Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Selexipag
Intervention description: 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 MeSH terms: Selexipag
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.