The endothelin receptor antagonist macitentan showed significant improvement compared with placebo in pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD) in inoperable CTEPH patients in the phase II MERIT-1 trial (AC-055E201, NCT02021292). However, in the MERIT-1 trial Japanese patients were not included. Therefore, in line with Japan's medical environment, this phase III study is to confirm the efficacy and safety of macitentan in Japanese CTEPH patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
macitentan 10 mg, film-coated tablet, oral use
Fukuoka University Nishijin Hospital
Fukuoka, Japan
Fukushima Medical University Hospital
Fukushima, Japan
Kagoshima University Hospital
Kagoshima, Japan
Nara Medical University Hospital
Kashihara, Japan
Kokura Kinen Hospital
Kitakyushu, Japan
Kobe University Hospital
Kobe, Japan
Saitama Cardiovascular and Respiratory Center
Kumagaya, Japan
Kure Kyosai Hospital
Kure, Japan
Kurume University Hospital
Kurume, Japan
Toho University Ohashi Medical Center
Meguro-ku, Japan
...and 13 more locations
Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16
The resistance in the artery carrying blood to the lungs is called PVR. The PVR is the resistance in the artery carrying blood to the lungs and that has to be overcome by the right ventricle in heart in order to let blood flow to the lungs occur. The ratio in PVR at rest indicates the efficacy of macitentan in patients with CTEPH. The ratio in PVR at rest is calculated as PVR at Week 16 divided by baseline PVR. The ratio in PVR at rest from baseline to Week 16 of administration of macitentan is evaluated in subjects with CTEPH who are not indicated for pulmonary endarterectomy (PEA) and/or subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after PEA and/or balloon pulmonary angioplasty (BPA).
Time frame: From Baseline to Week 16
Change from baseline to Week 16 in PVR at rest
The PVR at rest will be calculated to evaluate the change in PVR at rest from pre-dosing (baseline) to post-dosing (Week 16).
Time frame: From baseline to Week 16
Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest
The indexed PVR (PVRI) at rest will be calculated to evaluate the change in PVRI at rest from pre-dosing (baseline) to post-dosing (Week 16).
Time frame: From baseline to Week 16
Change from baseline to Week 24 in 6-minute walk distance (6MWD)
The purpose of the 6-minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint evaluates the change in 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Time frame: From baseline to Week 24
Change from baseline to Week 24 in Borg dyspnea index
The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement. This endpoint evaluates the change in the Borg dyspnea index assessed at the end of measuring the 6MWD from pre-dosing (baseline) to post-dosing (Week 24).
Time frame: From baseline to Week 24
Change from baseline to Week 24 in WHO functional class (WHO FC)
This endpoint evaluates the change of WHO functional class from pre-dosing (baseline) to post-dosing (Week 24). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.
Time frame: From baseline to Week 24
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