Pulmonary Arterial HypertensionPhase 3FUTURE 2NCT00319020

Bosentan in Children With Pulmonary Arterial Hypertension Extension Study

A Phase 3 study testing Bosentan in people with Pulmonary Arterial Hypertension, run by Actelion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 2 to 11 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: Bosentan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: No sites listed yet
Study dates: 23 Aug 2005to 28 Oct 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 11 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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.

About this study

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

Conditions: Pulmonary Arterial Hypertension
Being tested: Bosentan
Keywords: bosentan, pulmonary arterial hypertension, children, FUTURE 1
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BosentanDrug
Also called Ro 47-0203, Tracleer
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

Study groups in NCT00319020
Study group	Role	What they receive
Bosentan	Experimental	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. Receives: Drug: Bosentan

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline to End of Study (EOS) in Height for Age.
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
Measured: From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average
Change From Baseline to End of Study (EOS) in Body Weight
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.
Measured: From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average
Change From Baseline to End of Study (EOS) in Systolic Blood Pressure (SBP)
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.
Measured: From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average
Change From Baseline to End of Study (EOS) in Diastolic Blood Pressure (DBP)
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.
Measured: From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average
Change From Baseline to End of Study (EOS) in Pulse Rate
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.
Measured: From baseline (FUTURE 1) up to 28 days after study treatment discontinuation (EOS or premature study treatment discontinuation), i.e. 32 months in average
Proportion of Patients With Treatment-emergent Liver Function Abnormalities
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.
Measured: After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average
Proportion of Patients With Treatment-emergent Hemoglobin Abnormalities
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.
Measured: After baseline, up to 1 calendar day after study treatment discontinuation in FUTURE 1 or FUTURE 2, i.e. 31 months in average
Number of Subjects With Adverse Events Leading to Premature Discontinuation of Study Treatment
Measured: From the first study drug administration in FUTURE 1, for an average of 31 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Aug 200528 Oct 2011

First posted27 Apr 2006 (estimated)
Study start23 Aug 2005
Primary completion28 Oct 2011
Study completion28 Oct 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00319020
Sponsor's protocol ID: AC-052-367
Other IDs: 2005-001967-70, 2005
Acronym: FUTURE 2
Status last verified: Jan 2025
First submitted: 26 Apr 2006
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Berger RM, Haworth SG, Bonnet D, Dulac Y, Fraisse A, Galie N, Ivy DD, Jais X, Miera O, Rosenzweig EB, Efficace M, Kusic-Pajic A, Beghetti M. FUTURE-2: Results from an open-label, long-term safety and tolerability extension study using the pediatric FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion. Int J Cardiol. 2016 Jan 1;202:52-8. doi: 10.1016/j.ijcard.2015.08.080. Epub 2015 Aug 9.
PubMed 26386921

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00319020
Acronym / sponsor ID: FUTURE 2 / AC-052-367
Conditions: Pulmonary Arterial Hypertension
Keywords: bosentan, pulmonary arterial hypertension, children, FUTURE 1
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: 23 Aug 2005 (actual)
Primary completion: 28 Oct 2011 (actual)
Study completion: 28 Oct 2011 (actual)
First posted: 27 Apr 2006 (estimated)
Results: Posted 29 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Bosentan	Experimental	Drug: BosentanBosentan 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.

Who may qualify

Ages: 2 to 11 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BosentanAlso: Ro 47-0203, Tracleer32-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	Drug	Bosentan

Primary outcome

Change From Baseline to End of Study (EOS) in Height for Age.
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
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
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
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)
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
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)
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
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
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
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
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
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
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
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
Time frame: From the first study drug administration in FUTURE 1, for an average of 31 months

Results and safety

Results posted to the registry on 29 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Patients With Previous Bosentan	15	8
Bosentan-naive Patients	21	8

Primary outcome: Change From Baseline to End of Study (EOS) in Height for Age.

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. Median (Full Range). Unit: Z-score

Measure	Patients With Previous Bosentan n = 10	Bosentan-naive Patients n = 14	Total n = 24
Z-score at baseline	-0.8 (-3.32 to 3.72)	0.32 (-2.62 to 1.99)	-0.64 (-3.32 to 3.72)
Z-score at EOS	-0.74 (-3.52 to 2.78)	-0.08 (-2.44 to 1.84)	-0.36 (-3.52 to 2.78)
Z-score change from baseline to EOS	-0.05 (-0.94 to 0.91)	-0.01 (-0.77 to 1.08)	-0.01 (-0.94 to 1.08)

Population analysed: 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.

Primary outcome: Change From Baseline to End of Study (EOS) in Body Weight

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. Median (Full Range). Unit: kg

Measure	Patients With Previous Bosentan n = 10	Bosentan-naive Patients n = 14	Total n = 24
Weight at baseline	19.6 (12.5 to 30.2)	21.6 (11 to 39)	19.6 (11 to 39)
Weight change from baseline to EOS	8.2 (5 to 24.8)	8.5 (1.8 to 18.5)	8.3 (1.8 to 24.8)

Primary outcome: Change From Baseline to End of Study (EOS) in Systolic Blood Pressure (SBP)

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. Median (Full Range). Unit: mmHg

Measure	Patients With Previous Bosentan n = 10	Bosentan-naive Patients n = 14	Total n = 24
SBP at baseline	101.5 (87 to 115)	104 (79 to 121)	102.5 (79 to 121)
SBP change from baseline to EOS	-10.5 (-20 to 25)	4 (-21 to 28)	-4.5 (-21 to 28)

Primary outcome: Change From Baseline to End of Study (EOS) in Diastolic Blood Pressure (DBP)

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. Median (Full Range). Unit: mmHg

Measure	Patients With Previous Bosentan n = 10	Bosentan-naive Patients n = 13	Total n = 23
DBP at baseline	54.5 (47 to 94)	60 (52 to 75)	59 (47 to 94)
DBP change from baseline to EOS	-5 (-34 to 19)	-2 (-13 to 20)	-3 (-34 to 20)

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. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Patients With Previous Bosentan	9 of 15 (60%)	12 of 15 (80%)	Not reported
Bosentan_naive Patients	9 of 21 (42.9%)	16 of 21 (76.2%)	Not reported
Single Arm Bosentan_Total	18 of 36 (50%)	26 of 36 (72.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26386921Berger RM, Haworth SG, Bonnet D, Dulac Y, Fraisse A, Galie N, Ivy DD, Jais X, Miera O, Rosenzweig EB, Efficace M, Kusic-Pajic A, Beghetti M. FUTURE-2: Results from an open-label, long-term safety and tolerability extension study using the pediatric FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion. Int J Cardiol. 2016 Jan 1;202:52-8. doi: 10.1016/j.ijcard.2015.08.080. Epub 2015 Aug 9.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andjela Kusic-Pajic, MD study director

Actelion

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bosentan in people with Pulmonary Arterial Hypertension, run by Actelion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to End of Study (EOS) in Height for Age. (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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00319020, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.