E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension |
|
E.1.1.1 | Medical condition in easily understood language |
Pulmonary Arterial Hypertension is an increase in blood pressure in the
pulmonary arteries leading to shortness of breath, dizziness, fainting
and other symptoms. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of selexipag on daily life physical activity (DLPA)
of patients with pulmonary arterial hypertension (PAH) as assessed by a
wearable actigraphy device. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of selexipag on PAH symptoms and their impacts in patients’ daily life.
• To evaluate the effect of selexipag on exercise capacity, and disease severity in patients with PAH.
• To evaluate the safety and tolerability of selexipag in patients with PAH. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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.
- Possible treatment with a Phosphodiesterase-5 inhibitor or sGC
stimulator 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®. |
|
E.4 | Principal 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 at any time prior to Day 1.
- Any hospitalization during the last 30 days prior to screening (Visit 1).
- Severe coronary heart disease or unstable angina.
- Documented severe hepatic impairment or severe renal insufficiency at screening (Visit 1).
- 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline to Week 24 / EOT in actigraphy-assessed daily life physical activity (DLPA) as measured by:
. Daily time spent (minutes) in non-sedentary activity
(> 100 activity counts per minute)
. Percentage of daily time spent in non-sedentary activity (> 100 activity counts per minute)
. Total DLPA in counts/min
. Sleep variables: Total sleep time (minutes); wake after sleep onset (minutes); number of awakenings, sleep efficiency (percentage) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change from baseline to Week 24 / EOT for following PAH SYMPACT® domain scores:
. Cardiovascular symptom domain score
. Cardiopulmonary symptom domain score
. Physical impact domain score
. Cognitive/emotional impact domain score
- Change from baseline to Week 24 / EOT for following variables:
. WHO FC
. 6MWD
. Borg dyspnea index at 6MWT
. N-terminal pro b-type natriuretic peptide (NT-proBNP) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
effect of selexipag on daily life physical activity of patients with pulmonary arterial hypertension |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
France |
Germany |
Ireland |
Netherlands |
Norway |
Portugal |
Sweden |
Switzerland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
end of study telephone call 30 days after end of treatment of the last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |