Clinical trial NCT03187678: Safety Study of the Switch From Oral Selexipag to Intravenous Selexipag in Subjects With Stable Pulmonary Arterial Hypertension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: switch
intravenous
selexipag
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-06-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With at Least One Adverse Event (AE)
timeFrame: From Day 1 to Day 37
measure: Number of Participants With Prostacyclin-associated Adverse Events
timeFrame: From Day 1 to Day 37
measure: Number of Participants With Adverse Event Related to Injection Site Reactions
timeFrame: From Day 2 to Day 3
measure: Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation
timeFrame: From Day 2 to Day 3
measure: Number of Participants With PAH-related Adverse Events
timeFrame: From Day 1 to Day 37
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical center - PULM VASCULAR DIV
state: California
city: Boston
country: United States
facility: TUFTS New England Medical Center - PULM / CRITICAL CARE & SLEEP
state: Massachusetts
city: Cleveland
country: United States
facility: Cleveland Clin Foundation - Dept of Pulm & Critical Care Med
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen und Marburg GmbH, Medizinische Klinik und Poliklinik II, Pneumologie
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Pneumologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie
Study officials:
affiliation: Actelion
name: Ralph Preiss
role: STUDY_DIRECTOR
References:
citation: 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.