Patients symptomatic with pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD) MedDRA version: 21.1 Level: LLT Classification code 10037406 Term: Pulmonary hypertension secondary System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Adempas
Product Name: Adempas 0.5 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 18 to 80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.) • Male and female subjects with symptomatic PH-sLVD (group 2 / 2.1 of Dana Point Classification and World Health Organization [WHO] class II-IV) due to ischemic heart disease or dilated cardiomyopathy (DCM). Transplant candidates can be included. (Other groups of pulmonary hypertension, especially CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.) PH-sLVD is defined as: • LVEF = 40%, diagnosed by echocardiography, radionuclide ventriculography or left heart catheter (LHC) exam within 30 days before randomization, or in the baseline echocardiography (Note: the definition of PH-sLVD was changed in amendment 3 see section 13.2.1.2) • PAPmean = 25 mmHg at rest, measured by right heart catheter (RHC) • Subjects must be pre treated and individually maximally titrated with optimized CHF therapy according to European Society of Cardiology (ESC) (9), American College of Cardiology/American Heart Association (ACC/AHA) (10) or Japanese Circulation Society (11) guidelines with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta blockers and mineralocorticoid receptor (MR) antagonists as clinically indicated. The dose regimen must have been stable for > 30 days prior to randomization. Diuretic therapy must have been stable for = 1 week before performing baseline RHC. • RHC results for the definite diagnosis of PH not older than 1 week at Visit 1. RHC must have been performed in the participating centre under standardized conditions (refer to the study specific right heart catheterization manual). • Left heart catheter results available any time prior to randomization to judge if left-heart disease is caused by ischemic heart disease or dilated cardiomyopathy • A negative stress test must have been performed =65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: • PH in groups other than group 2.1 according to Dana Point classification (2). In particular, CTEPH must have been ruled out according to accepted diagnostic procedures and guidelines. • Cardiac decompensation, either with hospitalization or visit to the emergency department, = 30 days prior to randomization • Resynchronization therapy initiated = 90 days prior to randomization • Need of intravenous (IV) diuretics = 30 days prior to randomization • Treatment with IV inotropes or IV vasodilators = 30 days prior to randomization • Chronic treatment with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 (PDE5) inhibitors or prostanoids = 30 days prior to randomization, or with nitrates = 7 days prior to randomization (PDE5 inhibitors = 7 days prior to randomization if indicated for erectile dysfunction) • Subjects who medically require treatment with drugs that are not in line with the in or exclusion criteria of this study or that are prohibited concomitant medications (see section 6.9) for this study • Bronchial asthma or chronic obstructive pulmonary disease (COPD) with forced expiratory volume in one second (FEV1) 180 mmHg or diastolic blood pressure [DBP] > 110 mmHg) • SBP 105 BPM (in case of atrial fibrillation > 110 BPM) • Investigational treatment in another clinical trial during the preceding 30 days • Subjects with a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the subject’s ability to participate or complete the 4 month main study • Subjects with underlying medical disorders with an anticipated life expectancy below 2 years not due to cardiac conditions (e.g. active cancer disease with localized and/or metastasized tumor mass) • Subjects with a history of multiple drug allergies • Subjects with hypersensitivity to the in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the hemodynamic profile of Riociguat in patients with symptomatic pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD). ;Secondary Objective: The secondary objectives of this study are to assess safety, tolerability and pharmacokinetic profile of Riociguat in patients with symptomatic pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD), and to explore doses and potential endpoints for phase III ;Primary end point(s): The primary efficacy endpoint will be the change from baseline to week 16 in PAPmean at rest.. ;Timepoint(s) of evaluation of this end point: From baseline to week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Italy, Japan, Netherlands, Poland, Singapore, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed