Long-term Safety Evaluation of Tadalafil and Macitentan in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

The primary objective of this study is to evaluate the long-term **safety** of the respective study interventions in participants treated for **pulmonary arterial hypertension** and **chronic thromboembolic pulmonary hypertension**. This is clinically relevant as it aims to ensure the sustained safety profile of the interventions, which include the active substances **tadalafil** and **macitentan**, administered in the form of film-coated tablets. The study is designed as a prospective, open-label, platform study for long-term follow-up of participants who have previously been involved in parent studies related to these conditions.

The clinical trial involves a total of **59 participants** diagnosed with **pulmonary arterial hypertension** or **chronic thromboembolic pulmonary hypertension**. The study population includes both male and female subjects, encompassing a broad age range that includes pediatric participants as young as 2 years old. Participants were selected based on their previous involvement in a sponsor parent study, where they were treated with oral macitentan, selexipag, or a fixed-dose combination of macitentan and tadalafil. The trial population includes individuals who may continue to benefit from the study interventions, with no alternative means of access to equivalent approved therapies identified. The study also considers vulnerable populations, ensuring informed consent is obtained from participants or their legally acceptable representatives. Lifestyle factors such as diet and physical activity are not specified, but female participants of childbearing potential are required to adhere to specific contraceptive guidelines throughout the study duration. The trial aims to evaluate the long-term safety of the study interventions in the treated participants.

The clinical trial is designed to evaluate the long-term safety of study interventions in participants with **pulmonary arterial hypertension** and **chronic thromboembolic pulmonary hypertension**. This is a prospective, open-label, platform study that will follow participants who have completed a parent study involving the use of oral **macitentan**, **tadalafil**, or a fixed-dose combination of these agents. The trial is expected to run until December 2027, with participant recruitment having commenced in May 2022. The study will involve multiple visits, starting with an inclusion visit where eligibility is confirmed, followed by regular follow-up visits to monitor safety and efficacy, and concluding with an end-of-study visit.

Participants will be required to sign an informed consent form, and those of childbearing potential must adhere to specific contraceptive guidelines and undergo regular pregnancy testing. The trial will monitor the frequency of treatment-emergent adverse events, serious adverse events, and any discontinuations or deaths from baseline until the end of the study. The expected duration of participant involvement is up to 48 months, with conditions for early termination including the occurrence of significant adverse events or the availability of alternative approved therapies. The study interventions will be administered orally in the form of film-coated tablets, with a maximum daily dose of 50 mg for the fixed-dose combination and 10 mg for macitentan alone.

The clinical trial involves the administration of the experimental medication **JNJ-68150420**, which is a **film-coated tablet** containing the active substances **tadalafil** and **macitentan**. This medication is manufactured by Actelion Pharmaceuticals Ltd. The pharmaceutical form is a film-coated tablet, and it is administered orally. The maximum daily dose is 50 mg, with a total maximum dose of 50 mg per day. The treatment period extends up to 48 weeks. Participants are required to adhere to the dosing schedule, and compliance will be monitored throughout the study.

In addition to the experimental medication, the study also includes the administration of **Opsumit 10 mg film-coated tablets**, which contain the active substance **macitentan**. This medication is produced by Janssen-Cilag International NV. The pharmaceutical form is a film-coated tablet, and it is also administered orally. The maximum daily dose for Opsumit is 10 mg, with a total maximum dose of 10 mg per day. The treatment period for this medication is also up to 48 weeks. Participant compliance with the dosing schedule will be closely monitored to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed primarily through the evaluation of the frequency of treatment-emergent adverse events (AEs), treatment-emergent AEs leading to discontinuation, serious adverse events (SAEs), and/or deaths from baseline until the end of the study. These parameters will serve as the primary endpoints to determine the efficacy of the study interventions in participants with **Pulmonary Hypertension**. The trial is designed as a prospective, open-label, platform study for long-term follow-up of participants who have been using the study intervention in parent studies. The study will involve the administration of macitentan, tadalafil, or a fixed-dose combination of macitentan and tadalafil, with the maximum treatment period set at 48 weeks. The efficacy assessments will be conducted throughout the study duration, with data collection and analysis scheduled from the baseline until the end of the study. The trial aims to provide comprehensive data on the long-term safety and efficacy of the interventions in the specified patient population.