Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.

A Multi-center, Double-blind, Placebo-controlled Phase 4 Study in Patients With Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Daily Life Physical Activity and Patient's Self-reported Symptoms and Their Impacts

The primary objective of this study is to evaluate the effect of selexipag on the physical activity of patients with pulmonary arterial hypertension (PAH) in their daily life, by using a wearable wrist device (actigraph). The actigraph will collect data on daily life physical activity in the patient's real environment. In addition, the PAH symptoms and their impacts will be assessed by using an electronic patient reported outcome measure in the patient's real environment. Patients will be assigned randomly to either selexipag or placebo.

This study is designed as exploratory with the purpose to generate hypotheses on new endpoints

Inclusion Criteria:

• Male or female between 18 and 75 years old inclusive.

• Women of childbearing potential must have a negative serum pregnancy test at planned visits and use an acceptable method of birth control from screening up to 30 days after study treatment discontinuation.

• Symptomatic pulmonary arterial hypertension (PAH) belonging to one of the following subgroups only:

  • Idiopathic
  • Heritable
  • Drug or toxin induced
  • Associated with one of the following: connective tissue disease; HIV infection; corrected simple congenital heart disease.

• With the following hemodynamic characteristics assessed by right heart catheterization (RHC) prior to randomization:

  • Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
  • Pulmonary vascular resistance (PVR) ≥ 240 dyn•sec/cm5 (or 3 Wood Units)
  • Pulmonary artery wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤ 15 mmHg.

• Treatment with an endothelin receptor antagonist (ERA) for at least 90 days and on a stable dose for 30 days prior to randomization.

• If an ERA is given in combination with a phosphodiesterase-5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator, these treatments must be ongoing for at least 90 days and on a stable dose for 30 days prior to randomization.

• WHO functional class (FC) II or III at randomization

• 6-minute walk distance (6MWD) ≥ 100 m at screening.

• Ability to walk without a walking aid.

• Valid baseline data for daily life physical activity (DLPA) and PAH-SYMPACT®.

Exclusion Criteria:

• Patients on a PAH-specific monotherapy targeting the nitric oxide pathway (i.e. PDE-5 inhibitor or sGC stimulator).
• Patients treated with prostacyclin, prostacyclin analog or selexipag within 3 months prior to screening.
• Any hospitalization during the last 30 days prior to screening.
• Severe coronary heart disease or unstable angina.
• Documented severe hepatic impairment or severe renal insufficiency at screening.
• Participation in a cardio-pulmonary rehabilitation program based on exercise training within 8 weeks prior to screening
• Any factor or condition likely to affect full participation in the study or compliance with the protocol (such as adherence to protocol mandated procedures), as judged by the investigator.