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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03187678
• Other study ID #: AC-065A309
• Secondary ID: 2016-004035-21
• Status: Completed
• Phase: Phase 3
• Start date: December 4, 2017
• Est. completion date: May 29, 2018

Study information

• Verified date: May 2019
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 29, 2018
• Est. primary completion date: May 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

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®.
• 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

Locations

Country	Name	City	State
Germany	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
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	University of California San Diego Medical center - PULM VASCULAR DIV	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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