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

Actelion20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pulmonary Arterial Hypertension

Interventions

i.v. selexipagDRUG

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®.

oral selexipag (Uptravi)DRUG

Uptravi is used as an auxiliary medicinal product, as part of the PAH standard treatment and administered according to the local prescribing information

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (8)

University of California San Diego Medical center - PULM VASCULAR DIV

La Jolla, California, United States

TUFTS New England Medical Center - PULM / CRITICAL CARE & SLEEP

Boston, Massachusetts, United States

Cleveland Clin Foundation - Dept of Pulm & Critical Care Med

Cleveland, Ohio, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Universitätsklinikum Giessen und Marburg GmbH, Medizinische Klinik und Poliklinik II, Pneumologie

Giessen, Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B

Greifswald, Germany

Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Pneumologie

Hamburg, Germany

Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie

Leipzig, Germany

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: From Day 1 to Day 37