Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension

NCT ID: NCT02471183

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-12
• Study Completion Date: 2016-12-05

Brief Summary

This study enrolls patients with pulmonary arterial hypertension (PAH) treated with inhaled treprostinil. During the study, the treatment with inhaled treprostinil will be tapered off and simultaneously replaced with an oral treatment (selexipag) targeting the disease in a similar way. The purpose of the study is i) to investigate the safety and tolerability of oral selexipag in patients who transition from inhaled treprostinil, ii) to investigate the effects of oral selexipag on PAH severity and exercise ability before and after transition, and iii) to gain new information about the patients experience taking oral selexipag compared to inhaled treprostinil. Study participants may stay in the study until the FDA has granted marketing authorization.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selexipag, Open Label

Subjects on inhaled treprostinil treatment participate in a 16-week main treatment period including down-titration of treprostinil to end of Week 8 and parallel up-titration of selexipag to the maximum tolerated dose (MTD) up to Week 12, for each individual patient but not above 1600 mcg twice daily.

From Week 12 up to Week 16, patients continue selexipag at their individual MTD. Patients could continue the study drug selexipag during the extended treatment period from Week 16 until commercial availability of selexipag.

Group Type: EXPERIMENTAL

Selexipag

Intervention Type: DRUG

Tablets for oral administration containing 200 micrograms (mcg) of selexipag to be administered twice a day. The individual dose is to be established during the first 12 weeks of the study. Doses are in the range from 200 micrograms (1 tablet) to 1,600 micrograms (8 tablets).

Interventions

Selexipag

Tablets for oral administration containing 200 micrograms (mcg) of selexipag to be administered twice a day. The individual dose is to be established during the first 12 weeks of the study. Doses are in the range from 200 micrograms (1 tablet) to 1,600 micrograms (8 tablets).

Intervention Type: DRUG

Other Intervention Names

Uptravi; ACT-293987

Eligibility Criteria

Inclusion Criteria

• Male and female patients aged from 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH).
• Etiology of PAH belonging to one of the following subgroups: idiopathic PAH, Heritable PAH, drug or toxin induced, associated with connective tissue disease, associated with HIV infection, associated with congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair.
• Women of childbearing potential are eligible only if the following apply: Negative serum pregnancy test at Visit 1 and a negative urine pregnancy test at Visit on Day 1, agreement to undertake monthly urine pregnancy tests during the study and up to 30 days after study drug discontinuation, agreement to use efficient methods of birth control from Visit 1 up to at least 30 days after study treatment discontinuation.
• Documented hemodynamic diagnosis of PAH by right heart catheterization (RHC).
• Inhaled treprostinil treatment ongoing for at least 90 days and at stable dose for at least 30 days prior to Day 1.
• WHO functional class (FC) II or III at Visit 1 and Visit 2.
• 6-minute walk distance (6MWD) ≥ 300 m at Visit 1.
• On background oral PAH therapy for at least 90 days and on a stable dose for 30 days prior to Visit 2. Acceptable concomitant PAH therapies are one or two of the following: a) Endothelin receptor antagonist (ERA), b) Phosphodiesterase type 5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator.

Exclusion Criteria

• Treatment with any prostacyclin or prostacyclin analogs other than inhaled treprostinil within 90 days before Day 1, or patients scheduled to receive any of these treatments within the duration of the study.
• Any hospitalization within 90 days before Day 1.
• Worsening in WHO FC within 30 days prior to Day 1.
• At any time prior to Day 1, documented moderate or severe obstructive or restrictive lung disease.
• Known or suspicion of pulmonary veno-occlusive disease (PVOD).
• Anemia: < 80 g/L (5.0 mmol/L) hemoglobin.
• Clinically relevant thyroid disease (hypo- or hyperthyroidism).
• Known and documented severe hepatic impairment.
• Uncontrolled hypertension.
• Sitting systolic blood pressure < 85 mmHg.
• Acute myocardial infarction within the last 90 days prior to Visit 1.
• History of left-sided heart disease.
• Left ventricular disease/dysfunction risk factors.
• Documented pericardial effusion within 90 days prior to Visit 1.
• Documented severe renal insufficiency.
• Receiving or having received any investigational drugs within 90 days before Day 1.
• Having received selexipag at any time before Day 1.
• Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements.
• Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training during the study.
• Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
• Known concomitant life-threatening disease with a life expectancy < 12 months.
• Females who are lactating or pregnant or plan to become pregnant during the study.
• Known hypersensitivity to any of the excipients of the drug formulation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCSD Medical Center -La Jolla

La Jolla, California, United States

UCSF Medical Center

San Francisco, California, United States

Harbor UCLA Medical Center

Torrance, California, United States

Emory University

Atlanta, Georgia, United States

Piedmont Healthcare Research Institute

Austell, Georgia, United States

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Duke Unversity

Durham, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, United States

UT Southwestern

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Sentara Cardiovascular Research Instistute

Norfolk, Virginia, United States

Countries

United States

References

Frost A, Janmohamed M, Fritz JS, McConnell JW, Poch D, Fortin TA, Miller CE, Chin KM, Fisher M, Eggert M, McEvoy C, Benza RL, Farber HW, Kim NH, Pfister T, Shiraga Y, McLaughlin V. Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study. J Heart Lung Transplant. 2019 Jan;38(1):43-50. doi: 10.1016/j.healun.2018.09.003. Epub 2018 Sep 12.

Reference Type: DERIVED

PMID: 30391194 (View on PubMed)

Other Identifiers

AC-065A304

Identifier Type: -

Identifier Source: org_study_id