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A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1)

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ClinicalTrials.gov Identifier: NCT00855465
Recruitment Status : Completed
First Posted : March 4, 2009
Results First Posted : March 11, 2014
Last Update Posted : November 28, 2016
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Hypertension
Interventions Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo
Enrollment 262
Recruitment Details Only subjects with symptomatic chronic thromboembolic pulmonary hypertension (CTEPH) could participate in this study. CTEPH was defined either as inoperable or as persisting or recurrent PH after pulmonary endarterectomy.
Pre-assignment Details 446 subjects were screened in 89 study centers in 26 countries worldwide. 184 of the 446 screened subjects were not randomized (adverse event [1], death [4], protocol violation [164], withdrawal by subject [15]). 262 of the 446 subjects were randomized. 261 of the 262 randomized subjects received study medication.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description 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 16 weeks Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Period Title: Treatment Period
Started 174 88
Participants Received Treatment 173 [1] 88
Completed 160 83
Not Completed 14 5
Reason Not Completed
Adverse Event             4             2
Death             2             2
Lack of Efficacy             2             1
Non-compliance             1             0
Protocol Violation             2             0
Withdrawal by Subject             2             0
Not treated             1             0
[1]
1 subject randomized but not treated
Period Title: Follow-up Period (FUP)
Started 17 [1] 4 [1]
Completed 9 2
Not Completed 8 2
Reason Not Completed
Adverse Event             0             1
Death             0             1
Lost to Follow-up             3             0
Withdrawal by Subject             4             0
Missing             1             0
[1]
Started FUP only if prematurely withdrawn from trt period or if not entering LTE study.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo Total
Hide Arm/Group Description 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 16 weeks Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks Total of all reporting groups
Overall Number of Baseline Participants 173 88 261
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 173 participants 88 participants 261 participants
59.3  (13.9) 59.2  (12.7) 59.3  (13.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 173 participants 88 participants 261 participants
Female
118
  68.2%
54
  61.4%
172
  65.9%
Male
55
  31.8%
34
  38.6%
89
  34.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants 88 participants 261 participants
White 120 65 185
Black or African American 7 1 8
Asian 37 20 57
Mixed 1 0 1
Not reported 8 2 10
Operability   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants 88 participants 261 participants
Inoperable CTEPH 121 68 189
Postoperative CTEPH 52 20 72
[1]
Measure Description: CTEPH defined as inoperable or as persisting/recurrent PH after pulmonary endarterectomy (PEA).
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 173 participants 88 participants 261 participants
27.13  (5.75) 27.73  (5.30) 27.33  (5.60)
6-minute walking distance   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 173 participants 88 participants 261 participants
342.3  (81.9) 356.0  (74.7) 346.9  (79.7)
[1]
Measure Description: 6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.
WHO (World Health Organization) functional class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 173 participants 88 participants 261 participants
missing 0 1 1
I 3 0 3
II 55 25 80
III 107 60 167
IV 8 2 10
[1]
Measure Description: The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of pulmonary arterial hypertension (PAH).
Pulmonary vascular resistance   [1] 
Mean (Standard Deviation)
Unit of measure:  Dyn*s*cm^-5
Number Analyzed 173 participants 88 participants 261 participants
790.68  (431.57) 779.32  (400.94) 786.68  (420.21)
[1]
Measure Description: 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
1.Primary Outcome
Title 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16
Hide Description 6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Mean (Standard Deviation)
Unit of Measure: Meters
38.9  (79.3) -5.5  (84.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values for participants who withdrew/died before 16 weeks were imputed with a worst value of 0m in case of death/clinical worsening without termination visit and with the last observed value otherwise. Comparison was done using analysis of covariance (ANCOVA), with baseline 6MWD as a covariate and treatment group and region as main effects. The primary statistical method was the stratified Wilcoxon test if the Shapiro-Wilk test for normality of residuals was statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Prespecified significance level for all significance tests was 5%. Primary analysis, due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments Test was stratified by region.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Additional analysis, due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 45.69
Confidence Interval (2-Sided) 95%
24.74 to 66.63
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
2.Secondary Outcome
Title Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16
Hide Description 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
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one post-baseline measurement were included in the analysis of PVR.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 151 82
Mean (Standard Deviation)
Unit of Measure: dyn*s*cm^-5
-225.68  (247.52) 23.07  (273.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at week 16 were imputed using the last available post-baseline observation. Same analysis method as for primary efficacy parameter.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg scale, EQ5D, LPH. Primary analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Additional analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -246.43
Confidence Interval (2-Sided) 95%
-303.33 to -189.53
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
3.Secondary Outcome
Title N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16
Hide Description 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.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one post-baseline measurement were included in the analysis of NT-proBNP.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 150 73
Mean (Standard Deviation)
Unit of Measure: pg/mL
-290.69  (1716.90) 76.35  (1446.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at week 16 were imputed using the last available post-baseline observation. Same analysis method as for primary efficacy parameter.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg scale, EQ5D, LPH. Primary analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0293
Comments Additional analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -443.99
Confidence Interval (2-Sided) 95%
-842.95 to -45.03
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
4.Secondary Outcome
Title World Health Organization (WHO) Functional Class - Change From Baseline to Week 16
Hide Description The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients 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.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Participants with a missing baseline were excluded from the analysis of WHO functional class.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 87
Measure Type: Number
Unit of Measure: Percentage of Participants
-2 2.3 0
-1 30.6 14.9
0 61.8 78.2
1 4.0 3.4
2 0.6 3.4
3 0.6 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values for participants who withdrew or died before 16 weeks were imputed with a worst value of IV in case of clinical worsening without termination visit or measurement at that termination visit and with a worst value of V in case of death and with the last observed value otherwise.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg scale, EQ5D, LPH.
Method Wilcoxon (Mann-Whitney)
Comments Test was stratified by region.
5.Secondary Outcome
Title Percentage of Participants With Clinical Worsening
Hide Description The combined endpoint “time to clinical worsening”, made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; rescue endarterectomy; 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.
Time Frame At week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Measure Type: Number
Unit of Measure: Percentage of participants
Any Event 2.3 5.7
Hospitalization due to pulmonary hypertension 0 1.1
Start of new pulmonary hypertension 1.2 1.1
Decrease in 6MWT due to pulmonary hypertension 0.6 2.3
Persistant worsening of functional class due to PH 0 1.1
Death 1.2 3.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Test for difference of occurence of "Any event".
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1724
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg scale, EQ5D, LPH.
Method Log Rank
Comments Test was stratified by region.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -3.37
Confidence Interval (2-Sided) 95%
-8.72 to 1.99
Estimation Comments Based on Mantel-Haenszel estimate stratified by region.
6.Secondary Outcome
Title Borg CR 10 Scale - Change From Baseline to Week 16
Hide Description 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”).
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.83  (2.39) 0.17  (2.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values for participants who withdrew or died before 16 weeks were imputed with a worst value of 10 in case of death or clinical worsening without termination visit and with the last observed value otherwise.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg scale, EQ5D, LPH. Nominally significant only due to hierarchical testing.
Method Wilcoxon (Mann-Whitney)
Comments Test was stratified by region.
7.Secondary Outcome
Title EQ-5D Utility Score - Change From Baseline to Week 16
Hide Description 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).
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Participants with a missing baseline were excluded from the analysis of the EQ5D utility score.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 172 87
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
0.0615  (0.2768) -0.0819  (0.3446)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at baseline were imputed using last available observation prior to start of study treatment. Missing values for participants who withdrew or died before 16 weeks were imputed with a worst value of -0.594 in case of death or clinical worsening without termination visit and with the last observed value otherwise.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO FC, TTCW, Borg scale, EQ5D, LPH. Primary analysis due to result of Shapiro-Wilk test.Nominally significant only due to hierarchical testing.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Additional analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.06 to 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
8.Secondary Outcome
Title Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16
Hide Description 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).
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Participants with a missing baseline were excluded from the analysis of the LPH questionnaire.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 170 86
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-6.72  (18.62) -2.09  (19.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at baseline were imputed using last available observation prior to start of study treatment. Missing values for participants who withdrew or died before 16 weeks were imputed with a worst value of 105 in case of death or clinical worsening without termination visit and with the last observed value otherwise.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1220
Comments Hierarchical testing for secondary efficacy parameters in the order: PVR, NT-proBNP, WHO functional class, Time to clinical worsening, Borg Dyspnea Score, EQ5D, LPH. Primary analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0165
Comments Additional analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.76
Confidence Interval (2-Sided) 95%
-10.45 to -1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
9.Other Pre-specified Outcome
Title All Caused Mortality
Hide Description All cause mortality (including cardiovascular mortality) was one component of the composite endpoint "time to clinical worsening".
Time Frame At visit 6 (week 16)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - a randomized subject was valid for ITT analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Measure Type: Number
Unit of Measure: Participants
2 3
10.Other Pre-specified Outcome
Title Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16
Hide Description Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description

Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.

Only participants with a baseline and at least one post-baseline measurement were included in the analysis of PAPmean.

Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 156 84
Mean (Standard Deviation)
Unit of Measure: mmHg
-4.31  (6.70) 0.76  (7.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at week 16 were imputed using the last available post-baseline observation. Same analysis as for primary efficacy parameter.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Exploratory testing. Primary analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Additional analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.96
Confidence Interval (2-Sided) 95%
-6.75 to -3.16
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0231
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
11.Other Pre-specified Outcome
Title Cardiac Index (CI) - Change From Baseline to Week 16
Hide Description The cardiac index (CI) is a calculated hemodynamic parameter. CI is derived from the directly measured parameters cardiac output (CO), divided by the body surface area (BSA). BSA is a calculated parameter, using the subject’s height and weight in the DuBois formula. Formula: BSA = (W [kg]*0.425)*(H [cm]*0.725)*0.007184 (m^2)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description

Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.

Only participants with a baseline and at least one post-baseline measurement were included in the analysis of CI.

Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 155 83
Mean (Standard Deviation)
Unit of Measure: L/min/m^2
0.45  (0.56) -0.01  (0.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Missing values at week 16 were imputed using the last available post-baseline observation. Same analysis as for primary efficacy parameter.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Exploratory testing. Primary analysis due to result of Shapiro-Wilk test.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.33 to 0.62
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Additional analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521)_individual Dose Titration, Placebo
Comments Shapiro-Wilk test for normality of ANCOVA residuals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1160
Comments [Not Specified]
Method Shapiro-Wilk
Comments [Not Specified]
12.Other Pre-specified Outcome
Title Systolic Blood Pressure (SBP) - Change From Baseline to Week 16
Hide Description Systolic systemic arterial blood pressure (SBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 95 – 180 mmHg.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Mean (Standard Deviation)
Unit of Measure: mmHg
-10.49  (14.17) -5.28  (14.61)
13.Other Pre-specified Outcome
Title Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16
Hide Description Diastolic systemic arterial blood pressure (DBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: <= 110 mmHg.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Mean (Standard Deviation)
Unit of Measure: mmHg
-8.17  (10.81) -3.40  (10.38)
14.Other Pre-specified Outcome
Title Heart Rate (HR) - Change From Baseline to Week 16
Hide Description Heart rate (HR) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 50 -105 beats per minute (bpm) at rest.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 173 88
Mean (Standard Deviation)
Unit of Measure: Beats/min
0.83  (11.74) 1.67  (12.37)
15.Other Pre-specified Outcome
Title Alanine Aminotransferase (ALT) - Change From Baseline to Week 16
Hide Description Alanine Aminotransferase (ALT) is a standard clinical chemistry parameter. Normal range: 0 to 45 U/L.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 161 82
Mean (Standard Deviation)
Unit of Measure: U/L
-1.2  (16.2) 2.2  (13.6)
16.Other Pre-specified Outcome
Title Aspartate Aminotransferase (AST) - Change From Baseline to Week 16
Hide Description Aspartate Aminotransferase (AST) is a standard clinical chemistry parameter. Normal range: 0 to 41 U/L.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 160 82
Mean (Standard Deviation)
Unit of Measure: U/L
0.3  (14.4) 2.8  (12.0)
17.Other Pre-specified Outcome
Title Alkaline Phosphatase (AP) - Change From Baseline to Week 16
Hide Description Alkaline phosphatase (AP) is a standard clinical chemistry parameter. Normal range: 40 to 129 U/L (males), 35 to 104 U/L (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: U/L
-3.8  (19.4) 2.5  (20.2)
18.Other Pre-specified Outcome
Title Bilirubin - Change From Baseline to Week 16
Hide Description Bilirubin is a standard clinical chemistry parameter. Normal range: 0.1 to 1.2 mg/dL
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.010  (0.483) 0.189  (0.453)
19.Other Pre-specified Outcome
Title Creatinine - Change From Baseline to Week 16
Hide Description Creatinine is a standard clinical chemistry parameter. Normal range: 0.25 to 1.20 mg/dL (males), 0.46 to 1.00 mg/dL (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.003  (0.338) 0.032  (0.178)
20.Other Pre-specified Outcome
Title Creatinine Clearance - Change From Baseline to Week 16
Hide Description Creatinine clearance is a standard clinical chemistry parameter. Normal range: 90 to 140 mL/min (males), 80 to 125 mL/min (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: mL/min
2.25  (15.53) -0.93  (11.36)
21.Other Pre-specified Outcome
Title Creatine Kinase (CK) - Change From Baseline to Week 16
Hide Description Creatine Kinase is a standard clinical chemistry parameter. Normal range: 35 to 232 U/L (males), 26 to 145 U/L (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: U/L
7.9  (64.9) 5.6  (65.7)
22.Other Pre-specified Outcome
Title Erythrocytes (RBC) - Change From Baseline to Week 16
Hide Description Erythrocytes (red blood cells, RBC) is a standard clinical hematology parameter. Normal range: 4.6 to 5.8*10^12 cells/L (males), 4.1 to 5.2*10^12 cells/L (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 155 81
Mean (Standard Deviation)
Unit of Measure: *10^12 cells/L
-0.14  (0.39) 0.04  (0.31)
23.Other Pre-specified Outcome
Title Leukocytes (WBC) - Change From Baseline to Week 16
Hide Description Leukocytes (white blood cells, WBC) is a standard clinical hematology parameter. Normal range: 4.0 to 10.7*10^9 cells/L
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 155 81
Mean (Standard Deviation)
Unit of Measure: *10^9 cells/L
-0.55  (1.77) 0.23  (1.69)
24.Other Pre-specified Outcome
Title Lymphocytes - Change From Baseline to Week 16
Hide Description Total lymphocytes is a standard clinical hematology parameter. Normal range: 1.0 to 4.0*10^9 cells/L
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 154 79
Mean (Standard Deviation)
Unit of Measure: *10^9 cells/L
-0.16  (0.48) 0.00  (0.53)
25.Other Pre-specified Outcome
Title Neutrophils - Change From Baseline to Week 16
Hide Description Neutrophils is a standard clinical hematology parameter. Normal range: 1.6 to 7.4*10^9 cells/L
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 154 79
Mean (Standard Deviation)
Unit of Measure: *10^9 cells/L
-0.31  (1.55) 0.26  (1.57)
26.Other Pre-specified Outcome
Title Hemoglobin - Change From Baseline to Week 16
Hide Description Hemoglobin is a standard clinical hematology parameter. Normal range: 13.5 to 17.5 g/dL (males), 12.0 to 16.0 g/dL (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 155 81
Mean (Standard Deviation)
Unit of Measure: g/dL
-0.69  (1.17) 0.02  (0.88)
27.Other Pre-specified Outcome
Title Hematocrit - Change From Baseline to Week 16
Hide Description Hematocrit is a standard clinical hematology parameter. Normal range: 40 to 52% (males), 36 to 46% (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 155 81
Mean (Standard Deviation)
Unit of Measure: Volume percentage of red blood cells
-2.0  (4.1) 0.5  (3.5)
28.Other Pre-specified Outcome
Title Potassium - Change From Baseline to Week 16
Hide Description Potassium is a standard clinical chemistry parameter. Normal range: 3.5 to 5.3 mmol/L
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 161 82
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.08  (0.48) -0.02  (0.56)
29.Other Pre-specified Outcome
Title Urate - Change From Baseline to Week 16
Hide Description Urate is a standard clinical chemistry parameter. Normal range: 4.0 to 8.5 mg/dL (males, 16-59 years), 3.4 to 8.7 mg/dL (males, >60 years) 2.5 to 7.5 mg/dL (females)
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.405  (1.415) 0.209  (1.577)
30.Other Pre-specified Outcome
Title Urea (BUN) - Change From Baseline to Week 16
Hide Description Urea (blood urea nitrogen, BUN) is a standard clinical chemistry parameter. Normal range: 4 to 25 mg/dL
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.60  (15.26) 0.99  (13.62)
31.Other Pre-specified Outcome
Title Cystatin C - Change From Baseline to Week 16
Hide Description Cystatin C is a biomarker. Normal range: 0.53 to 1.01 ng/mL
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 139 66
Mean (Standard Deviation)
Unit of Measure: ng/ml
16.1  (241.1) 62.9  (198.0)
32.Other Pre-specified Outcome
Title Triacylglycerol Lipase - Change From Baseline to Week 16
Hide Description Triacylglycerol lipase is a standard clinical chemistry parameter. Normal range: 7 to 60 U/L
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of laboratory parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 82
Mean (Standard Deviation)
Unit of Measure: U/L
-4.2  (12.9) 0.1  (17.5)
33.Other Pre-specified Outcome
Title Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16
Hide Description Arterial partial pressure of carbon dioxide (PaCO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of blood gas parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 151 80
Mean (Standard Deviation)
Unit of Measure: mmHg
0.34  (4.05) 0.56  (4.52)
34.Other Pre-specified Outcome
Title Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16
Hide Description Arterial partial pressure of oxygen (PaO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of blood gas parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 151 80
Mean (Standard Deviation)
Unit of Measure: mmHg
-3.01  (14.71) -4.95  (12.05)
35.Other Pre-specified Outcome
Title Oxygen Saturation (SaO2) - Change From Baseline to Week 16
Hide Description Oxygen saturation (SaO2) is measured as part of the capillary or arterial blood gas analysis. Normal blood oxygen saturation is considered 95-100 percent. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of blood gas parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 151 79
Mean (Standard Deviation)
Unit of Measure: Percentage of oxygen saturation
-1.5  (4.4) -3.1  (8.0)
36.Other Pre-specified Outcome
Title Mean PR Duration (PRmean) - Change From Baseline to Week 16
Hide Description PR duration was evaluated as part of the 12-lead electrocardiogram. electrocardiograms (ECGs) were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 162 78
Mean (Standard Deviation)
Unit of Measure: ms
-0.32  (14.21) 0.87  (11.16)
37.Other Pre-specified Outcome
Title Mean QRS Duration (QRSmean) - Change From Baseline to Week 16
Hide Description QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 165 80
Mean (Standard Deviation)
Unit of Measure: ms
-0.19  (4.49) -0.05  (4.30)
38.Other Pre-specified Outcome
Title Mean QT Duration (QTmean) - Change From Baseline to Week 16
Hide Description QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 123 53
Mean (Standard Deviation)
Unit of Measure: ms
1.19  (24.89) -2.00  (25.56)
39.Other Pre-specified Outcome
Title Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16
Hide Description Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 123 53
Mean (Standard Deviation)
Unit of Measure: ms
-4.30  (14.44) -0.51  (15.58)
40.Other Pre-specified Outcome
Title Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16
Hide Description Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 123 53
Mean (Standard Deviation)
Unit of Measure: ms
-2.34  (13.71) -1.02  (13.29)
41.Other Pre-specified Outcome
Title Mean RR Duration (RRmean) - Change From Baseline to Week 16
Hide Description RR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 166 81
Mean (Standard Deviation)
Unit of Measure: ms
3.89  (132.02) -14.00  (131.93)
42.Other Pre-specified Outcome
Title Mean Ventricular Rate (VRmean) - Change From Baseline to Week 16
Hide Description Ventricular rate was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position
Time Frame Baseline and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety (SAF) - a randomized participant was valid for safety analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one measurement on treatment (or up to two days after stopping treatment) were included in the analysis of ECG parameters.
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description:
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 16 weeks
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Overall Number of Participants Analyzed 166 81
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
-0.70  (11.96) 1.60  (11.68)
Time Frame Adverse event data were collected after signing the informed consent until 2 days after end of study treatment over a period of approximately 30 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Hide Arm/Group Description 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 16 weeks Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
All-Cause Mortality
Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   34/173 (19.65%)   14/88 (15.91%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/173 (0.58%)  1/88 (1.14%) 
Cardiac disorders     
Atrial fibrillation * 1  1/173 (0.58%)  0/88 (0.00%) 
Atrial flutter * 1  1/173 (0.58%)  1/88 (1.14%) 
Atrial tachycardia * 1  1/173 (0.58%)  0/88 (0.00%) 
Cardiac arrest * 1  0/173 (0.00%)  2/88 (2.27%) 
Cardiac failure * 1  1/173 (0.58%)  0/88 (0.00%) 
Right ventricular failure * 1  6/173 (3.47%)  3/88 (3.41%) 
Sick sinus syndrome * 1  1/173 (0.58%)  0/88 (0.00%) 
Cardiopulmonary failure * 1  0/173 (0.00%)  1/88 (1.14%) 
Chronic right ventricular failure * 1  1/173 (0.58%)  0/88 (0.00%) 
Gastrointestinal disorders     
Duodenal ulcer * 1  1/173 (0.58%)  0/88 (0.00%) 
Gastric ulcer * 1  0/173 (0.00%)  1/88 (1.14%) 
Gastritis * 1  2/173 (1.16%)  0/88 (0.00%) 
Intestinal obstruction * 1  1/173 (0.58%)  0/88 (0.00%) 
General disorders     
Chest pain * 1  1/173 (0.58%)  0/88 (0.00%) 
General physical health deterioration * 1  1/173 (0.58%)  0/88 (0.00%) 
Oedema due to cardiac disease * 1  1/173 (0.58%)  0/88 (0.00%) 
Catheter site haemorrhage * 1  2/173 (1.16%)  0/88 (0.00%) 
Infections and infestations     
Bronchitis * 1  1/173 (0.58%)  1/88 (1.14%) 
Erysipelas * 1  1/173 (0.58%)  0/88 (0.00%) 
Gastroenteritis * 1  1/173 (0.58%)  0/88 (0.00%) 
Infection * 1  0/173 (0.00%)  1/88 (1.14%) 
Pneumonia * 1  1/173 (0.58%)  0/88 (0.00%) 
Anal abscess * 1  1/173 (0.58%)  0/88 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/173 (0.58%)  0/88 (0.00%) 
Head injury * 1  1/173 (0.58%)  0/88 (0.00%) 
Injury * 1  0/173 (0.00%)  1/88 (1.14%) 
Overdose * 1  1/173 (0.58%)  0/88 (0.00%) 
Investigations     
Light chain analysis increased * 1  0/173 (0.00%)  1/88 (1.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant * 1  1/173 (0.58%)  0/88 (0.00%) 
Nervous system disorders     
Syncope * 1  4/173 (2.31%)  3/88 (3.41%) 
Psychiatric disorders     
Bipolar I disorder * 1  0/173 (0.00%)  1/88 (1.14%) 
Renal and urinary disorders     
Renal failure * 1  1/173 (0.58%)  0/88 (0.00%) 
Renal failure acute * 1  1/173 (0.58%)  0/88 (0.00%) 
Renal failure chronic * 1  2/173 (1.16%)  0/88 (0.00%) 
Renal impairment * 1  0/173 (0.00%)  1/88 (1.14%) 
Reproductive system and breast disorders     
Vaginal haemorrhage * 1  1/173 (0.58%)  0/88 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/173 (0.58%)  0/88 (0.00%) 
Chronic obstructive pulmonary disease * 1  1/173 (0.58%)  1/88 (1.14%) 
Chronic respiratory failure * 1  1/173 (0.58%)  0/88 (0.00%) 
Dyspnoea * 1  1/173 (0.58%)  1/88 (1.14%) 
Haemoptysis * 1  3/173 (1.73%)  0/88 (0.00%) 
Pneumonitis * 1  1/173 (0.58%)  0/88 (0.00%) 
Pulmonary hypertension * 1  2/173 (1.16%)  0/88 (0.00%) 
Respiratory failure * 1  2/173 (1.16%)  0/88 (0.00%) 
Vascular disorders     
Hypotension * 1  1/173 (0.58%)  0/88 (0.00%) 
Deep vein thrombosis * 1  0/173 (0.00%)  1/88 (1.14%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Riociguat (Adempas, BAY63-2521)_individual Dose Titration Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   146/173 (84.39%)   67/88 (76.14%) 
Blood and lymphatic system disorders     
Anaemia * 1  5/173 (2.89%)  1/88 (1.14%) 
Cardiac disorders     
Bradycardia * 1  1/173 (0.58%)  2/88 (2.27%) 
Palpitations * 1  6/173 (3.47%)  4/88 (4.55%) 
Right ventricular failure * 1  2/173 (1.16%)  2/88 (2.27%) 
Ventricular extrasystoles * 1  0/173 (0.00%)  2/88 (2.27%) 
Ear and labyrinth disorders     
Vertigo * 1  1/173 (0.58%)  4/88 (4.55%) 
Gastrointestinal disorders     
Abdominal discomfort * 1  6/173 (3.47%)  2/88 (2.27%) 
Abdominal pain * 1  4/173 (2.31%)  0/88 (0.00%) 
Abdominal pain upper * 1  5/173 (2.89%)  3/88 (3.41%) 
Constipation * 1  10/173 (5.78%)  1/88 (1.14%) 
Diarrhoea * 1  17/173 (9.83%)  4/88 (4.55%) 
Dry mouth * 1  3/173 (1.73%)  2/88 (2.27%) 
Dyspepsia * 1  31/173 (17.92%)  7/88 (7.95%) 
Dysphagia * 1  6/173 (3.47%)  0/88 (0.00%) 
Gastritis * 1  6/173 (3.47%)  0/88 (0.00%) 
Gastrooesophageal reflux disease * 1  7/173 (4.05%)  0/88 (0.00%) 
Nausea * 1  19/173 (10.98%)  7/88 (7.95%) 
Vomiting * 1  17/173 (9.83%)  3/88 (3.41%) 
General disorders     
Asthenia * 1  3/173 (1.73%)  3/88 (3.41%) 
Chest discomfort * 1  5/173 (2.89%)  1/88 (1.14%) 
Chest pain * 1  6/173 (3.47%)  4/88 (4.55%) 
Fatigue * 1  5/173 (2.89%)  4/88 (4.55%) 
Oedema * 1  6/173 (3.47%)  2/88 (2.27%) 
Oedema peripheral * 1  27/173 (15.61%)  18/88 (20.45%) 
Pyrexia * 1  2/173 (1.16%)  2/88 (2.27%) 
Hepatobiliary disorders     
Hepatic function abnormal * 1  0/173 (0.00%)  2/88 (2.27%) 
Infections and infestations     
Bronchitis * 1  5/173 (2.89%)  2/88 (2.27%) 
Influenza * 1  0/173 (0.00%)  2/88 (2.27%) 
Nasopharyngitis * 1  26/173 (15.03%)  8/88 (9.09%) 
Rhinitis * 1  1/173 (0.58%)  2/88 (2.27%) 
Upper respiratory tract infection * 1  10/173 (5.78%)  4/88 (4.55%) 
Urinary tract infection * 1  7/173 (4.05%)  2/88 (2.27%) 
Respiratory tract infection * 1  4/173 (2.31%)  1/88 (1.14%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  8/173 (4.62%)  2/88 (2.27%) 
Blood bilirubin increased * 1  0/173 (0.00%)  2/88 (2.27%) 
Blood creatine phosphokinase increased * 1  2/173 (1.16%)  2/88 (2.27%) 
Blood creatinine increased * 1  3/173 (1.73%)  5/88 (5.68%) 
Blood potassium increased * 1  0/173 (0.00%)  2/88 (2.27%) 
Blood urea increased * 1  1/173 (0.58%)  3/88 (3.41%) 
Creatinine renal clearance decreased * 1  1/173 (0.58%)  3/88 (3.41%) 
Gamma-glutamyltransferase increased * 1  1/173 (0.58%)  2/88 (2.27%) 
International normalised ratio increased * 1  10/173 (5.78%)  4/88 (4.55%) 
Metabolism and nutrition disorders     
Gout * 1  0/173 (0.00%)  3/88 (3.41%) 
Hyperkalaemia * 1  3/173 (1.73%)  2/88 (2.27%) 
Hypokalaemia * 1  7/173 (4.05%)  2/88 (2.27%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  5/173 (2.89%)  1/88 (1.14%) 
Back pain * 1  7/173 (4.05%)  5/88 (5.68%) 
Joint swelling * 1  0/173 (0.00%)  2/88 (2.27%) 
Muscle spasms * 1  4/173 (2.31%)  2/88 (2.27%) 
Musculoskeletal pain * 1  5/173 (2.89%)  2/88 (2.27%) 
Myalgia * 1  4/173 (2.31%)  1/88 (1.14%) 
Pain in extremity * 1  3/173 (1.73%)  5/88 (5.68%) 
Musculoskeletal chest pain * 1  0/173 (0.00%)  2/88 (2.27%) 
Nervous system disorders     
Dizziness * 1  39/173 (22.54%)  11/88 (12.50%) 
Headache * 1  43/173 (24.86%)  12/88 (13.64%) 
Hypoaesthesia * 1  4/173 (2.31%)  1/88 (1.14%) 
Paraesthesia * 1  3/173 (1.73%)  3/88 (3.41%) 
Tremor * 1  2/173 (1.16%)  2/88 (2.27%) 
Restless legs syndrome * 1  1/173 (0.58%)  2/88 (2.27%) 
Psychiatric disorders     
Insomnia * 1  4/173 (2.31%)  6/88 (6.82%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  1/173 (0.58%)  2/88 (2.27%) 
Cough * 1  9/173 (5.20%)  16/88 (18.18%) 
Dyspnoea * 1  7/173 (4.05%)  11/88 (12.50%) 
Epistaxis * 1  2/173 (1.16%)  2/88 (2.27%) 
Nasal congestion * 1  6/173 (3.47%)  3/88 (3.41%) 
Productive cough * 1  3/173 (1.73%)  2/88 (2.27%) 
Skin and subcutaneous tissue disorders     
Eczema * 1  1/173 (0.58%)  2/88 (2.27%) 
Erythema * 1  1/173 (0.58%)  3/88 (3.41%) 
Hyperhidrosis * 1  1/173 (0.58%)  4/88 (4.55%) 
Vascular disorders     
Flushing * 1  7/173 (4.05%)  2/88 (2.27%) 
Haematoma * 1  2/173 (1.16%)  2/88 (2.27%) 
Hypotension * 1  15/173 (8.67%)  3/88 (3.41%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The embargo can be up to 6 months (equal to the 180 days), moreover if it is necessary the embargo period can be prolonged to expiry of priority year.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer
EMail: clinical-trials-contact@bayerhealthcare.com
Publications of Results:
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00855465     History of Changes
Other Study ID Numbers: 11348
2007-000072-16 ( EudraCT Number )
First Submitted: December 15, 2008
First Posted: March 4, 2009
Results First Submitted: November 4, 2013
Results First Posted: March 11, 2014
Last Update Posted: November 28, 2016