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A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH) (PATENT-1)

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ClinicalTrials.gov Identifier: NCT00810693
Recruitment Status : Completed
First Posted : December 18, 2008
Results First Posted : February 26, 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 445
Recruitment Details Only participants with symptomatic Pulmonary arterial hypertension (PAH) could participate in this study. Both treatment-naïve participants and participants pre-treated with an endothelin receptor antagonist or a non-intravenous prostacyclin analogue could be included.
Pre-assignment Details 586 participants were enrolled in 124 study centers in 30 countries worldwide. 141 of the 586 enrolled participants were not randomized (adverse event [4], protocol violation [129], withdrawal by subject [8]). 445 of the 586 participants were randomized. 443 of the 445 randomized participants received study medication.
Arm/Group Title Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks 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 Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Period Title: Treatment Period
Started 254 64 [1] 127 [1]
Participants Received Treatment 254 63 126
Completed 237 57 111
Not Completed 17 7 16
Reason Not Completed
Adverse Event             8             1             7
Death             0             1             2
Lack of Efficacy             0             0             1
Lost to Follow-up             1             0             0
Non-compliance             1             0             0
Protocol Violation             1             2             2
Withdrawal by Subject             6             2             3
Not treated             0             1             1
[1]
1 randomized but not treated
Period Title: Follow-up Period (FUP)
Started 23 [1] 7 [1] 16 [1]
Completed 15 4 12
Not Completed 8 3 4
Reason Not Completed
Adverse Event             3             1             1
Death             2             0             1
Lost to Follow-up             1             0             2
Protocol Violation             0             1             0
Withdrawal by Subject             2             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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks 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 Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 254 63 126 443
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 254 participants 63 participants 126 participants 443 participants
51.1  (16.6) 48.8  (16.1) 50.7  (16.5) 50.6  (16.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
Female
203
  79.9%
49
  77.8%
98
  77.8%
350
  79.0%
Male
51
  20.1%
14
  22.2%
28
  22.2%
93
  21.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
White 161 33 78 272
Black or African American 4 1 1 6
Asian 79 22 38 139
Mixed 1 0 1 2
Not reported 9 7 8 24
Prior PH therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
Therapy-Naive 123 32 66 221
Pre-Treated 131 31 60 222
pre-treated with endothelin receptor antagonist   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
Yes 113 27 54 194
No 141 36 72 249
[1]
Measure Description: Subjects pre-treated with an endothelin receptor antagonist.
pre-treated with prostacyclin analogue   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
Yes 20 4 7 31
No 234 59 119 412
[1]
Measure Description: Subjects pre-treated with a prostacyclin analogue.
PAH subtype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
Idiopathic PAH 149 39 84 272
Familial PAH 7 1 1 9
Connective tissue disease assoc. PAH 71 15 25 111
Congenital heart disease (operated) assoc. PAH 15 8 12 35
Portal Pulmonary hypertension 11 0 2 13
Anorexigen or Amphtamin assoc: PAH 1 0 2 3
[1]
Measure Description: Subtypes acc. to the Venice Clinical Classification of PH, Group 1 (idiopathic PAH, familial PAH, associated PAH due to [1] connective tissue disease, [2] congenital heart disease, [3] portal hypertension with liver cirrhosis, or [4] anorexigen or amphetamine use)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 254 participants 63 participants 126 participants 443 participants
25.91  (5.48) 26.85  (5.35) 26.26  (5.92) 26.14  (5.59)
Baseline 6MWD   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 254 participants 63 participants 126 participants 443 participants
361.4  (67.7) 363.2  (66.6) 367.8  (74.6) 363.5  (69.5)
[1]
Measure Description: 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
WHO (World Health Organization) functional class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 63 participants 126 participants 443 participants
I 5 5 4 14
II 108 19 60 187
III 140 39 58 237
IV 1 0 3 4
missing 0 0 1 1
[1]
Measure Description: 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.
Pulmonary vascular resistance   [1] 
Mean (Standard Deviation)
Unit of measure:  Dn*s*cm^-5
Number Analyzed 254 participants 63 participants 126 participants 443 participants
790.96  (452.60) 847.81  (548.17) 834.06  (476.71) 810.89  (473.45)
[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 12
Hide Description 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
Time Frame Baseline and week 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 254 63 126
Mean (Standard Deviation)
Unit of Measure: Meters
29.6  (65.8) 31.1  (79.3) -5.6  (85.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments Missing values for participants who withdrew/died before 12 weeks were imputed with worst value of 0m in case of death or clinical worsening without termination visit and with last observed value otherwise. Comparison was done using ANCOVA, with baseline 6MWD as a covariate and treatment group, region and treatment naive/add-on therapy 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 and therapy naive/add-on therapy
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 35.78
Confidence Interval (2-Sided) 95%
20.06 to 51.51
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12
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 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 232 58 107
Mean (Standard Deviation)
Unit of Measure: dyn*s*cm^-5
-223.29  (260.09) -167.79  (320.22) -8.89  (316.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments Missing values at week 12 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, TTCW, Borg scale, EQ5D, LPH. Primary analysis due to result of Shapiro-Wilk test.
Method Wilcoxon (Mann-Whitney)
Comments Test was stratified by region and therapy naive/add-on therapy
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 -225.72
Confidence Interval (2-Sided) 95%
-281.37 to -170.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12
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 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 228 54 106
Mean (Standard Deviation)
Unit of Measure: pg/mL
-197.89  (1721.29) -471.50  (913.02) 232.39  (1011.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments Missing values at week 12 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 Test was stratified by region and therapy naive/add-on therapy
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0157
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 -431.81
Confidence Interval (2-Sided) 95%
-781.52 to -82.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12
Hide Description 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.
Time Frame Baseline and week 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 254 63 125
Measure Type: Number
Unit of Measure: Percentage of participants
-2 0.4 0 0
-1 20.5 23.8 14.4
0 75.6 68.3 71.2
1 2.8 6.3 12.0
2 0.4 1.6 2.4
3 0.4 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments Missing values for participants who withdrew or died before 12 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 0.0033
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 and therapy naive/add-on therapy
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; 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 .
Time Frame At week 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 254 63 126
Measure Type: Number
Unit of Measure: Percentage of participants
Any event 1.2 3.2 6.3
Hospitalization due to pulmonary hypertension 0.4 0 3.2
Start of new pulmonary hypertension treatment 0.4 1.6 4.0
Decrease in 6MWT due to pulmonary hypertension 0.4 1.6 1.6
Persistant worsening of functional class due to PH 0 0 0.8
Death 0.8 1.6 2.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments The test is for difference of occurence of "Any event".
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
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 and therapy naive/add-on therapy
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -5.20
Confidence Interval (2-Sided) 95%
-9.85 to -0.55
Estimation Comments Based on Mantel-Haenszel estimate stratified by region and therapy naive/add-on therapy.
6.Secondary Outcome
Title Borg CR 10 Scale - Change From Baseline to Week 12
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 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 254 63 126
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.44  (1.72) -0.33  (1.47) 0.09  (2.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments Missing values for participants who withdrew or died before 12 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 0.0022
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 and therapy naive/add-on therapy
7.Secondary Outcome
Title EQ-5D Utility Score - Change From Baseline to Week 12
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 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 253 62 124
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
0.0329  (0.2350) 0.0782  (0.3111) -0.0317  (0.3044)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12 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 0.0663
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 Test was stratified by region and therapy naive/add-on therapy.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0197
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 0.06
Confidence Interval (2-Sided) 95%
0.01 to 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12
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 12
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks
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
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Overall Number of Participants Analyzed 247 62 122
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-5.99  (17.76) -10.21  (21.27) 0.36  (18.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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 12 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 0.0019
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 Test was stratified by region and therapy naive/add-on therapy.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
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 -6.17
Confidence Interval (2-Sided) 95%
-9.79 to -2.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT, 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]
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 12 weeks 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 Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
All-Cause Mortality
Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   29/254 (11.42%)   11/63 (17.46%)   23/126 (18.25%) 
Blood and lymphatic system disorders       
Anaemia * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Cardiac disorders       
Atrioventricular block * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Cardiac failure * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Cardiomegaly * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Right ventricular failure * 1  2/254 (0.79%)  3/63 (4.76%)  1/126 (0.79%) 
Supraventricular tachycardia * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Eye disorders       
Retinal artery occlusion * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Gastrointestinal disorders       
Abdominal pain * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Diarrhoea * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Gastritis * 1  1/254 (0.39%)  1/63 (1.59%)  0/126 (0.00%) 
Haematemesis * 1  0/254 (0.00%)  1/63 (1.59%)  0/126 (0.00%) 
Irritable bowel syndrome * 1  0/254 (0.00%)  1/63 (1.59%)  0/126 (0.00%) 
Intra-abdominal haemorrhage * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
General disorders       
Asthenia * 1  1/254 (0.39%)  0/63 (0.00%)  1/126 (0.79%) 
Chest pain * 1  2/254 (0.79%)  0/63 (0.00%)  1/126 (0.79%) 
Pyrexia * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Infections and infestations       
Bronchitis * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Bronchopneumonia * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Diarrhoea infectious * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Encephalitis herpes * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Gastroenteritis * 1  1/254 (0.39%)  1/63 (1.59%)  0/126 (0.00%) 
Infection * 1  0/254 (0.00%)  1/63 (1.59%)  0/126 (0.00%) 
Influenza * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Pneumonia * 1  2/254 (0.79%)  1/63 (1.59%)  0/126 (0.00%) 
Sepsis * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Tooth infection * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Enterocolitis infectious * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Mycoplasma infection * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Respiratory tract infection * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Injury, poisoning and procedural complications       
Muscle rupture * 1  0/254 (0.00%)  1/63 (1.59%)  0/126 (0.00%) 
Overdose * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Subdural haematoma * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Investigations       
Catheterisation cardiac * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Electrocardiogram ST-T segment abnormal * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Hepatic enzyme increased * 1  1/254 (0.39%)  0/63 (0.00%)  1/126 (0.79%) 
Metabolism and nutrition disorders       
Dehydration * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastatic malignant melanoma * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Nervous system disorders       
Dizziness * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Loss of consciousness * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Presyncope * 1  1/254 (0.39%)  0/63 (0.00%)  1/126 (0.79%) 
Syncope * 1  3/254 (1.18%)  0/63 (0.00%)  5/126 (3.97%) 
Psychiatric disorders       
Anxiety * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Renal and urinary disorders       
Renal failure acute * 1  2/254 (0.79%)  0/63 (0.00%)  0/126 (0.00%) 
Reproductive system and breast disorders       
Vaginal haemorrhage * 1  0/254 (0.00%)  1/63 (1.59%)  0/126 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Haemoptysis * 1  2/254 (0.79%)  0/63 (0.00%)  0/126 (0.00%) 
Hypoxia * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Interstitial lung disease * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Pneumothorax * 1  1/254 (0.39%)  0/63 (0.00%)  1/126 (0.79%) 
Pulmonary congestion * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Pulmonary hypertension * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
Respiratory failure * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Pulmonary arterial hypertension * 1  1/254 (0.39%)  1/63 (1.59%)  2/126 (1.59%) 
Vascular disorders       
Circulatory collapse * 1  0/254 (0.00%)  0/63 (0.00%)  1/126 (0.79%) 
Hypotension * 1  1/254 (0.39%)  0/63 (0.00%)  0/126 (0.00%) 
*
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) up to 2.5 mg_IDT Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   216/254 (85.04%)   57/63 (90.48%)   96/126 (76.19%) 
Blood and lymphatic system disorders       
Anaemia * 1  20/254 (7.87%)  1/63 (1.59%)  3/126 (2.38%) 
Cardiac disorders       
Palpitations * 1  20/254 (7.87%)  5/63 (7.94%)  6/126 (4.76%) 
Tachycardia * 1  9/254 (3.54%)  0/63 (0.00%)  7/126 (5.56%) 
Gastrointestinal disorders       
Abdominal discomfort * 1  7/254 (2.76%)  0/63 (0.00%)  1/126 (0.79%) 
Abdominal distension * 1  6/254 (2.36%)  2/63 (3.17%)  1/126 (0.79%) 
Abdominal pain * 1  9/254 (3.54%)  0/63 (0.00%)  3/126 (2.38%) 
Abdominal pain upper * 1  9/254 (3.54%)  2/63 (3.17%)  5/126 (3.97%) 
Constipation * 1  9/254 (3.54%)  3/63 (4.76%)  2/126 (1.59%) 
Diarrhoea * 1  35/254 (13.78%)  6/63 (9.52%)  12/126 (9.52%) 
Dyspepsia * 1  48/254 (18.90%)  8/63 (12.70%)  10/126 (7.94%) 
Gastric polyps * 1  0/254 (0.00%)  2/63 (3.17%)  0/126 (0.00%) 
Gastritis * 1  3/254 (1.18%)  4/63 (6.35%)  0/126 (0.00%) 
Gastrooesophageal reflux disease * 1  14/254 (5.51%)  4/63 (6.35%)  4/126 (3.17%) 
Nausea * 1  40/254 (15.75%)  10/63 (15.87%)  16/126 (12.70%) 
Vomiting * 1  26/254 (10.24%)  7/63 (11.11%)  11/126 (8.73%) 
General disorders       
Asthenia * 1  6/254 (2.36%)  2/63 (3.17%)  2/126 (1.59%) 
Chest discomfort * 1  6/254 (2.36%)  4/63 (6.35%)  11/126 (8.73%) 
Chest pain * 1  16/254 (6.30%)  4/63 (6.35%)  10/126 (7.94%) 
Face oedema * 1  5/254 (1.97%)  1/63 (1.59%)  4/126 (3.17%) 
Fatigue * 1  7/254 (2.76%)  0/63 (0.00%)  8/126 (6.35%) 
Feeling hot * 1  2/254 (0.79%)  0/63 (0.00%)  3/126 (2.38%) 
Oedema * 1  8/254 (3.15%)  1/63 (1.59%)  2/126 (1.59%) 
Oedema peripheral * 1  44/254 (17.32%)  14/63 (22.22%)  14/126 (11.11%) 
Pyrexia * 1  7/254 (2.76%)  6/63 (9.52%)  4/126 (3.17%) 
Infections and infestations       
Bronchitis * 1  8/254 (3.15%)  3/63 (4.76%)  3/126 (2.38%) 
Gastroenteritis * 1  7/254 (2.76%)  0/63 (0.00%)  1/126 (0.79%) 
Nasopharyngitis * 1  26/254 (10.24%)  6/63 (9.52%)  14/126 (11.11%) 
Oral candidiasis * 1  0/254 (0.00%)  2/63 (3.17%)  0/126 (0.00%) 
Upper respiratory tract infection * 1  7/254 (2.76%)  2/63 (3.17%)  5/126 (3.97%) 
Urinary tract infection * 1  3/254 (1.18%)  0/63 (0.00%)  4/126 (3.17%) 
Respiratory tract infection * 1  7/254 (2.76%)  2/63 (3.17%)  5/126 (3.97%) 
Investigations       
Activated partial thromboplastin time prolonged * 1  3/254 (1.18%)  0/63 (0.00%)  3/126 (2.38%) 
Haemoglobin decreased * 1  0/254 (0.00%)  3/63 (4.76%)  0/126 (0.00%) 
International normalised ratio increased * 1  6/254 (2.36%)  0/63 (0.00%)  5/126 (3.97%) 
Metabolism and nutrition disorders       
Hyperuricaemia * 1  2/254 (0.79%)  2/63 (3.17%)  1/126 (0.79%) 
Hypokalaemia * 1  12/254 (4.72%)  3/63 (4.76%)  6/126 (4.76%) 
Iron deficiency * 1  1/254 (0.39%)  0/63 (0.00%)  3/126 (2.38%) 
Decreased appetite * 1  5/254 (1.97%)  1/63 (1.59%)  3/126 (2.38%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  8/254 (3.15%)  0/63 (0.00%)  3/126 (2.38%) 
Back pain * 1  9/254 (3.54%)  3/63 (4.76%)  4/126 (3.17%) 
Muscle spasms * 1  3/254 (1.18%)  1/63 (1.59%)  4/126 (3.17%) 
Musculoskeletal pain * 1  4/254 (1.57%)  0/63 (0.00%)  3/126 (2.38%) 
Myalgia * 1  2/254 (0.79%)  2/63 (3.17%)  1/126 (0.79%) 
Pain in extremity * 1  11/254 (4.33%)  0/63 (0.00%)  6/126 (4.76%) 
Nervous system disorders       
Dizziness * 1  39/254 (15.35%)  15/63 (23.81%)  15/126 (11.90%) 
Headache * 1  69/254 (27.17%)  20/63 (31.75%)  25/126 (19.84%) 
Presyncope * 1  4/254 (1.57%)  2/63 (3.17%)  0/126 (0.00%) 
Psychiatric disorders       
Anxiety * 1  2/254 (0.79%)  2/63 (3.17%)  2/126 (1.59%) 
Insomnia * 1  9/254 (3.54%)  1/63 (1.59%)  1/126 (0.79%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  12/254 (4.72%)  3/63 (4.76%)  13/126 (10.32%) 
Dyspnoea * 1  16/254 (6.30%)  4/63 (6.35%)  14/126 (11.11%) 
Epistaxis * 1  11/254 (4.33%)  1/63 (1.59%)  1/126 (0.79%) 
Nasal congestion * 1  11/254 (4.33%)  4/63 (6.35%)  3/126 (2.38%) 
Pharyngeal inflammation * 1  0/254 (0.00%)  2/63 (3.17%)  0/126 (0.00%) 
Oropharyngeal pain * 1  2/254 (0.79%)  0/63 (0.00%)  6/126 (4.76%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  2/254 (0.79%)  2/63 (3.17%)  1/126 (0.79%) 
Erythema * 1  3/254 (1.18%)  3/63 (4.76%)  0/126 (0.00%) 
Pruritus * 1  4/254 (1.57%)  2/63 (3.17%)  2/126 (1.59%) 
Vascular disorders       
Flushing * 1  5/254 (1.97%)  2/63 (3.17%)  7/126 (5.56%) 
Hypotension * 1  24/254 (9.45%)  2/63 (3.17%)  3/126 (2.38%) 
Hot flush * 1  1/254 (0.39%)  1/63 (1.59%)  6/126 (4.76%) 
*
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
Name/Title: Therapeutic Area Head
Organization: Bayer
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00810693     History of Changes
Other Study ID Numbers: 12934
2008-003482-68 ( EudraCT Number )
First Submitted: December 17, 2008
First Posted: December 18, 2008
Results First Submitted: November 5, 2013
Results First Posted: February 26, 2014
Last Update Posted: November 28, 2016