A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH)

Study Overview
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Brief Summary
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The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521 given orally for 12 weeks, in patients with symptomatic Pulmonary Arterial Hypertension (PAH).

Official Title
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Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Symptomatic Pulmonary Arterial Hypertension (PAH)

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Riociguat (Adempas, BAY63-2521)
* Drug: Riociguat (Adempas, BAY63-2521)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with symptomatic PAH (Idiopathic, Familial, Associated PAH due to connective tissue disease, congenital heart disease, portal hypertension with liver cirrhosis, or due to anorexigen or amphetamine use) Treatment naive patients and patients pre-treated with an Endothelin Antagonist or a Prostacyclinanalogue (except I.V.). Exclusion Criteria: All types of pulmonary hypertension except subtypes of Venice Group I specified in the inclusion criteria, severe COPD (chronic obstructive pulmonary disease), uncontrolled arterial hypertension, left heart failure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT<br>Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks | Drug: Riociguat (Adempas, BAY63-2521)<br>* BAY63-2521: 1mg tid - 2.5mg tid orally for 12 weeks<br>|
| Experimental: Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT<br>Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks | Drug: Riociguat (Adempas, BAY63-2521)<br>* BAY63-2521: 1.5mg tid orally for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks | Drug: Placebo<br>* Matching Placebo tid orally for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12 | 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 | The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80*(PAPmean - PCWP)/CO | Baseline and week 12 | 
| N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12 | N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure. | Baseline and week 12 | 
| World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH. | Baseline and week 12 | 
| Percentage of Participants With Clinical Worsening | The combined endpoint time to clinical worsening, made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; atrial septostomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH . | At week 12 | 
| Borg CR 10 Scale - Change From Baseline to Week 12 | The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 (Nothing at all) to 10 (Extremely strong - Maximal). | Baseline and week 12 | 
| EQ-5D Utility Score - Change From Baseline to Week 12 | EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions). | Baseline and week 12 | 
| Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12 | The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst). | Baseline and week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stimulator, PH, Pulmonary arterial hypertension