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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: i.v. selexipag; Drug: oral selexipag (Uptravi)

Detailed Description

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
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Giessen, Germany, 35392
    • Universitätsklinikum Giessen und Marburg GmbH, Medizinische Klinik und Poliklinik II, Pneumologie
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Pneumologie
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego Medical center - PULM VASCULAR DIV
  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1552
      • TUFTS New England Medical Center - PULM / CRITICAL CARE & SLEEP
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clin Foundation - Dept of Pulm & Critical Care Med
  • Texas
    • Dallas, Texas, United States, 75390-8550
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Selexipag; 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; 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®.; Other Names: ACT-293987; Drug: oral selexipag (Uptravi); Uptravi is used as an auxiliary medicinal product, as part of the PAH standard treatment and administered according to the local prescribing information; Other Names: ACT-293987

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Ralph Preiss, Actelion

Publications and helpful links

General Publications

• Klose H, Chin KM, Ewert R, Gall H, Parambil J, Poch D, Seyfarth HJ, Axelsen LN, Hsu Schmitz SF, Stein C, Preston IR. Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study. Respir Res. 2021 Feb 3;22(1):34. doi: 10.1186/s12931-020-01594-8.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Actual): May 29, 2018
• Study Completion (Actual): May 29, 2018

Study Registration Dates

• First Submitted: June 9, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 20, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: intravenous; selexipag; switch
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Selexipag
• Other Study ID Numbers: AC-065A309; 2016-004035-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No