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

NCT02471183 | Completed Phase 3 Results

• 1 other identifier: AC-065A304
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 15

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

Outcome Measures

Primary Outcomes (7)

• Percentage of Subjects With Sustained Treatment Transition

  A sustained treatment transition is considered if the 3 following criteria are met a) being on study treatment (selexipag) at Week 16, and b) not having a study treatment interruption(s) of a total of 8 days or more prior to Week 16, and c) absence of inhaled treprostinil or any prostanoid treatment after Week 8 up to Week 16. The percentage of subjects with a sustained treatment transition is calculated with 95% confidence interval (CI) using the Clopper-Pearson method.

  At Week 16

• Percentage of Subjects With Treatment-emergent Adverse Events (AEs),

  Percentage of subjects with treatment-emergent AEs (serious and non serious), regardless of relationship to selexipag

  26 weeks on average (from the first dose of selexipag up to 30 days after the last dose of selexipag)

• Number of Subjects With Adverse Events Leading to Premature Discontinuation of Selexipag

  Number of subjects with adverse events leading to premature discontinuation of selexipag is determined from the first dose of selexipag up to the last dose of selexipag

  Up to 22 weeks on average

• Absolute Change From Baseline Over Time in Blood Pressure

  Both systolic(SBP) and diastolic (DBP) arterial blood pressure were measured in a sitting position after at least 5 minutes of rest at scheduled time points. Median change from baseline to pre-specified post-baseline visits are calculated

  Baseline, Week 4, Week 12, Week 16

• Absolute Change From Baseline Over Time in Heart Rate (HR)

  Pulse rate is measured after at least 5 minutes of rest in a sitting position. Median change from baseline to pre-specified post-baseline visits are calculated.

  Baseline, Week 4, Week 12, Week 16

• Maximal Tolerated Dose

  This is the individual maximal tolerated dose (MTD) observed at Week 12 in the subjects still on selexipag at Week 16. MTD is defined as the dose of selexipag reached with the last dose change up to Week 12

  At Week 12, in subjects still on selexipag at Week 16

• Time to Discontinuation of Inhaled Treprostinil.

  Median time from baseline (Day1) to the end of down-titration of inhaled treprostinil is calculated

  Baseline to Week 16

Secondary Outcomes (4)

• Percentage of Subjects With WHO Functional Class (FC) Change From Baseline

  Baseline and Week 16

• Absolute Change in 6-minute Walk Distance (6MWD) at Trough

  Baseline and Week 16

• Percentage of Patients With Change in 6-minute Walk Distance (6MWD)

  Baseline and Week 16

• Geometric Mean of the Ratio in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) of Week 16 to Baseline

  Baseline and Week 16

Other Outcomes (1)

• Change From Baseline to Week 16 in the Treatment Satisfaction Questionnaire for Medication Questionnaire (TSQM II)

  Baseline and Week 16

Study Arms (1)

Selexipag, Open Label

EXPERIMENTAL

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.

Drug: Selexipag

Interventions

Selexipag 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).

Also known as: Uptravi, ACT-293987

Selexipag, Open Label

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (15)

UCSD Medical Center -La Jolla

La Jolla, California, United States

Location

UCSF Medical Center

San Francisco, California, United States

Location

Harbor UCLA Medical Center

Torrance, California, United States

Location

Emory University

Atlanta, Georgia, United States

Location

Piedmont Healthcare Research Institute

Austell, Georgia, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Duke Unversity

Durham, North Carolina, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, United States

Location

UT Southwestern

Dallas, Texas, United States

Location

Houston Methodist Hospital

Houston, Texas, United States

Location

Sentara Cardiovascular Research Instistute

Norfolk, Virginia, United States

Location

Related Publications (1)

• 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.

  PMID: 30391194 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

selexipag

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Global Post approval studies Director
• Organization: Actelion Pharmaceuticals Ltd

lperchen@its.jnj.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 15, 2015
• Study Start: October 12, 2015
• Primary Completion: December 5, 2016
• Study Completion: December 5, 2016
• Last Updated: January 23, 2018
• Results First Posted: December 28, 2017

Record last verified: 2017-12

Locations

US (15)