Safety Study of the Switch From Oral Selexipag to Intravenous Selexipag in Subjects With Stable Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The development of selexipag for intravenous administration will be useful to avoid treatment interruptions in patients with pulmonary arterial hypertension (PAH) already treated with selexipag administered orally as tablets (Uptravi®). The target population for intravenous selexipag includes those PAH patients who are hospitalized and are unable to swallow tablets of Uptravi. The primary objective of this study is to assess whether it is safe for patients with PAH to temporarily change from selexipag tablets (Uptravi®) to selexipag given directly into a vein (intravenous selexipag), and then switching back to the initial oral dose of selexipag.

Detailed Description
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After screening (Visit 1), each subject will participate in the following consecutive treatment periods: Period 1(treatment with oral selexipag at Visit 2/Day 1), Period 2 (treatment with intravenous selexipag at Visit 2/ Day 2 and Day 3), Period 3 (treatment with oral selexipag starting in the evening of Visit 2/Day 3 and ending 7 to 11 days later at Visit 3). Then a safety follow-up period is planned up to end of study visit (EOS), which occurs between Day 33 and Day 40.

Official Title
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A Multicenter, Open-label, Single-sequence Cross-over Study to Assess Safety, Tolerability, and Pharmacokinetics of Intravenous Selexipag in Subjects With Stable Pulmonary Arterial Hypertension Switching From an Oral Stable Dose of Selexipag

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: i.v. selexipag
* Drug: oral selexipag (Uptravi)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form prior to any study-mandated procedure. Male and female subjects aged from 18 to 75 years (inclusive), Subjects with stable pulmonary arterial hypertension (PAH) defined as WHO Functional Class I-III at Visit 1 and Visit 2, and no change (i.e., introduction or dose change) in PAH-specific medication (i.e., ERA, PDE-5 inhibitor or sGC stimulator) and diuretics in the last 28 days prior to Visit 2. Subjects currently treated with Uptravi® at a stable dose (i.e. unchanged dose) for at least 28 days before Visit 2. Women of childbearing potential must have a negative pregnancy test at Visit 1 (screening) and Visit 2. Exclusion Criteria: Pregnant, planning to become pregnant or lactating. Known and documented moderate or severe hepatic impairment. Subjects having received gemfibrozil at any time since initiation of Uptravi®. Treatment with any prostacyclin and prostacyclin analogs within 28 days prior to Visit 1. SBP < 90 mmHg at Visit 1 or at Visit 2. Known or suspected uncontrolled hyperthyroidism. Severe renal failure and ongoing or planned dialysis. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results. Known concomitant life-threatening disease with a life expectancy < 12 months. Treatment with another investigational treatment within 3 months of Visit 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Selexipag<br>Subjects with stable pulmonary arterial hypertension (PAH) and currently treated with a stable oral dose of Uptravi will be switched to i.v. selexipag from Day 2 to Day 3 (2 infusions on Day 2 and 1 infusion on Day 3). Otherwise, they will continue with their current oral selexipag treatment throughout the study. | Drug: i.v. selexipag<br>* Selexipag for intravenous administration, twice daily as an infusion over 87 min. The dose is individualized for each subject to correspond to his/her current oral dose of Uptravi®.<br>* Other names: ACT-293987;Drug: oral selexipag (Uptravi)<br>* Uptravi is used as an auxiliary medicinal product, as part of the PAH standard treatment and administered according to the local prescribing information<br>* Other names: ACT-293987;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Adverse Event (AE) | AE is any untoward medical event that occurs in a participant during the course of the study whether or not considered by the investigator as related to the study treatment. | From Day 1 to Day 37 | 
| Number of Participants With Prostacyclin-associated Adverse Events | Prostacyclin-associated AE include headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia. | From Day 1 to Day 37 | 
| Number of Participants With Adverse Event Related to Injection Site Reactions | This is the number of participants with at least one clinically significant reaction at the injection site (e.g., erythema/redness, tenderness, swelling, induration, hemorrhage at the injection site) occurring on the days of intravenous (iv) selexipag injection. | From Day 2 to Day 3 | 
| Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation | This is the number of subjects who discontinued the i.v. selexipag treatment due to prostacyclin-associated adverse events (headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia). | From Day 2 to Day 3 | 
| Number of Participants With PAH-related Adverse Events | This is the number of participants with at least one AE considered to be related to pulmonary arterial hypertension during the course of the study. | From Day 1 to Day 37 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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switch, intravenous, selexipag