Pulmonary Arterial HypertensionPhase 3FUTURE 3NCT01223352

Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension

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 primary objective of AC-052-373 was to assess the pharmacokinetic (PK) profile of two dosing regimens of the pediatric formulation of bosentan in children with pulmonary arterial hypertension (PAH) <12 years of age. Read more about this study

Who is it for?: Ages 3 months to 12 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: 64 participants
Where: No sites listed yet
Study dates: 8 Mar 2011to 19 Aug 2013
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 3 months to 12 years
All sexes
No healthy volunteers
Child

Who may be able to join

PAH diagnosis confirmed with right heart catheterization (RHC):
Idiopathic or heritable PAH, or
Associated PAH persisting after complete repair of a congenital heart defect (PAH has to be persistent for at least 6 months after surgery) or
PAH-Congenital Heart Disease (PAH-CHD) associated with systemic-to-pulmonary shunts (after global amendment dated 09 May 2012)
World Health Organization functional Class (WHO FC) I, II or III
Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)

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Body weight ≥ 3.5 kg
Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)
Baseline PAH-therapy (Calcium channel blocker, bosentan, prostanoid, phosphodiesterase type-5 inhibitor) if present, has to be stable for at least 3 months prior to screening. During the study, all background treatments should remain stable
Signed informed consent by the parents or legal representatives

Who cannot join

PAH etiologies other than listed above
Non-stable disease status
Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
Systolic blood pressure < 80% of the lower limit of normal range
Aspartate aminotransferase and/or alanine aminotransferase values > 1.5 times the upper limit of normal range.
Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C

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Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal range.
Known intolerance or hypersensitivity to bosentan or any of the excipients of the dispersible Tracleer tablet
Treatment with forbidden medication within 2 weeks or at least 5 times the half-life prior to randomization, whichever is the longest:
Glibenclamide (glyburide)
Cyclosporin A
Sirolimus
Tacrolimus
Fluconazole
Rifampicin (rifampin)
Ritonavir
Co-administration of CYP2C9 inhibitors (e.g., amiodarone, voriconazole) and moderate/strong CYP3A4 inhibitors (e.g., amprenavir, erythromycin, ketoconazole, diltiazem, itraconazole)
Endothelin receptor antagonists (ERAs) other than bosentan
Treatment with another investigational drug within 1 month prior to randomization or planned treatment

About this study

Official title: An Open-label, Prospective Multicenter Study to Assess the Pharmacokinetics, Tolerability, Safety and Efficacy of the Pediatric Formulation of Bosentan Two Versus Three Times a Day in Children With Pulmonary Arterial Hypertension

Conditions: Pulmonary Arterial Hypertension
Being tested: bosentan
Keywords: pulmonary arterial hypertension, children, pediatric, bosentan
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 Tracleer, ACT-050088
32 mg quadrisected dispersible tablet. The dosage of bosentan (2 mg/Kg) was adjusted according to the patient's body weight at initiation of the study treatment. Dosage readjustment was permitted after 12 weeks of treatment.

Study groups in NCT01223352
Study group	Role	What they receive
Bosentan 2 mg/Kg t.i.d.	Experimental	2 mg/kg bosentan administered three times a day (morning, afternoon, evening) for a planned duration of 24 weeks Receives: Drug: bosentan
Bosentan 2 mg/Kg b.i.d.	Experimental	2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks Receives: Drug: bosentan

What is being measured

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

Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan
Daily exposure was measured by the area under the plasma concentration-time curve over a period of 24 hours [AUC(0-24)].
Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. AUC(0-24) was calculated as a multiple of AUCtau, which is the AUC over a dosing interval (AUCtau x 2 for the b.i.d. dosing regimen and AUCtau x 3 for the t.i.d. regimen). As the smallest dose unit was 8 mg (1/4 tablet), it was not possible to achieve the exact target dose of 2 mg/kg. Therefore, AUC(0-24) was corrected to 2 mg/kg (target dose) [AUC(0-24c)].
Measured: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment

Timeline

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

8 Mar 201119 Aug 2013

First posted19 Oct 2010 (estimated)
Study start8 Mar 2011
Primary completion3 Apr 2013
Study completion19 Aug 2013

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.
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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01223352
Sponsor's protocol ID: AC-052-373
Acronym: FUTURE 3
Status last verified: Jan 2025
First submitted: 12 Oct 2010
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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

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
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
RecruitingPhase 4
A Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (PAH) in India (MK-7962-037)
Pulmonary Arterial Hypertension
RecruitingPhase 2/3
The Effect of Additive On-Demand Sildenafil vs. Dextrose Candy on Maximum Exercise Capacity in Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
Recruiting
Rehabilitation Program for People With Methamphetamine-Associated Cardiopulmonary Conditions
Methamphetamine-Associated Heart Failure, Methamphetamine-Associated Pulmonary Arterial Hypertension

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, Prospective Multicenter Study to Assess the Pharmacokinetics, Tolerability, Safety and Efficacy of the Pediatric Formulation of Bosentan Two Versus Three Times a Day in Children With Pulmonary Arterial Hypertension
ClinicalTrials.gov ID: NCT01223352
Acronym / sponsor ID: FUTURE 3 / AC-052-373
Conditions: Pulmonary Arterial Hypertension
Keywords: pulmonary arterial hypertension, children, pediatric, bosentan
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: 8 Mar 2011 (actual)
Primary completion: 3 Apr 2013 (actual)
Study completion: 19 Aug 2013 (actual)
First posted: 19 Oct 2010 (estimated)
Results: Posted 29 Jun 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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Bosentan 2 mg/Kg t.i.d.	Experimental	Drug: bosentan2 mg/kg bosentan administered three times a day (morning, afternoon, evening) for a planned duration of 24 weeks
Bosentan 2 mg/Kg b.i.d.	Experimental	Drug: bosentan2 mg/kg bosentan administered twice daily (morning and evening) for a planned duration of 24 weeks

Who may qualify

Ages: 3 months to 12 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (10 listed)

PAH diagnosis confirmed with right heart catheterization (RHC):
World Health Organization functional Class (WHO FC) I, II or III
Male or female ≥ 3 months and < 12 years of age (maximum age at randomization is 11.5 years)
Body weight ≥ 3.5 kg
Peripheral oxygen saturation (SpO2) ≥ 88% (at rest, on room air)

Key exclusion criteria (19 listed)

PAH etiologies other than listed above
Non-stable disease status
Need or plan to wean patient from intravenous epoprostenol or intravenous or inhaled iloprost
Systolic blood pressure < 80% of the lower limit of normal range
Aspartate aminotransferase and/or alanine aminotransferase values > 1.5 times the upper limit of normal range.

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: Tracleer, ACT-05008832 mg quadrisected dispersible tablet. The dosage of bosentan (2 mg/Kg) was adjusted according to the patient's body weight at initiation of the study treatment. Dosage readjustment was permitted after 12 weeks of treatment.	Drug	Bosentan 2 mg/Kg b.i.d., Bosentan 2 mg/Kg t.i.d.

Primary outcome

Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan
Time frame: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment
Daily exposure was measured by the area under the plasma concentration-time curve over a period of 24 hours [AUC(0-24)]. Concentrations of bosentan were measured directly in blood samples collected prior to study drug administration and up to 8 hours or up to 12 hours post-dose for the t.i.d and b.i.d. dosing regimen, respectively. AUC(0-24) was calculated as a multiple of AUCtau, which is the AUC over a dosing interval (AUCtau x 2 for the b.i.d. dosing regimen and AUCtau x 3 for the t.i.d. regimen). As the smallest dose unit was 8 mg (1/4 tablet), it was not possible to achieve the exact target dose of 2 mg/kg. Therefore, AUC(0-24) was corrected to 2 mg/kg (target dose) [AUC(0-24c)].

Results and safety

Results posted to the registry on 29 Jun 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
Bosentan 2 mg/kg t.i.d.	31	31
Bosentan 2 mg/kg b.i.d.	33	33

Primary outcome: Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan

Time frame: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment. Geometric mean (95% Confidence Interval). Unit: h*ng/mL

Measure	Bosentan 2 mg/kg t.i.d. (PK Set) n = 27	Bosentan 2 mg/kg b.i.d. (PK Set) n = 31
Value	7275.1 (5468.2 to 9679.0)	8535.4 (6936.0 to 10503.7)

Bosentan 2 mg/kg t.i.d. (PK Set) vs Bosentan 2 mg/kg b.i.d. (PK Set): Ratio of geometric means: 0.85 (95% CI 0.61 to 1.20)

Population analysed: Per-protocol PK analysis set (PK set): All patients included in the bosentan 2 mg/kg b.i.d. and bosentan 2 mg/kg t.i.d. groups who received at least one dose of bosentan and who were able to provide at least 5 blood samples for PK assessments and who did not violate the protocol in a way that might affect the evaluation of the PK main endpoint.

Adverse events

Time frame: From the first dose of study treatment on Day 1 up to 7 days after treatment discontinuation, i.e. up to Week 25 on average. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bosentan 2 mg/kg t.i.d	6 of 31 (19.4%)	18 of 31 (58.1%)	Not reported
Bosentan 2 mg/kg b.i.d	4 of 33 (12.1%)	18 of 33 (54.5%)	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.

Related trials for Pulmonary Arterial Hypertension

Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
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RecruitingPhase 4
A Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (PAH) in India (MK-7962-037)
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RecruitingPhase 2/3
The Effect of Additive On-Demand Sildenafil vs. Dextrose Candy on Maximum Exercise Capacity in Pulmonary Arterial Hypertension
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Rehabilitation Program for People With Methamphetamine-Associated Cardiopulmonary Conditions
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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 10 inclusion and 19 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 Jun 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?

Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan (time frame: 0, 0.5, 1, 3, 5 (or 7.5), 8 (or 12 hours) post-dose at Week 4, after at least 2 weeks of stable study drug treatment). 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 NCT01223352.

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; AzTrials last refreshed its copy on 8 Nov 2026.