A Clinical Study to Investigate the Long-term Safety of the Drug Macitentan in Patients With Pulmonary Hypertension Who Were Previously Treated With Macitentan in Clinical Studies.

Study Overview
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Brief Summary
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The aim of the trial is to study the long-term safety of macitentan and to provide continued treatment with macitentan to patients with pulmonary arterial hypertension (PAH) and Chronic thromboembolic pulmonary hypertension (CTEPH) who were previously treated with macitentan in clinical studies.

Detailed Description
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The purpose of this study is to provide continued treatment with macitentan to subjects with PAH or CTEPH who participated in parent studies and to continue to accrue long-term safety data. The design of this study is widely used in clinical programs to give participants in a clinical study access to an effective study treatment beyond completion of the parent study. This is considered the best option to collect long-term safety and tolerability information of macitentan 10 mg and survival status of participants with PAH and CTEPH. Parent study/studies refer to a number of clinical studies with macitentan that are conducted in different clinical classification of PAH and CTEPH (NCT00667823, NCT02112487, NCT02310672, NCT02968901, NCT02558231, NCT02382016, NCT02060721) and may be completed before the participants have access to commercial macitentan in their country of residence. The parent studies are fully or partially running in countries where no access to commercial macitentan is expected in the near future.

Official Title
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mUlticenter, Single-arM, Open-laBel, Long-teRm Safety Study With macitEntan in Patients With puLmonary Arterial Hypertension previousLy Treated With mAcitentan in Clinical Studies

Conditions
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Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary 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 to take part in the study before any study mandated procedure. Participants from one of the parent studies and: a) the sponsor has decided to terminate the parent study in that country and b) the participant has completed the end of treatment (EOT) Visit of the parent study Women of childbearing potential are able to take part in the study if the following applies: a) Urine pregnancy test is negative at Enrollment; b) Agreement to perform monthly urine or serum pregnancy tests during the study and up to at least 30 days after the study treatment discontinuation; and c) Agreement to adhere to the planned contraception scheme from Enrollment up to at least 30 days after study treatment discontinuation Exclusion Criteria: Hemoglobin less than 80 gram per liter (g/L) Serum Aspartate aminotransferase (AST) and/or alanine aminotransferases (ALT) more than three times the upper limit of normal range Known and documented history of severe hepatic impairment that is Child-Pugh Class C. Pregnant, planning to become pregnant, or breastfeeding Known hypersensitivity to macitentan, its excipients, or drugs of the same class Planned or current treatment with another investigational treatment up to 3 months prior to Enrollment Any known factor or disease that may interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)
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
Interventional Model Description: The study is designed as an open-label, single-arm, multicenter trial in which all participants roll over from a parent study in order to continue their dose of macitentan 10 mg once every day as already received in the parent study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label macitentan 10 mg<br>10 mg macitentan film coated tablet, administered orally once daily | Drug: macitentan<br>* macitentan 10 mg, film-coated tablet, oral use<br>* Other names: JNJ-67896062;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident Rate of Treatment-emergent Adverse Event | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A treatment-emergent AE is any AE temporally associated with the use of study treatment. | From Day 1 to End of study (EoS) visit (an average of 3 years) | 
| Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatment | Any AE will be recorded that 1) is (temporally) associated with the use of study treatment whether or not considered by the investigator as related to study treatment and 2) leads to premature discontinuation of study medication. | From Day 1 to EoS visit (an average of 3 years) | 
| Incident rate of treatment-emergent serious adverse events (SAEs) | Any SAE as defined by the ICH guidelines will be recorded. Any hepatic AE that leads to discontinuation of study treatment will be defined as SAE. | From Day 1 to EoS visit (an average of 3 years) | 
| Number of pregnancies with maternal exposure to macitentan | Pregnancies with maternal exposure to macitentan will be recorded. | From Day 1 to EoS visit (an average of 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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macitentan, long-term safety, open-label, single-arm