Study of the drug macitentan in patients with pulmonary arterial hypertension in order to test the French, Italian, and Spanish translations of a patient questionnaire called PAH-SYMPACT.

• Register: EUCTR
• Last refreshed on: 5 March 2018
• Main ID: EUCTR2013-003462-14-IT
• Date of registration: 20/11/2013
• Prospective Registration: Yes
• Primary sponsor: ACTELION Pharmaceuticals Ltd.
• Public title: Study of the drug macitentan in patients with pulmonary arterial hypertension in order to test the French, Italian, and Spanish translations of a patient questionnaire called PAH-SYMPACT.
• Scientific title: A multi-center, open-label, single-arm, Phase 3b study of macitentan in patients with pulmonary arterial hypertension to psychometrically validate the French, Italian and Spanish versions of the PAH-SYMPACT™ - ORCHESTRA
• Date of first enrolment: 10/12/2013
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003462-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Italy, Spain

Contacts

• Name: Global Medical Information
• Affiliation: Actelion Pharmaceuticals Ltd.

• Name: Global Medical Information
• Affiliation: Actelion Pharmaceuticals Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent prior to initiation of any study-mandated procedure.
2. Patients with symptomatic PAH in WHO Functional Class (FC) II or III.
3. Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:
a. Idiopathic, or,
b. Heritable, or,
c. Drug or toxin induced, or,
d. Associated with one of the following:
i. Connective tissue disease,
ii. Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair,
iii. HIV infection.
4. Documented hemodynamic diagnosis of PAH by right heart catheterization – performed at any time prior to Screening showing:
a. Resting mean pulmonary arterial pressure (mPAP) = 25 mmHg and,
b. Resting pulmonary vascular resistance (PVR) > 240 dyn·s·cm-5 and,
c. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) = 15 mmHg.
5. 6-minute walk distance (6MWD) = 150 m at Screening.
6. Able to fluently speak and read the local language.
7. Men or women aged 18–80; women of childbearing potential must:
a. have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly serum pregnancy tests, and,
b. agree to use two reliable methods of contraception in parallel, from Screening Visit 1 until 1 month after study drug discontinuation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1. Known moderate-to-severe obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 80% of predicted, with FEV1 / forced vital capacity [FVC] < 70%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
2. Known moderate-to-severe restrictive lung disease (i.e., total lung capacity [TLC] < 60% of predicted value).
3. Hemoglobin < 100g/L at Screening.
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 X the upper limit of the normal range (ULN) at Screening.
5. Patients undergoing dialysis.
6. Systolic blood pressure (SBP) < 90 mmHg at Screening.
7. Body weight < 40 kg at Screening.
8. Known concomitant life-threatening diseases with a life expectancy of < 12 months.
9. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial.
10. Treatment with intravenous or subcutaneous prostacyclin or prostacyclin analogs within 3 months prior to Visit 2, or scheduled to receive any of these compounds during the trial.
11. Treatment with soluble guanylate cyclase stimulator (riociguat) within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial.
12. Patients who changed the dose of or discontinued phosphodiesterase type-5 inhibitors (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers within 3 months prior to Visit 2.
13. Initiation of diuretics within 1 week prior to the Baseline period.
14. Patients on oral diuretics in whom the dose has not been stable for at least 1 week prior to the Baseline period.
15. Treatment with cytochrome P450 (CYP) 3A inducers within 4 weeks prior to Visit 2.
16. Recently started (< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise.
17. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study.
18. Known hypersensitivity to macitentan or its excipients or drugs of the same class.
19. Treatment with another investigational drug within 3 months prior to Visit 2.
20. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension
MedDRA version: 16.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Current Sponsor code: ACT-064992
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: To assess the safety of macitentan in patients with PAH

Main Objective: - To evaluate the psychometric characteristics of reliability and construct validity of the French, Italian and Spanish versions of the PAH-SYMPACT™
- To evaluate the ability of the French, Italian and Spanish versions of the PAH-SYMPACT™ to detect change

Primary end point(s): The study psychometrically validates the French, Italian and Spanish versions of the PAH-SYMPACT™ in patients with PAH

Timepoint(s) of evaluation of this end point: At screening, twice during baseline, twice during treatment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Visits 1, 2, 3, 4 and 5

Secondary end point(s): Safety endpoints
- Treatment-emergent adverse events (AEs).
- AEs leading to premature discontinuation of study drug.
- Treatment-emergent serious adverse events (SAEs).
- Change from Baseline to Week 16 in vital signs, i.e., supine SBP, DBP, and HR.
- Proportion of patients with treatment-emergent ALT and/or AST abnormality (> 3, > 5, and > 8 X ULN) associated or not with total bilirubin > 2 X ULN, up to EOT.
- Proportion of patients with treatment-emergent hemoglobin abnormality (= 100 g/L, and = 80 g/L), up to EOT.

Secondary ID(s)

AC-055-310

Source(s) of Monetary Support

ACTELION Pharmaceuticals Ltd.