYPERTROPHY  1  1/33 (3.03%)  1 0/31 (0.00%)  0
EPISTAXIS  1  1/33 (3.03%)  1 0/31 (0.00%)  0
PULMONARY ARTERIAL HYPERTENSION  1  4/33 (12.12%)  4 2/31 (6.45%)  2
PULMONARY EMBOLISM  1  1/33 (3.03%)  1 0/31 (0.00%)  0
PULMONARY HYPERTENSIVE CRISIS  1  0/33 (0.00%)  0 1/31 (3.23%)  2
RESPIRATORY DISTRESS  1  0/33 (0.00%)  0 1/31 (3.23%)  1
Surgical and medical procedures     
ATRIAL SEPTAL DEFECT REPAIR  1  0/33 (0.00%)  0 1/31 (3.23%)  1
CARDIAC OPERATION  1  1/33 (3.03%)  1 0/31 (0.00%)  0
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bosentan 2mg/kg b.i.d. Bosentan 2mg/kg t.i.d
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/33 (72.73%)      23/31 (74.19%)    
Blood and lymphatic system disorders     
THROMBOCYTOPENIA  1  2/33 (6.06%)  2 0/31 (0.00%)  0
Gastrointestinal disorders     
ABDOMINAL PAIN  1  1/33 (3.03%)  1 2/31 (6.45%)  2
CONSTIPATION  1  1/33 (3.03%)  1 3/31 (9.68%)  4
DIARRHOEA  1  2/33 (6.06%)  2 6/31 (19.35%)  9
VOMITING  1  4/33 (12.12%)  5 6/31 (19.35%)  10
General disorders     
OEDEMA PERIPHERAL  1  2/33 (6.06%)  2 0/31 (0.00%)  0
PYREXIA  1  5/33 (15.15%)  15 7/31 (22.58%)  15
Immune system disorders     
SEASONAL ALLERGY  1  0/33 (0.00%)  0 2/31 (6.45%)  2
Infections and infestations     
BRONCHITIS  1  3/33 (9.09%)  4 2/31 (6.45%)  2
EAR INFECTION  1  2/33 (6.06%)  2 0/31 (0.00%)  0
GASTROENTERITIS  1  3/33 (9.09%)  3 3/31 (9.68%)  3
INFLUENZA  1  0/33 (0.00%)  0 2/31 (6.45%)  2
LARYNGITIS  1  2/33 (6.06%)  4 0/31 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  1/33 (3.03%)  1 2/31 (6.45%)  2
NASOPHARYNGITIS  1  6/33 (18.18%)  16 5/31 (16.13%)  8
OTITIS MEDIA  1  2/33 (6.06%)  5 1/31 (3.23%)  1
OTITIS MEDIA CHRONIC  1  2/33 (6.06%)  2 0/31 (0.00%)  0
PHARYNGITIS  1  2/33 (6.06%)  3 0/31 (0.00%)  0
RESPIRATORY TRACT INFECTION  1  2/33 (6.06%)  3 1/31 (3.23%)  2
RHINITIS  1  0/33 (0.00%)  0 2/31 (6.45%)  3
TONSILLITIS  1  0/33 (0.00%)  0 2/31 (6.45%)  2
UPPER RESPIRATORY TRACT INFECTION  1  9/33 (27.27%)  22 13/31 (41.94%)  26
VIRAL INFECTION  1  2/33 (6.06%)  2 1/31 (3.23%)  1
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  4/33 (12.12%)  6 3/31 (9.68%)  3
Injury, poisoning and procedural complications     
ACCIDENTAL OVERDOSE  1  0/33 (0.00%)  0 2/31 (6.45%)  2
Investigations     
BLOOD BILIRUBIN INCREASED  1  2/33 (6.06%)  2 1/31 (3.23%)  1
LIVER FUNCTION TEST ABNORMAL  1  0/33 (0.00%)  0 2/31 (6.45%)  2
Respiratory, thoracic and mediastinal disorders     
COUGH  1  4/33 (12.12%)  4 3/31 (9.68%)  3
EPISTAXIS  1  0/33 (0.00%)  0 3/31 (9.68%)  4
NASAL CONGESTION  1  0/33 (0.00%)  0 2/31 (6.45%)  2
PULMONARY ARTERIAL HYPERTENSION  1  2/33 (6.06%)  2 0/31 (0.00%)  0
RHINORRHOEA  1  3/33 (9.09%)  3 0/31 (0.00%)  0
Skin and subcutaneous tissue disorders     
DERMATITIS ALLERGIC  1  0/33 (0.00%)  0 2/31 (6.45%)  2
RASH  1  1/33 (3.03%)  1 2/31 (6.45%)  2
URTICARIA  1  0/33 (0.00%)  0 2/31 (6.45%)  2
Vascular disorders     
FLUSHING  1  0/33 (0.00%)  0 2/31 (6.45%)  2
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any study-related article or abstract written independently by investigators must be submitted to Actelion for review at least 60 days prior to submission for publication or presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: clinical trial disclosure desk
Organization: Actelion Pharmaceuticals Ltd
EMail: clinical-trials-disclosure@actelion.com
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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01338415     History of Changes
Other Study ID Numbers: AC-052-374
2010-021793-12 ( EudraCT Number )
First Submitted: April 15, 2011
First Posted: April 19, 2011
Results First Submitted: September 20, 2017
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017