Clinical trial NCT02471183: Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension
Official title: Multicenter, Open-label, Single-group Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Adult Patients With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2015-06-15
Enrollment: 34
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: 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.


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.

Primary outcomes:
measure: Percentage of Subjects With Sustained Treatment Transition
timeFrame: At Week 16
measure: Percentage of Subjects With Treatment-emergent Adverse Events (AEs),
timeFrame: 26 weeks on average (from the first dose of selexipag up to 30 days after the last dose of selexipag)
measure: Number of Subjects With Adverse Events Leading to Premature Discontinuation of Selexipag
timeFrame: Up to 22 weeks on average
measure: Absolute Change From Baseline Over Time in Blood Pressure
timeFrame: Baseline, Week 4, Week 12, Week 16
measure: Absolute Change From Baseline Over Time in Heart Rate (HR)
timeFrame: Baseline, Week 4, Week 12, Week 16
measure: Maximal Tolerated Dose
timeFrame: At Week 12, in subjects still on selexipag at Week 16
measure: Time to Discontinuation of Inhaled Treprostinil.
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Percentage of Subjects With WHO Functional Class (FC) Change From Baseline
timeFrame: Baseline and Week 16
measure: Absolute Change in 6-minute Walk Distance (6MWD) at Trough
timeFrame: Baseline and Week 16
measure: Percentage of Patients With Change in 6-minute Walk Distance (6MWD)
timeFrame: Baseline and Week 16
measure: Geometric Mean of the Ratio in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) of Week 16 to Baseline
timeFrame: Baseline and Week 16
Other outcomes:
measure: Change From Baseline to Week 16 in the Treatment Satisfaction Questionnaire for Medication Questionnaire (TSQM II)
timeFrame: Baseline and Week 16
Locations:
city: La Jolla
country: United States
facility: UCSD Medical Center -La Jolla
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Austell
country: United States
facility: Piedmont Healthcare Research Institute
state: Georgia
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke Unversity
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Instistute
state: Virginia
Study officials:
References:
citation: 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.