None listed
Conditions
Interventions
Drug : Among enrolled patients with pulmonary arterial hypertension, subjects with a history of administration of Opsumit tablets will be allocated to Part B, while the others will be randomly assigne
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [Part A] - Among patients with pulmonary arterial hypertension (WHO Group I) who are classified as WHO (World Health Organization) Functional Class II to III, any of the following diseases has been diagnosed. (1) idiopathic pulmonary hypertension (2) hereditary pulmonary hypertension (3) pulmonary arterial hypertension associated with connective tissue disease (4) Pulmonary arterial hypertension with fully surgically corrected congenital heart disease at least a year ago - Patients who have not been treated with endothelin receptor antagonists (ERAs) for pulmonary arterial hypertension within 3 months of screening and have not achieved treatment goals. (Treatment goal: Improvement to WHO functional class I~II stage and maintenance in pulmonary arterial hypertension.) - Patients with a 6-minute walking distance (6MWD) measured at the time of diagnosis or screening for pulmonary arterial hypertension of 150m or more, but less than 480m. [Part B] - Among patients with pulmonary arterial hypertension (WHO Group I) who are classified as WHO (World Health Organization) Functional Class II to III, any of the following diseases has been diagnosed. (1) idiopathic pulmonary hypertension (2) hereditary pulmonary hypertension (3) pulmonary arterial hypertension associated with connective tissue disease (4) Pulmonary arterial hypertension associated with congenital heart disease: with or without surgical complete correction of congenital heart disease, including Eisenmenger syndrome - Patients who have been administered Opsumit (Macitentan) at a stable dose for 12 weeks or more for the treatment of pulmonary arterial hypertension. [Part A and Part B] - Patients who are male or female and are aged 18 years or older but no more than 79 years at the time of signing the informed consent form. - Patients with all of the following hemodynamic diagnoses as measured by right cardiography at the time of diagnosis of pulmonary artery hypertension (1) Mean pulmonary artery pressure = 25mmHg (2) Pulmonary capillary wedge pressure = 15mmHg, or if pulmonary capillary wedge pressure measurement is not possible, left ventricular end-diastolic pressure = 15mmHg. (3) Pulmonary vascular resistance exceeds 3WU(Wood Unit)(=240 dyne-sec/cm5). * For both Part A and Part B, if there is at least one previous right heart catheterization result, it can be used. - For women of childbearing potential, patients with negative pregnancy test results at screening and baseline. (Women of childbearing potential should be able to avoid pregnancy during the clinical trial period by using appropriate contraception, and no plans for pregnancy should be confirmed for up to 1 month after discontinuation/termination of the clinical trial.) - Patients who voluntarily decided to participate in this clinical trial after receiving an explanation about the clinical trial and fully understanding and agreeing to follow all instructions voluntarily in writing.
Exclusion criteria
Exclusion criteria: - People weighing less than 40 kg - People with a body mass index (BMI) exceeding 35 kg/m2 - People with systolic blood pressure below 90 mmHg (However, patients who maintain systolic blood pressure below 70 mmHg without symptoms may be eligible for study participation at the discretion of the investigator) - Patients with left ventricular ejection fraction (LV EF) less than 40% as assessed by echocardiography - Patients who have been hospitalized due to worsening pulmonary arterial hypertension within 3 months prior to screening - Patients who currently have or have had any of the following conditions: (1) Stroke that causes motor dysfunction or Acute stroke within 6 months. (2) End-stage renal disease (eGFR (glomerular filtration rate) < 15 mL/min/1.73m2) eGFRcr = 142 x min(Serum creatinine/?, 1)a x max(Serum creatinine/?, 1)-1.200 x 0.9938Age(if female×1.012) * Note: Adjustment factor is not required for males ? = 0.7 (female) or 0.9 (male) a = -0.241 (female) or -0.302 (male) (3) End-stage kidney disease requiring dialysis (4) Valvular disease Grade 3 or higher (excluding tricuspid valve) (5) Acute pulmonary embolism or deep vein thrombosis (6) Moderate to severe chronic obstructive pulmonary disease (COPD) (7) Moderate to severe restrictive lung disease (8) Child class C or Acute hepatitis requiring treatment (regardless of the presence of cirrhosis) - Patients with a history of therapeutic procedures related to coronary artery disease or have not exceeded three months since experiencing a myocardial infarction - Patients who clinically show significant liver disease, with total bilirubin levels exceeding three times the upper limit of normal, and concurrently have AST or ALT levels exceeding three times the upper limit of normal - Patients who have any of the following treatment histories: (1) Patients who received potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir) within 4 weeks prior to screening (2) Patients who received potent CYP3A4 inducers (e.g., rifampicin, St. John's wort, carbamazepine, phenytoin) within 4 weeks prior to screening (3) Patients currently participating in another clinical trial - Pregnant or lactating women - Women and men of childbearing potential who do not agree to use reliable contraception* until 30 days after the end of the clinical trial period or discontinuation/termination of the clinical trial *Hormonal contraceptives, intrauterine devices, barrier methods (for men or women) in combination with spermicides, and surgical sterilization procedures (tubal ligation, vasectomy, and hysterectomy) - People with hypersensitivity to the active ingredient (macitentan) or any of the components of the investigational product for this clinical trial - Patients with genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption - Patients with hypersensitivity or allergy history to soybeans or peanuts - Patients with current or past history of alcohol and/or substance abuse - Patients who started or plan to start a cardiac rehabilitation program within 8 weeks prior to screening or during the clinical trial period - Other patients deemed unsuitable for this clinical trial at the discretion of the investigator (patients who may not follow the clinical trial procedures, etc.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A : Change in six-minute walk distance (6MWD) at 12 weeks compared to baseline;Part B : Adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A : Change in echocardiography at 12 weeks compared to baseline;Part A : Change in NT-proBNP(N-terminal pro-brain natriuretic peptide) at 12 weeks compared to baseline;Part A : Proportion of subjects without clinical deterioration at 12 weeks compared to baseline;Part A : Change in WHO Functional class at 12 weeks compared to baseline;Part A : Proportion of subjects and using days of Pulmonary Arterial Hypertension drugs other than investigational product during this clinical study period;Part A : Adverse Events;Part A : Laboratory tests(Hematology/Biochemistry/Urinalysis), Physical examination, Vital signs, Weight;Part B : Laboratory tests(Hematology/Biochemistry/Urinalysis), Physical examination, Vital signs, Weight;Part B : Change in six-minute walk distance (6MWD) at 24 weeks compared to baseline;Part B : Change in NT-proBNP(N-terminal pro-brain natriuretic peptide) at 24 weeks compared to baseline;Part B : Proportion of subjects without clinical deterioration at 24 weeks compared to baseline;Part B : Change in WHO Functional class at 12 weeks compared to baseline;Part B : Proportion of subjects and using days of Pulmonary Arterial Hypertension drugs other than investigational product during this clinical study period | — |
Countries
Korea, Republic of
Contacts
Public ContactSooYeon Lee
Samsung Medical Center
Outcome results
None listed