pulmonary arterial hypertension
Conditions
Interventions
investigational material(s)
Generic name etc : ACT-064992D
INN of investigational material : -
Therapeutic category code : 219 Other cardiovascular agents
Dosage and Administration for Investigational
Sponsors
Janssen Pharmaceutical K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed and dated informed consent form (ICF). - Confirmed diagnosis of symptomatic PAH in WHO FC II or III. - Symptomatic PAH belonging to one of the following subgroups of WHO Group 1 pulmonary hypertension: > Idiopathic. > Heritable. > Drug- or toxin-induced. > Associated with connective tissue disease, HIV infection, portal hypertension or congenital heart disease with simple systemic-to-pulmonary shunt with persistent pulmonary hypertension documented by a right heart catheterization (RHC) >= 1 year after surgical repair. - PAH diagnosis confirmed by hemodynamic evaluation at rest (through central reading), evaluated within 5 weeks prior to randomization: > mean pulmonary artery pressure (mPAP) >= 25mmHg, AND > Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) = Pulmonary vascular resistance (PVR) >= 3 WU (i.e., >= 240 dyn*sec*cm-5) - Negative vasoreactivity test in idiopathic, heritable, and drug/toxin-induced PAH. (Participants for whom no vasoreactivity test was performed at diagnosis can be eligible if currently treated with PAH therapy for more than 3 months and PAH diagnosis confirmed by hemodynamic evaluation at least 3 months after introduction of their PAH therapy). - Currently receiving a stable dose of ERA or PDE-5i monotherapy for at least 3 months prior to baseline RHC, within the prespecified doses in the study protocol or no history of PAH-specific treatment. - Participant able to perform the 6MWT with a minimum distance of 100 m and maximum distance of 450 m at Screening. - A woman of childbearing potential must: > have negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization. > agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. > agree to follow the contraception scheme from Screening up to at least 30 days after study treatment discontinuation.
Exclusion criteria
Exclusion criteria: - Treatment with a soluble guanylate cyclase stimulator, L-arginine, any form of prostanoids or prostacyclinreceptor agonists (including oral, inhaled, or infused routes) in the 3-month period prior to start of treatment. - Treatment with combination therapy of ERA and PDE- 5i in the 3-month period prior to start of treatment or history of intolerance to ERA and PDE-5i combination therapy. - Hypersensitivity to any of the study treatments or any excipient of their formulations. - Treatment with a strong cytochrome P450 3A4 (CYP3A4) inducer in the 1-month period prior to start of treatment. - Treatment with a strong CYP3A4 inhibitor or a moderate dual CYP3A4/CYP2C9 inhibitor or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors in the 1- month period prior to start of treatment. - Treatment with doxazosin. - Treatment with any form of organic nitrate, either regularly or intermittently - Diuretic treatment initiated or dose changed within 1 week prior to the RHC or start of treatment. - Treatment with another investigational drug in the 3- month period prior to start of treatment. - Body mass index (BMI) > 40 kg/m2 at Screening. - Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at Screening: > BMI > 30 kg/m2. > Diabetes mellitus of any type. > Essential hypertension (even if well controlled). > Coronary artery disease, i.e. history of stable angina or known more than 50% stenosis in a coronary artery or history of myocardial infarction or history of or planned coronary artery bypass grafting and/or coronary artery stenting. - Known presence of moderate or severe obstructive lung disease any time prior to Screening as specified in study protocol. - Known presence of moderate or severe restrictive lung disease any time prior to Screening as specified in study protocol. - Clinically significant aortic or mitral valve disease; pericardial constriction; restrictive or congestive leftsided cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction; or left ventricular outflow obstruction, in the opinion of the investigator. - Known permanent atrial fibrillation, in the opinion of the investigator. - Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism). - Documented pulmonary veno-occlusive disease. - Hemoglobin 1.5 * upper limit of normal (ULN) at Screening. - Severe renal impairment at Screening as specified in study protocol. - Systemic hypotension at Screening or Randomization and systemic hypertension at Screening as specified in study protocol. - Acute myocardial infarction or cerebrovascular event (e.g., stroke) within the last 26 weeks prior to Screening. - Known bleeding disorder, in the opinion of the investigator - Loss of vision in one or both eyes because of nonarteritic anterior ischemic optic neuropathy - Hereditary degenerative retinal disorders, including retinitis pigmentosa. - Difficulty swallowing large pills/tablets that would interfere with the ability to comply with study treatment regimen. - Any planned surgical intervention (including organ transplant) during the double-blind treatment period, except minor interventions. - Exercise training program for cardiopulmonary rehabil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Change in Pulmonary Vascular Resistance (PVR) expressed as the ratio of geometric means of End of Double-Blind Treatment (EDBT) to baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Change in 6-minute walk distance (6MWD) from baseline to EDBT efficacy Change From Baseline in Cardiopulmonary Symptom Domain Score in PAH-SYMPACT to Week 16 efficacy Change From Baseline in Cardiovascular Symptom Domain Score in PAH-SYMPACT to Week 16 efficacy Proportion of subjects with absence of worsening in World Health Organization (WHO) Functional Class (FC) from baseline to EDBT. | — |
Countries
Europe, Japan, South America
Contacts
Public ContactMedical Information Center
Janssen Pharmaceutical K.K.
Outcome results
None listed