FUTURE 2: Bosentan in Children With Pulmonary Arterial Hypertension Extension Study
Sponsor
Actelion (Industry)
Overall Status
Completed
CT.gov ID
NCT00319020
Collaborator
(none)
33
11
1
74.2
3
0
Study Details
Study Description
Brief Summary
The main objective of the FUTURE 2 study was to assess the long-term safety and tolerability of the pediatric formulation of bosentan in children with idiopathic pulmonary arterial hypertension or familial pulmonary arterial hypertension who completed FUTURE 1 study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Long-term, Safety, and Tolerability Extension Study Using the Pediatric Formulation of Bosentan in the Treatment of Children With Idiopathic or Familial Pulmonary Arterial Hypertension Who Completed FUTURE 1
Actual Study Start Date
:
Aug 23, 2005
Actual Primary Completion Date
:
Oct 28, 2011
Actual Study Completion Date
:
Oct 28, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bosentan Bosentan was administered at 4 mg/kg twice daily (b.i.d.) until the end of the study. It could be down-titrated to 2 mg/kg b.i.d. if not well tolerated. |
Drug: Bosentan
32-mg dispersible and breakable tablet. The body weight-adjusted dose of the dispersible tablet was dispersed in a teaspoon of water (not mixed with food) before being administered orally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to End of Study (EOS) in Height for Age. [From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average]
In order to compare the growth data with those of healthy children, growth curves are calculated from height data collected throughout the follow-up period. For each patient, height measured at each study visit was converted to a z-score and expressed in standard deviations (SD) from WHO growth standards. The Z-score was calculated according to the following formula: Z-score = (observed value of the study participant - median value of the reference population) / SD value of the reference population
- Change From Baseline to End of Study (EOS) in Body Weight [From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including growth as measured by changes from baseline in body weight and height.
- Change From Baseline to End of Study (EOS) in Systolic Blood Pressure (SBP) [From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure.
- Change From Baseline to End of Study (EOS) in Diastolic Blood Pressure (DBP) [From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure.
- Change From Baseline to End of Study (EOS) in Pulse Rate [From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in pulse rate.
- Proportion of Patients With Treatment-emergent Liver Function Abnormalities [After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including laboratory abnormalities related to liver enzymes. Proportion of patients with increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above 3 times upper limit of normal (ULN) is reported here.
- Proportion of Patients With Treatment-emergent Hemoglobin Abnormalities [After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average]
The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including hemoglobin abnormalities. Proportion of patients with marked hemoglobin decreases (i.e., decrease of or above 15% of the lower normal limit (LL)) is reported here.
- Number of Subjects With Adverse Events Leading to Premature Discontinuation of Study Treatment [From the first study drug administration in FUTURE 1, for an average of 31 months]
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 11 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Signed informed consent by the parents or the legal representatives.
-
Patients who completed the FUTURE 1 study.
-
Patients who tolerated bosentan pediatric formulation and for whom bosentan is considered beneficial at the end of FUTURE 1.
-
Males or females >= 2 and < 12 years of age at enrollment in FUTURE 2 (this study). Females who are menstruating must have a negative pregnancy test. A reliable method of contraception must be considered, if appropriate.
Exclusion Criteria:
-
Intolerance to bosentan despite dose reductions.
-
Any clinically significant laboratory abnormality that precludes continuation of bosentan therapy.
-
Pregnancy or breast-feeding.
-
Known hypersensitivity to bosentan or any of the excipients.
-
Premature and permanent study drug discontinuation during FUTURE 1.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital Cardiac Care Center | Denver | Colorado | United States | 80218 |
| 2 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 3 | Hopital Antoine Beclere | Clamart | France | 92140 | |
| 4 | Hopital Necker | Paris | France | 75743 | |
| 5 | CHE de Toulouse Hopital d'Enfants | Toulouse | France | ||
| 6 | Deutsches Herzzentrum | Berlin | Germany | ||
| 7 | Universitats Kinderklinik | Giessen | Germany | ||
| 8 | Policlinico S. Orsola-Malpighi | Bologna | Italy | 40138 | |
| 9 | Beatrix Children's Hospital | Groningen | Netherlands | ||
| 10 | Hopital des Enfants | Geneva | Switzerland | ||
| 11 | The Institute of Child Health | London | United Kingdom |
Sponsors and Collaborators
- Actelion
Investigators
- Study Director: Andjela Kusic-Pajic, MD, Actelion
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Actelion
ClinicalTrials.gov Identifier:
NCT00319020
Other Study ID Numbers:
- AC-052-367
- 2005-001967-70
First Posted:
Apr 27, 2006
Last Update Posted:
Jun 14, 2017
Last Verified:
May 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Actelion
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 36 Children ( >= 2 years and < 12 years) with idiopathic or familial pulmonary arterial hypertension were recruited from 11 centers across Europe and USA and enrolled in the FUTURE 1 trial (baseline). Only patients who completed FUTURE 1 (n=34) could be enrolled in FUTURE 2. Enrollment in FUTURE 2 started August 23, 2005. |
|---|---|
| Pre-assignment Detail | The actual number of patients enrolled in FUTURE 2 (F-2) was 33 because 2 patients did not complete FUTURE 1 (F-1) and one patient completed F-1 but was not enrolled in F-2. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients |
|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablets) during FUTURE 1 and FUTURE 2 (initiatied at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablets) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. |
| Period Title: Overall Study | ||
| STARTED | 15 | 21 |
| Enrollment in FUTURE 2 (F-2) | 13 | 20 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 7 | 13 |
Baseline Characteristics
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablets) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablets) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | Total of all reporting groups |
| Overall Participants | 15 | 21 | 36 |
| Age (Years) [Median (Full Range) ] | |||
| Median (Full Range) [Years] |
7
|
7
|
7
|
| Age, Customized (Number) [Number] | |||
| 2-3 years old |
1
6.7%
|
3
14.3%
|
4
11.1%
|
| 4-5 years old |
3
20%
|
6
28.6%
|
9
25%
|
| 6-11 years old |
11
73.3%
|
12
57.1%
|
23
63.9%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
5
33.3%
|
10
47.6%
|
15
41.7%
|
| Male |
10
66.7%
|
11
52.4%
|
21
58.3%
|
| Etiology of pulmonary arterial hypertension (PAH) (Number) [Number] | |||
| Idiopathic PAH |
12
80%
|
19
90.5%
|
31
86.1%
|
| Familial PAH |
3
20%
|
2
9.5%
|
5
13.9%
|
| Duration of pulmonary arterial hypertension (PAH) (Months) [Median (Full Range) ] | |||
| Median (Full Range) [Months] |
37.6
|
14
|
25.8
|
Outcome Measures
| Title | Change From Baseline to End of Study (EOS) in Height for Age. |
|---|---|
| Description | In order to compare the growth data with those of healthy children, growth curves are calculated from height data collected throughout the follow-up period. For each patient, height measured at each study visit was converted to a z-score and expressed in standard deviations (SD) from WHO growth standards. The Z-score was calculated according to the following formula: Z-score = (observed value of the study participant - median value of the reference population) / SD value of the reference population |
| Time Frame | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 10 | 14 | 24 |
| Z-score at baseline |
-0.8
|
0.32
|
-0.64
|
| Z-score at EOS |
-0.74
|
-0.08
|
-0.36
|
| Z-score change from baseline to EOS |
-0.05
|
-0.01
|
-0.01
|
| Title | Change From Baseline to End of Study (EOS) in Body Weight |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including growth as measured by changes from baseline in body weight and height. |
| Time Frame | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 10 | 14 | 24 |
| Weight at baseline |
19.6
|
21.6
|
19.6
|
| Weight change from baseline to EOS |
8.2
|
8.5
|
8.3
|
| Title | Change From Baseline to End of Study (EOS) in Systolic Blood Pressure (SBP) |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure. |
| Time Frame | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 10 | 14 | 24 |
| SBP at baseline |
101.5
|
104
|
102.5
|
| SBP change from baseline to EOS |
-10.5
|
4
|
-4.5
|
| Title | Change From Baseline to End of Study (EOS) in Diastolic Blood Pressure (DBP) |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in blood pressure. |
| Time Frame | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 10 | 13 | 23 |
| DBP at baseline |
54.5
|
60
|
59
|
| DBP change from baseline to EOS |
-5
|
-2
|
-3
|
| Title | Change From Baseline to End of Study (EOS) in Pulse Rate |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including changes from baseline in pulse rate. |
| Time Frame | From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 11 | 14 | 25 |
| Pulse rate at baseline |
87
|
94.5
|
88
|
| Pulse rate change from baseline to EOS |
-11
|
-10
|
-11
|
| Title | Proportion of Patients With Treatment-emergent Liver Function Abnormalities |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including laboratory abnormalities related to liver enzymes. Proportion of patients with increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above 3 times upper limit of normal (ULN) is reported here. |
| Time Frame | After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 15 | 21 | 36 |
| ALT > 3 x ULN |
0
0%
|
4.8
22.9%
|
2.8
7.8%
|
| AST > 3 x ULN |
0
0%
|
4.8
22.9%
|
2.8
7.8%
|
| Title | Proportion of Patients With Treatment-emergent Hemoglobin Abnormalities |
|---|---|
| Description | The main study objective was to assess the long-term safety and tolerability of bosentan in children with PAH, including hemoglobin abnormalities. Proportion of patients with marked hemoglobin decreases (i.e., decrease of or above 15% of the lower normal limit (LL)) is reported here. |
| Time Frame | After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-treated analysis set (all patients who received at least one dose of study drug in the combined FUTURE 1 / FUTURE 2 trial periods). Missing or incomplete data were treated as missing. |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 15 | 21 | 36 |
| Number [Percentage of participants] |
13.3
88.7%
|
9.5
45.2%
|
11.1
30.8%
|
| Title | Number of Subjects With Adverse Events Leading to Premature Discontinuation of Study Treatment |
|---|---|
| Description | |
| Time Frame | From the first study drug administration in FUTURE 1, for an average of 31 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Patients With Previous Bosentan | Bosentan-naive Patients | Total |
|---|---|---|---|
| Arm/Group Description | This group included patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 (initiation at 2 mg/kg b.i.d. for 4 weeks, then up-titrated to the maintenance dose of 4 mg/kg b.i.d. for the next 8 weeks of the FUTURE 1 trial (AC-052- 365) and to be continued in FUTURE 2. The dose could be down-titrated to 2 mg/kg b.i.d. if not tolerated). | This group included patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan (dispersible tablet) during FUTURE 1 and FUTURE 2 according to the same dosing regimen as described for "Patients with previous bosentan". Note: In this single arm trial, data are presented according to whether patients received bosentan or not before enrollment in FUTURE 1 but all the subjects received the study drug according to the same regimen. | All patients (bosentan-naive patients and patients treated with film-coated bosentan tablets before enrollment) who received at least one dose of study drug (bosentan dispersible tablets) in the combined FUTURE 1 / FUTURE 2 trial periods. |
| Measure Participants | 15 | 21 | 36 |
| Number [Participants] |
1
6.7%
|
5
23.8%
|
6
16.7%
|
Adverse Events
| Time Frame | From the first administration of study treatment and for an average of 31 months for frequent adverse events (up to 1 day after study treatment discontinuation), and for an average of 32 months (up to 28 days after study treatment discontinuation) for serious adverse events | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Patients With Previous Bosentan | Bosentan_naive Patients | Single Arm Bosentan_Total | |||
| Arm/Group Description | Patients who already received bosentan (film-coated tablets) before enrollment in FUTURE 1, and then received the pediatric formulation of bosentan during FUTURE 1 / FUTURE 2 | Patients who were not treated with bosentan before enrollment in FUTURE 1, and received the pediatric formulation of bosentan during FUTURE 1 / FUTURE 2 | All patients included in Future 1 / FUTURE 2 whether they received bosentan or not bosentan before enrollment in FUTURE 1 | |||
All Cause Mortality |
||||||
| Patients With Previous Bosentan | Bosentan_naive Patients | Single Arm Bosentan_Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Patients With Previous Bosentan | Bosentan_naive Patients | Single Arm Bosentan_Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/15 (60%) | 9/21 (42.9%) | 18/36 (50%) | |||
| Blood and lymphatic system disorders | ||||||
| IRON DEFICIENCY ANAEMIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Cardiac disorders | ||||||
| CARDIAC FAILURE | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| PERICARDIAL EFFUSION | 1/15 (6.7%) | 2 | 0/21 (0%) | 0 | 1/36 (2.8%) | 2 |
| RIGHT VENTRICULAR FAILURE | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| General disorders | ||||||
| CHEST PAIN | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| FATIGUE | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| INJECTION SITE NODULE | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| MEDICAL DEVICE COMPLICATION | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| Hepatobiliary disorders | ||||||
| AUTOIMMUNE HEPATITIS | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| Infections and infestations | ||||||
| BACTERAEMIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| BRONCHITIS VIRAL | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| CATHETER SITE INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| CELLULITIS | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| DEVICE RELATED INFECTION | 1/15 (6.7%) | 1 | 2/21 (9.5%) | 6 | 3/36 (8.3%) | 7 |
| EAR INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| LOBAR PNEUMONIA | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| LUNG INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| PNEUMONIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| PNEUMONIA VIRAL | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| VIRAL INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| VIRAL RHINITIS | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| Investigations | ||||||
| ARTERIAL CATHETERISATION | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| CATHETERISATION CARDIAC | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| HAEMOGLOBIN DECREASED | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| PULMONARY ARTERIAL PRESSURE | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| FLANK PAIN | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Nervous system disorders | ||||||
| CONVULSION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| DYSTONIA | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| SYNCOPE | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| BRONCHIAL OBSTRUCTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| COUGH | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| DIAPHRAGMATIC HERNIA | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| PULMONARY ARTERIAL HYPERTENSION | 2/15 (13.3%) | 3 | 1/21 (4.8%) | 1 | 3/36 (8.3%) | 4 |
| PULMONARY HYPERTENSION | 1/15 (6.7%) | 1 | 2/21 (9.5%) | 2 | 3/36 (8.3%) | 3 |
| PULMONARY VEIN STENOSIS | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| RESPIRATORY FAILURE | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| WHEEZING | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Surgical and medical procedures | ||||||
| ADENOIDECTOMY | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| BALLOON ATRIAL SEPTOSTOMY | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
| SYSTEMIC-PULMONARY ARTERY SHUNT | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| Vascular disorders | ||||||
| HYPERTENSION | 0/15 (0%) | 0 | 1/21 (4.8%) | 1 | 1/36 (2.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Patients With Previous Bosentan | Bosentan_naive Patients | Single Arm Bosentan_Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/15 (80%) | 16/21 (76.2%) | 26/36 (72.2%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Cardiac disorders | ||||||
| CYANOSIS | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| PALPITATIONS | 0/15 (0%) | 0 | 2/21 (9.5%) | 4 | 2/36 (5.6%) | 4 |
| Ear and labyrinth disorders | ||||||
| EAR PAIN | 0/15 (0%) | 0 | 2/21 (9.5%) | 3 | 2/36 (5.6%) | 3 |
| Eye disorders | ||||||
| PHOTOPHOBIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| VISION BLURRED | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 1/15 (6.7%) | 1 | 5/21 (23.8%) | 6 | 6/36 (16.7%) | 7 |
| ABDOMINAL PAIN UPPER | 0/15 (0%) | 0 | 3/21 (14.3%) | 4 | 3/36 (8.3%) | 4 |
| CONSTIPATION | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| DIARRHOEA | 2/15 (13.3%) | 2 | 1/21 (4.8%) | 1 | 3/36 (8.3%) | 3 |
| NAUSEA | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| VOMITING | 0/15 (0%) | 0 | 4/21 (19%) | 4 | 4/36 (11.1%) | 4 |
| DYSPEPSIA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| TOOTH DISCOLOURATION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| General disorders | ||||||
| ADVERSE DRUG REACTION | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 2 | 2/36 (5.6%) | 3 |
| ASTHENIA | 1/15 (6.7%) | 1 | 2/21 (9.5%) | 3 | 3/36 (8.3%) | 4 |
| CHEST PAIN | 0/15 (0%) | 0 | 3/21 (14.3%) | 10 | 3/36 (8.3%) | 10 |
| FATIGUE | 0/15 (0%) | 0 | 2/21 (9.5%) | 3 | 2/36 (5.6%) | 3 |
| PYREXIA | 1/15 (6.7%) | 1 | 2/21 (9.5%) | 2 | 3/36 (8.3%) | 3 |
| CATHETER SITE PAIN | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Immune system disorders | ||||||
| ALLERGY TO PLANTS | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Infections and infestations | ||||||
| BRONCHITIS | 2/15 (13.3%) | 2 | 3/21 (14.3%) | 4 | 5/36 (13.9%) | 6 |
| H1N1 INFLUENZA | 2/15 (13.3%) | 2 | 0/21 (0%) | 0 | 2/36 (5.6%) | 2 |
| INFLUENZA | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| NASOPHARYNGITIS | 3/15 (20%) | 5 | 4/21 (19%) | 6 | 7/36 (19.4%) | 11 |
| OTITIS MEDIA | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| PHARYNGITIS | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| PNEUMONIA | 1/15 (6.7%) | 5 | 2/21 (9.5%) | 2 | 3/36 (8.3%) | 7 |
| TONSILLITIS | 1/15 (6.7%) | 2 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 3 |
| UPPER RESPIRATORY TRACT INFECTION | 1/15 (6.7%) | 1 | 4/21 (19%) | 6 | 5/36 (13.9%) | 7 |
| VIRAL INFECTION | 0/15 (0%) | 0 | 2/21 (9.5%) | 2 | 2/36 (5.6%) | 2 |
| GASTROINTESTINAL VIRAL INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| PERTUSSIS | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| URINARY TRACT INFECTION | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| CONTUSION | 0/15 (0%) | 0 | 2/21 (9.5%) | 2 | 2/36 (5.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| PAIN IN EXTREMITY | 0/15 (0%) | 0 | 2/21 (9.5%) | 2 | 2/36 (5.6%) | 2 |
| MUSCULOSKELETAL PAIN | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Nervous system disorders | ||||||
| DIZZINESS | 1/15 (6.7%) | 1 | 2/21 (9.5%) | 3 | 3/36 (8.3%) | 4 |
| HEADACHE | 1/15 (6.7%) | 1 | 3/21 (14.3%) | 6 | 4/36 (11.1%) | 7 |
| SYNCOPE | 2/15 (13.3%) | 2 | 1/21 (4.8%) | 4 | 3/36 (8.3%) | 6 |
| Psychiatric disorders | ||||||
| AGGRESSION | 0/15 (0%) | 0 | 2/21 (9.5%) | 2 | 2/36 (5.6%) | 2 |
| Renal and urinary disorders | ||||||
| ENURESIS | 0/15 (0%) | 0 | 2/21 (9.5%) | 2 | 2/36 (5.6%) | 2 |
| Reproductive system and breast disorders | ||||||
| NIPPLE SWELLING | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| COUGH | 1/15 (6.7%) | 3 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 4 |
| EPISTAXIS | 1/15 (6.7%) | 1 | 1/21 (4.8%) | 1 | 2/36 (5.6%) | 2 |
| NASAL CONGESTION | 0/15 (0%) | 0 | 3/21 (14.3%) | 4 | 3/36 (8.3%) | 4 |
| PULMONARY ARTERIAL HYPERTENSION | 3/15 (20%) | 3 | 1/21 (4.8%) | 1 | 4/36 (11.1%) | 4 |
| PULMONARY HYPERTENSION | 0/15 (0%) | 0 | 3/21 (14.3%) | 3 | 3/36 (8.3%) | 3 |
| OROPHARYNGEAL PAIN | 1/15 (6.7%) | 2 | 0/21 (0%) | 0 | 1/36 (2.8%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||
| ECZEMA | 1/15 (6.7%) | 1 | 0/21 (0%) | 0 | 1/36 (2.8%) | 1 |
| Vascular disorders | ||||||
| FLUSHING | 1/15 (6.7%) | 1 | 3/21 (14.3%) | 4 | 4/36 (11.1%) | 5 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any study-related article or abstract written independently by investigators should be submitted to Actelion for review at least 60 days prior to submission for publication or presentation.
Results Point of Contact
| Name/Title | clinical trial disclosure desk |
|---|---|
| Organization | Actelion Pharmaceuticals Ltd |
| Phone | |
| clinical-trials-disclosure@actelion.com |
Responsible Party:
Actelion
ClinicalTrials.gov Identifier:
NCT00319020
Other Study ID Numbers:
- AC-052-367
- 2005-001967-70
First Posted:
Apr 27, 2006
Last Update Posted:
Jun 14, 2017
Last Verified:
May 1, 2017