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

Primary Purpose

Pulmonary Arterial Hypertension

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

i.v. selexipag

oral selexipag (Uptravi)

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring switch, intravenous, selexipag

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of California San Diego Medical center - PULM VASCULAR DIV
TUFTS New England Medical Center - PULM / CRITICAL CARE & SLEEP
Cleveland Clin Foundation - Dept of Pulm & Critical Care Med
University of Texas Southwestern Medical Center
Universitätsklinikum Giessen und Marburg GmbH, Medizinische Klinik und Poliklinik II, Pneumologie
Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B
Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Pneumologie
Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selexipag

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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).

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03187678

First Posted

June 9, 2017

Last Updated

May 20, 2019

Sponsor

Actelion

1. Study Identification

Unique Protocol Identification Number

NCT03187678

Brief Title

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

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

December 4, 2017 (Actual)

Primary Completion Date

May 29, 2018 (Actual)

Study Completion Date

May 29, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Actelion

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension

Keywords

switch, intravenous, selexipag

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Selexipag

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

i.v. selexipag

Other Intervention Name(s)

ACT-293987

Intervention Description

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®.

Intervention Type

Drug

Intervention Name(s)

oral selexipag (Uptravi)

Other Intervention Name(s)

ACT-293987

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With at Least One Adverse Event (AE)

Description

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

Title

Number of Participants With Prostacyclin-associated Adverse Events

Description

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

Title

Number of Participants With Adverse Event Related to Injection Site Reactions

Description

Time Frame

From Day 2 to Day 3

Title

Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation

Description

Time Frame

From Day 2 to Day 3

Title

Number of Participants With PAH-related Adverse Events

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ralph Preiss

Organizational Affiliation

Actelion

Official's Role

Study Director

Facility Information:

Facility Name

University of California San Diego Medical center - PULM VASCULAR DIV

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

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

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111-1552

Country

United States

Facility Name

Cleveland Clin Foundation - Dept of Pulm & Critical Care Med

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-8550

Country

United States

Facility Name

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

City

Giessen

ZIP/Postal Code

35392

Country

Germany

Facility Name

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B

City

Greifswald

ZIP/Postal Code

17475

Country

Germany

Facility Name

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

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

33536021

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.

Results Reference

derived

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

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