Clinical Study to Assess the Long-term Safety, Tolerability, and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Study Overview
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Brief Summary
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Long-term study to evaluate if macitentan is safe, tolerable and efficient enough to be used for treatment of Eisenmenger syndrome.

Official Title
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Long Term, Single-arm, Open-label Extension Study of Protocol AC-055-305 to Assess the Safety, Tolerability and Efficacy of Macitentan in Subjects With Eisenmenger Syndrome

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Macitentan 10 mg tablet, once daily.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with ES (including those with Down Syndrome) having completed the double-blind AC-055-305 / MAESTRO study as scheduled, i.e., who remained in the double-blind study up to Week 16 (whether or not they were still taking study drug at the end of this period). Exclusion Criteria: Subjects who prematurely discontinue double-blind study drug during the AC-055-305 / MAESTRO study due to: an AE assessed as related to the use of study drug, or elevated liver tests (related or unrelated to study drug).

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Macitentan<br>Macitentan 10 mg tablet, once daily. | Drug: Macitentan 10 mg tablet, once daily.<br>* Macitentan 10 mg tablet, once daily.<br>* Other names: ACT-064992;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Exercise Capacity as Measured by 6-minute Walking Distance (6MWD) Month 6 and 12 | NOTE: The MAESTRO-OL study was exploratory in nature and no primary efficacy and safety endpoint were defined in the clinical protocol. This and the other exploratory efficacy outcome measures posted were selected to be reported as a primary endpoints. All efficacy analyses were considered exploratory. The analyses of the exploratory efficacy endpoints focused on the absolute values and on the change from DB baseline to Week 16 in the DB study and to Month 6 and Month 12 in the OL study. For missing 6MWD values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a distance of zero (0) meters was imputed for all 6MWD visits from the date of death. For any other reasons, the last available value was carried forward. | From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study. | 
| Change in WHO Functional Class (FC) at Month 6 and 12 | Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing stairs). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. For missing WHO FC values in the OL study, the following imputation rules were applied: If the reason for missing data was death, class IV was imputed for all WHO visits from the date of death. For any other reasons, the last available value was carried forward. | From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study. | 
| Change in Borg Dyspnea Score at Month 6 and 12 | The Borg dyspnea score rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). For missing Borg dyspnea index values in the OL study, the following imputation rules were applied: If the reason for missing data was death, a value of 10 was imputed for all Borg visits from the date of death. For any other reasons, the last available value was carried forward. | From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study. | 
| Change in Peripheral Oxygen Saturation (SpO2) at Rest at Month 6 and 12 | No imputation of missing data for SpO2 was applied. Oxygen saturation assessed by pulse oximetry: peripheral oxygen saturation (SpO2) at rest before the 6-minute walk test (6MWT) | From baseline in DB parent study (AC-055-305, NCT01743001) up to month 12 in this OL study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eisenmenger Syndrome, exercise capacity