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

Actelion Pharmaceuticals

Status and phase: Completed; Phase 4

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Placebo; Drug: Selexipag

Study type: Interventional

Funder types: Industry

Identifiers

NCT03078907

AC-065A404

Details and patient eligibility

About

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.

Full description

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

Enrollment: 108 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 2 patient groups, including a placebo group

Selexipag

Experimental group

Description:

Selexipag is up-titrated from Day 1 to Week 12 to the individualized highest tolerated dose (HTD), which can range from 200 mcg b.i.d. to 1600 mcg b.i.d., in 200 mcg steps starting with 200 mcg b.i.d. Then, the dose is increased in increments of 200 mcg b.i.d., usually at weekly intervals, depending on the dose tolerability. Up-titration is followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Treatment:

Drug: Selexipag

Placebo

Placebo Comparator group

Description:

Regimen and titration scheme similar to those in the selexipag group

Treatment:

Drug: Placebo