Trial · NCT01223352
Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension
NCT01223352, Phase 3, Completed, Actelion; results first posted 2017-06-29
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension. Trials, record NCT01223352. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01223352
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Effects of Two Dosing Regimens of Bosentan in Children With Pulmonary Arterial Hypertension
- NCT number
- NCT01223352
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 64 participants, actual
- Lead sponsor
- Actelion
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- bosentan
- First posted
- 2010-10-19
- Last updated
- 2025-02-04
- Results first posted
- 2017-06-29
Source ClinicalTrials.gov
Registered outcomes8
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan | 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) \[AUC(0-24c)\]. |
| Other | Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan | 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 | 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. The peak plasma concentration (Cmax) of bosentan was directly obtained from the measured plasma concentrations and was dose-corrected to the target dose of 2 mg/kg (Cmaxc). |
| Other | Time to Reach Cmax [Tmax] of Bosentan | 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 | 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. tmax was obtained directly from the measured plasma concentrations. |
| Other | Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | 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 | Concentrations of the metabolites 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. Daily exposure to the metabolites corresponds to the area under the concentration-time curve \[AUC(0-24)\] of the corresponding metabolite over a period of 24 hours, and was calculated in the same manner as the primary endpoint. AUC(0-24c) was corrected to 2 mg/kg (target dose) \[AUC(0-24c)\]. |
| Other | Change From Baseline in WHO Functional Class at End of Study | Baseline, up to Week 24 on average | The World Health Organization (WHO) defines 4 classes to classify the functional status of patients with pulmonary hypertension (PH): Class I (FC I): No limitation of physical activity. Class II (FC II): Slight limitation of physical activity. Class IIII (FC III): Marked limitation of physical activity. Class IV (FC IV): Inability to carry out any physical activity without symptoms. Number of patients with improvement (shift from a higher to a lower class), worsening (shift from a lower to a higher class) or no change in WHO functional class at end of study compared to baseline are determined. |
| Other | Change From Baseline in Global Clincial Impression Scale (GCIS) at End of Study | Baseline, up to Week 24 on average | The GCIS is an assessment tool providing a single global assessment of the patient's current overall clinical condition: Very Good, Good, Neither Good or Bad, Bad and Very Bad. The assessment was performed both by the physician and the parents / legal representatives independently. Global clinical impression (GCI) at end of study was compared to GCI at baseline and the number of patients with clinical condition considered as worsened, improved or unchanged are determined. |
| Other | Number of Patients With Treatment-emergent Liver Function Abnormalities | Baseline, up to Week 24 | Number of patients with increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) above 3 times upper limit of normal (ULN). The worst post-baseline value was considered. The treatment-emergent period was defined as study treatment start date up to 7 calendar days after study treatment end date. |
| Other | Number of Patients With Treatment-emergent Hemoglobin Abnormalities | Baseline, up to Week 24 | Number of patients with marked hemoglobin decreases (absolute values below 10 g/dL). The worst post-baseline value was considered. The treatment-emergent period was defined as study treatment start date up to 7 calendar days after study treatment end date. |
Source ClinicalTrials.gov
Outcomes8
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan | 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 | 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. | h*ng/mL | GEOMETRIC_MEAN |
| OTHER_PRE_SPECIFIED | Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan | 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 | 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. | ng/mL | GEOMETRIC_MEAN |
| OTHER_PRE_SPECIFIED | Time to Reach Cmax [Tmax] of Bosentan | 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 | 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. | hours | MEDIAN |
| OTHER_PRE_SPECIFIED | Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | 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 | 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. | h*ng/mL | GEOMETRIC_MEAN |
| OTHER_PRE_SPECIFIED | Change From Baseline in WHO Functional Class at End of Study | Baseline, up to Week 24 on average | All-randomized set. Because all 64 randomized patients were treated with at least one dose of study drug, the All-randomized set was identical to the All-treated set. | Participants | NUMBER |
| OTHER_PRE_SPECIFIED | Change From Baseline in Global Clincial Impression Scale (GCIS) at End of Study | Baseline, up to Week 24 on average | All-randomized set. Because all 64 randomized patients were treated with at least one dose of study drug, the All-randomized set was identical to the All-treated set. | Participants | NUMBER |
| OTHER_PRE_SPECIFIED | Number of Patients With Treatment-emergent Liver Function Abnormalities | Baseline, up to Week 24 | All randomized patients who received at least one dose of study drug and with available data. | Participants | NUMBER |
| OTHER_PRE_SPECIFIED | Number of Patients With Treatment-emergent Hemoglobin Abnormalities | Baseline, up to Week 24 | All randomized patients who received at least one dose of study drug and with available data. | Participants | NUMBER |
Source ClinicalTrials.gov
Results by group38
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan | Bosentan 2 mg/kg t.i.d. (PK Set) | 7275.1 | 95% Confidence Interval 5468.2 to 9679.0 | h*ng/mL | |
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan | Bosentan 2 mg/kg b.i.d. (PK Set) | 8535.4 | 95% Confidence Interval 6936.0 to 10503.7 | h*ng/mL | |
| Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan | Bosentan 2 mg/kg t.i.d. (PK Set) | 527.9 | 95% Confidence Interval 386.0 to 721.9 | ng/mL | |
| Dose-corrected Maximum Plasma Concentration [Cmaxc] of Bosentan | Bosentan 2 mg/kg b.i.d. (PK Set) | 742.8 | 95% Confidence Interval 572.8 to 963.2 | ng/mL | |
| Time to Reach Cmax [Tmax] of Bosentan | Bosentan 2 mg/kg t.i.d. (PK Set) | 3 | Full Range 1 to 8 | hours | |
| Time to Reach Cmax [Tmax] of Bosentan | Bosentan 2 mg/kg b.i.d. (PK Set) | 3 | Full Range 0 to 7.5 | hours | |
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | Bosentan 2 mg/kg t.i.d. (PK Set) | AUC(0-24C) for Ro 478634 | 173.2 | 95% Confidence Interval 126.2 to 237.6 | h*ng/mL |
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | Bosentan 2 mg/kg b.i.d. (PK Set) | AUC(0-24C) for Ro 478634 | 200.4 | 95% Confidence Interval 152.2 to 263.9 | h*ng/mL |
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | Bosentan 2 mg/kg t.i.d. (PK Set) | AUC(0-24C) for Ro 485033 | 968.8 | 95% Confidence Interval 723.3 to 1297.7 | h*ng/mL |
| Dose-corrected Daily Exposure [AUC(0-24c)] to Bosentan Metabolites (Ro 478634, Ro 485033, Ro 641056) | Bosentan 2 mg/kg b.i.d. (PK Set) | AUC(0-24C) for Ro 485033 | 1352.5 | 95% Confidence Interval 1073.4 to 1704.0 | h*ng/mL |
1 to 10 of 38Source ClinicalTrials.gov
See all 38 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Bosentan 2 mg/kg t.i.d. | 31 | |
| Overall Study | STARTED | Bosentan 2 mg/kg b.i.d. | 33 | |
| Overall Study | COMPLETED | Bosentan 2 mg/kg t.i.d. | 31 | |
| Overall Study | COMPLETED | Bosentan 2 mg/kg b.i.d. | 33 | |
| Overall Study | NOT COMPLETED | Bosentan 2 mg/kg t.i.d. | 0 | |
| Overall Study | NOT COMPLETED | Bosentan 2 mg/kg b.i.d. | 0 |
Source ClinicalTrials.gov
Adverse events64
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | BRONCHITIS | Infections and infestations | Bosentan 2 mg/kg t.i.d | 1 | 31 | 1 |
| other | BRONCHITIS | Infections and infestations | Bosentan 2 mg/kg b.i.d | 2 | 33 | 2 |
| other | CONSTIPATION | Gastrointestinal disorders | Bosentan 2 mg/kg t.i.d | 2 | 31 | 2 |
| other | CONSTIPATION | Gastrointestinal disorders | Bosentan 2 mg/kg b.i.d | 1 | 33 | 1 |
| other | COUGH | Respiratory, thoracic and mediastinal disorders | Bosentan 2 mg/kg t.i.d | 3 | 31 | 3 |
| other | COUGH | Respiratory, thoracic and mediastinal disorders | Bosentan 2 mg/kg b.i.d | 0 | 33 | 0 |
| other | DIARRHOEA | Gastrointestinal disorders | Bosentan 2 mg/kg t.i.d | 4 | 31 | 5 |
| other | DIARRHOEA | Gastrointestinal disorders | Bosentan 2 mg/kg b.i.d | 2 | 33 | 2 |
| other | EPISTAXIS | Respiratory, thoracic and mediastinal disorders | Bosentan 2 mg/kg t.i.d | 3 | 31 | 3 |
| other | EPISTAXIS | Respiratory, thoracic and mediastinal disorders | Bosentan 2 mg/kg b.i.d | 0 | 33 | 0 |
1 to 10 of 64Source ClinicalTrials.gov
See all 64 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Bosentan 2 mg/kg t.i.d | ||
| Total, all-cause mortality | Bosentan 2 mg/kg b.i.d | ||
| Total, other adverse events | Bosentan 2 mg/kg t.i.d | 18 | 31 |
| Total, other adverse events | Bosentan 2 mg/kg b.i.d | 18 | 33 |
| Total, serious adverse events | Bosentan 2 mg/kg t.i.d | 6 | 31 |
| Total, serious adverse events | Bosentan 2 mg/kg b.i.d | 4 | 33 |
Source ClinicalTrials.gov
Papers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons1
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison |
|---|
| Bosentan 2 mg/kg t.i.d vs Bosentan 2 mg/kg b.i.d: serious adverse events |
Source Trial comparisons
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01223352
GET https://conductscience.org/api/trials/v1/NCT01223352/results?page=2