Pulmonary Hypertension
Conditions
Keywords
Pulmonary arterial hypertension, PH, Stimulator
Brief summary
The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521 given orally for 12 weeks, in patients with symptomatic Pulmonary Arterial Hypertension (PAH).
Interventions
DRUGRiociguat (Adempas, BAY63-2521)
BAY63-2521: 1mg tid - 2.5mg tid orally for 12 weeks
DRUGPlacebo
Matching Placebo tid orally for 12 weeks
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients with symptomatic PAH (Idiopathic, Familial, Associated PAH due to connective tissue disease, congenital heart disease, portal hypertension with liver cirrhosis, or due to anorexigen or amphetamine use) * Treatment naive patients and patients pre-treated with an Endothelin Antagonist or a Prostacyclinanalogue (except I.V.).
Exclusion criteria
* All types of pulmonary hypertension except subtypes of Venice Group I specified in the inclusion criteria, severe COPD (chronic obstructive pulmonary disease), uncontrolled arterial hypertension, left heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12 | Baseline and week 12 | 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12 | Baseline and week 12 | N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure. |
| World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | Baseline and week 12 | The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH. |
| Percentage of Participants With Clinical Worsening | At week 12 | 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 . |
| Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 | Baseline and week 12 | The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80\*(PAPmean - PCWP)/CO |
| EQ-5D Utility Score - Change From Baseline to Week 12 | Baseline and week 12 | EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions). |
| Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12 | Baseline and week 12 | The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst). |
| Borg CR 10 Scale - Change From Baseline to Week 12 | Baseline and week 12 | The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 (Nothing at all) to 10 (Extremely strong - Maximal). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, New Zealand, Poland, Portugal, Russia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT 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 | 254 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT 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 | 63 |
| Placebo Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks | 126 |
| Total | 443 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow-up Period (FUP) | Adverse Event | 3 | 1 | 1 |
| Follow-up Period (FUP) | Death | 2 | 0 | 1 |
| Follow-up Period (FUP) | Lost to Follow-up | 1 | 0 | 2 |
| Follow-up Period (FUP) | Protocol Violation | 0 | 1 | 0 |
| Follow-up Period (FUP) | Withdrawal by Subject | 2 | 1 | 0 |
| Treatment Period | Adverse Event | 8 | 1 | 7 |
| Treatment Period | Death | 0 | 1 | 2 |
| Treatment Period | Lack of Efficacy | 0 | 0 | 1 |
| Treatment Period | Lost to Follow-up | 1 | 0 | 0 |
| Treatment Period | Non-compliance | 1 | 0 | 0 |
| Treatment Period | Not treated | 0 | 1 | 1 |
| Treatment Period | Protocol Violation | 1 | 2 | 2 |
| Treatment Period | Withdrawal by Subject | 6 | 2 | 3 |
Baseline characteristics
| Characteristic | Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 51.1 Years STANDARD_DEVIATION 16.6 | 48.8 Years STANDARD_DEVIATION 16.1 | 50.7 Years STANDARD_DEVIATION 16.5 | 50.6 Years STANDARD_DEVIATION 16.5 |
| Baseline 6MWD | 361.4 meters STANDARD_DEVIATION 67.7 | 363.2 meters STANDARD_DEVIATION 66.6 | 367.8 meters STANDARD_DEVIATION 74.6 | 363.5 meters STANDARD_DEVIATION 69.5 |
| BMI | 25.91 kg/m^2 STANDARD_DEVIATION 5.48 | 26.85 kg/m^2 STANDARD_DEVIATION 5.35 | 26.26 kg/m^2 STANDARD_DEVIATION 5.92 | 26.14 kg/m^2 STANDARD_DEVIATION 5.59 |
| PAH subtype Anorexigen or Amphtamin assoc: PAH | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| PAH subtype Congenital heart disease (operated) assoc. PAH | 15 Participants | 8 Participants | 12 Participants | 35 Participants |
| PAH subtype Connective tissue disease assoc. PAH | 71 Participants | 15 Participants | 25 Participants | 111 Participants |
| PAH subtype Familial PAH | 7 Participants | 1 Participants | 1 Participants | 9 Participants |
| PAH subtype Idiopathic PAH | 149 Participants | 39 Participants | 84 Participants | 272 Participants |
| PAH subtype Portal Pulmonary hypertension | 11 Participants | 0 Participants | 2 Participants | 13 Participants |
| pre-treated with endothelin receptor antagonist No | 141 Participants | 36 Participants | 72 Participants | 249 Participants |
| pre-treated with endothelin receptor antagonist Yes | 113 Participants | 27 Participants | 54 Participants | 194 Participants |
| pre-treated with prostacyclin analogue No | 234 Participants | 59 Participants | 119 Participants | 412 Participants |
| pre-treated with prostacyclin analogue Yes | 20 Participants | 4 Participants | 7 Participants | 31 Participants |
| Prior PH therapy Pre-Treated | 131 Participants | 31 Participants | 60 Participants | 222 Participants |
| Prior PH therapy Therapy-Naive | 123 Participants | 32 Participants | 66 Participants | 221 Participants |
| Pulmonary vascular resistance | 790.96 dn*s*cm^-5 STANDARD_DEVIATION 452.6 | 847.81 dn*s*cm^-5 STANDARD_DEVIATION 548.17 | 834.06 dn*s*cm^-5 STANDARD_DEVIATION 476.71 | 810.89 dn*s*cm^-5 STANDARD_DEVIATION 473.45 |
| Race/Ethnicity, Customized Asian | 79 Participants | 22 Participants | 38 Participants | 139 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not reported | 9 Participants | 7 Participants | 8 Participants | 24 Participants |
| Race/Ethnicity, Customized White | 161 Participants | 33 Participants | 78 Participants | 272 Participants |
| Sex: Female, Male Female | 203 Participants | 49 Participants | 98 Participants | 350 Participants |
| Sex: Female, Male Male | 51 Participants | 14 Participants | 28 Participants | 93 Participants |
| WHO (World Health Organization) functional class I | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| WHO (World Health Organization) functional class II | 108 Participants | 19 Participants | 60 Participants | 187 Participants |
| WHO (World Health Organization) functional class III | 140 Participants | 39 Participants | 58 Participants | 237 Participants |
| WHO (World Health Organization) functional class IV | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| WHO (World Health Organization) functional class missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 216 / 254 | 57 / 63 | 96 / 126 |
| serious Total, serious adverse events | 29 / 254 | 11 / 63 | 23 / 126 |
Outcome results
Primary
6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12
6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
Time frame: Baseline and week 12
Population: Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12 | 29.6 Meters | Standard Deviation 65.8 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12 | 31.1 Meters | Standard Deviation 79.3 |
| Placebo | 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12 | -5.6 Meters | Standard Deviation 85.5 |
Comparison: 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 significantp-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: <0.000195% CI: [20.06, 51.51]ANCOVA
Comparison: Shapiro-Wilk test for normality of ANCOVA residuals.p-value: 0.0001Shapiro-Wilk
Secondary
Borg CR 10 Scale - Change From Baseline to Week 12
The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 (Nothing at all) to 10 (Extremely strong - Maximal).
Time frame: Baseline and week 12
Population: Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Borg CR 10 Scale - Change From Baseline to Week 12 | -0.44 Scores on a scale | Standard Deviation 1.72 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Borg CR 10 Scale - Change From Baseline to Week 12 | -0.33 Scores on a scale | Standard Deviation 1.47 |
| Placebo | Borg CR 10 Scale - Change From Baseline to Week 12 | 0.09 Scores on a scale | Standard Deviation 2.05 |
Comparison: 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.p-value: 0.0022Wilcoxon (Mann-Whitney)
Secondary
EQ-5D Utility Score - Change From Baseline to Week 12
EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).
Time frame: Baseline and week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | EQ-5D Utility Score - Change From Baseline to Week 12 | 0.0329 Scores on a scale | Standard Deviation 0.235 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | EQ-5D Utility Score - Change From Baseline to Week 12 | 0.0782 Scores on a scale | Standard Deviation 0.3111 |
| Placebo | EQ-5D Utility Score - Change From Baseline to Week 12 | -0.0317 Scores on a scale | Standard Deviation 0.3044 |
Comparison: 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.p-value: 0.0663Wilcoxon (Mann-Whitney)
p-value: 0.019795% CI: [0.01, 0.11]ANCOVA
Comparison: Shapiro-Wilk test for normality of ANCOVA residuals.p-value: 0.0001Shapiro-Wilk
Secondary
Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12
The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).
Time frame: Baseline and week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12 | -5.99 Scores on a scale | Standard Deviation 17.76 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12 | -10.21 Scores on a scale | Standard Deviation 21.27 |
| Placebo | Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12 | 0.36 Scores on a scale | Standard Deviation 18.15 |
Comparison: 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.p-value: 0.0019Wilcoxon (Mann-Whitney)
p-value: 0.000995% CI: [-9.79, -2.54]ANCOVA
Comparison: Shapiro-Wilk test for normality of ANCOVA residuals.p-value: 0.0001Shapiro-Wilk
Secondary
N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12
N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.
Time frame: Baseline and week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12 | -197.89 pg/mL | Standard Deviation 1721.29 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12 | -471.50 pg/mL | Standard Deviation 913.02 |
| Placebo | N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12 | 232.39 pg/mL | Standard Deviation 1011.09 |
Comparison: Missing values at week 12 were imputed using the last available post-baseline observation. Same analysis method as for primary efficacy parameter.p-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: 0.015795% CI: [-781.52, -82.1]ANCOVA
Comparison: Shapiro-Wilk test for normality of ANCOVA residuals.p-value: 0.0001Shapiro-Wilk
Secondary
Percentage of Participants With Clinical Worsening
The combined endpoint time to clinical worsening, made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; atrial septostomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH .
Time frame: At week 12
Population: Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Any event | 1.2 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Decrease in 6MWT due to pulmonary hypertension | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Persistant worsening of functional class due to PH | 0 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Percentage of Participants With Clinical Worsening | Death | 0.8 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Death | 1.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Any event | 3.2 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Decrease in 6MWT due to pulmonary hypertension | 1.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Persistant worsening of functional class due to PH | 0 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 0 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Percentage of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 1.6 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 3.2 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 4.0 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Death | 2.4 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Decrease in 6MWT due to pulmonary hypertension | 1.6 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Any event | 6.3 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | Persistant worsening of functional class due to PH | 0.8 Percentage of participants |
Comparison: The test is for difference of occurence of Any event.p-value: 0.004695% CI: [-9.85, -0.55]Log Rank
Secondary
Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12
The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80\*(PAPmean - PCWP)/CO
Time frame: Baseline and week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 | -223.29 dyn*s*cm^-5 | Standard Deviation 260.09 |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 | -167.79 dyn*s*cm^-5 | Standard Deviation 320.22 |
| Placebo | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 | -8.89 dyn*s*cm^-5 | Standard Deviation 316.57 |
Comparison: Missing values at week 12 were imputed using the last available post-baseline observation. Same analysis method as for primary efficacy parameter.p-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: <0.000195% CI: [-281.37, -170.08]ANCOVA
Comparison: Shapiro-Wilk test for normality of ANCOVA residuals.p-value: 0.0001Shapiro-Wilk
Secondary
World Health Organization (WHO) Functional Class - Change From Baseline to Week 12
The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.
Time frame: Baseline and week 12
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -2 | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -1 | 20.5 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 0 | 75.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 1 | 2.8 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 2 | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 3 | 0.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 3 | 0 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -2 | 0 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 1 | 6.3 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 2 | 1.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -1 | 23.8 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 0 | 68.3 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -1 | 14.4 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 0 | 71.2 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 3 | 0 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 1 | 12.0 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | -2 | 0 Percentage of participants |
| Placebo | World Health Organization (WHO) Functional Class - Change From Baseline to Week 12 | 2 | 2.4 Percentage of participants |
Comparison: 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.p-value: 0.0033Wilcoxon (Mann-Whitney)