Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The main objective of the AC 055 303/SERAPHIN OL study, which will follow the AC 055 302/SERAPHIN study, will be to assess the long-term safety and tolerability of ACT 064992 in patients with symptomatic PAH.

Official Title
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Long-term Single-arm Open-label Extension Study of the SERAPHIN Study, to Assess the Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Macitentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to initiation of any study-mandated procedure. Patients with pulmonary arterial hypertension and having completed the event-driven study, AC 055 302/SERAPHIN, or Patients who have experienced a clinical worsening of PAH in AC 055 302/SERAPHIN and for whom a written approval to roll over into this study has been obtained from the Sponsor. Women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception during study treatment and for at least 28 days after study treatment termination. Exclusion Criteria: Any major violation of protocol AC 055 302/SERAPHIN. Pregnancy or breast-feeding. AST and/or ALT > 3 times the upper limit of the normal range. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results, such as drug or alcohol dependence or psychiatric disease. Known hypersensitivity to ACT 064992 or any of the excipients.

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: ACT-064992<br>ACT-064992 | Drug: Macitentan<br>* Tablet, oral administration, 10 mg dose 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 |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) up to 28 Days After Study Treatment Discontinuation | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. | Up to 28 days after study treatment discontinuation (Up to 12 years) | 
| Number of Participants With Death up to 28 Days After Study Treatment Discontinuation | Number of participants with deaths up to 28 days after study treatment discontinuation were reported. | Up to 28 days after study treatment discontinuation (Up to 12 years) | 
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) up to 28 Days After Study Treatment Discontinuation | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically significant, or requires intervention to prevent at least one of the outcomes listed above. | Up to 28 days after study treatment discontinuation (Up to 12 years) | 
| Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment | Number of participants with AEs leading to permanent discontinuation of study treatment were reported. An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Up to 28 days after study treatment discontinuation (Up to12 years) | 
| Number of Participants With Treatment Emergent Abnormal Liver Tests up to 28 Days After Study Treatment Discontinuation | Number of participants with treatment-emergent abnormal liver tests: Alanine aminotransferase (ALT) greater than (>) 3*upper limit of normal (ULN) or aspartate aminotransferase (AST) >3* ULN, ALT >5* ULN or AST >5*ULN, ALT >8*ULN or AST >8*ULN, total bilirubin (TBIL) >2*ULN, ALT >3*ULN or AST >3*ULN and TBIL >2*ULN at any time were reported. | Up to 28 days after study treatment discontinuation (Up to12 years) | 
| Number of Participants With Treatment Emergent Hemoglobin Abnormality up to 28 Days After Study Treatment Discontinuation | Number of participants with treatment-emergent hemoglobin (HGB) abnormality up to 28 days after study treatment discontinuation were reported. Participants assessed for different categories of HGB were <=80 grams/Liter (g/L), <=100g/L, decrease from baseline >=20 g/L, and decrease from baseline >=50 g/L. | Up to 28 days after treatment discontinuation (Up to 12 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SERAPHIN, Pulmonary Arterial Hypertension, ACT-064992