Pulmonary Hypertension
Conditions
Keywords
Chronic thromboembolic Hypertension, PH, soluble Guanylate Cyclase Stimulator, sGC
Brief summary
Patients who have completed the 16 weeks treatment of the CHEST-1 trial (study number 11348) will be asked to participate in this long term extension study with BAY63-2521. The aim of the long term study is to collect additional information to evaluate the safety and tolerability of BAY63-2521. Patients will be treated with open label medication on their individual optimal dose between 0,5 mg - 2,5 mg tid.
Interventions
DRUGRiociguat (Adempas, BAY63-2521)
BAY63-2521 - 1 mg tid - 2,5 mg tid orally until end of study
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have completed 16 weeks of treatment in the double blind trial CHEST 1
Exclusion criteria
* Patients who have an ongoing serious adverse event from CHEST 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years | Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication. |
| Number of Participants With Death | From baseline to end of safety follow-up visit, up to 10 years (1 month more than End of study visit) | Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | From baseline to Termination visit, up to 10 years | Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | From baseline to Termination visit, up to 10 years | Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change From Baseline of Hemoglobin in Hematology and Coagulation | From baseline to Termination visit, up to 10 years | Hemoglobin is standard Hematology and coagulation parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | From baseline to Termination visit, up to 10 years | Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | From baseline to Termination visit, up to 10 years | Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change From Baseline of Urate in Clinical Chemistry | From baseline to Termination visit, up to 10 years | Urate is standard clinical chemistry parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of Heart Rate | From baseline to Termination visit, up to 10 years | Heart rate was measured after the participant had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of Weight | From baseline to Termination visit, up to 10 years | Weight was evaluated for safety. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of Oxygen Saturation (SaO2) | From baseline to Termination visit, up to 10 years | SaO2 is one parameters of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of Arterial Partial Oxygen Pressure (PaO2) | From baseline to Termination visit, up to 10 years | PaO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | From baseline to Termination visit, up to 10 years | PaCO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of RR Duration From Electrocardiogram (ECG) | From baseline to Month 48 | Heart rate from ECG is derived from the RR duration, unless arrhythmias such as atrial fibrillation or ventricular extra beats require additional calculations. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set. |
| Change in World Health Organization (WHO) Functional Class | From baseline to End of study visit, up to 10 years | WHO classification: I: Participants with PH. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Participants with PH are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Participants with PH are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Participants with PH with inability to carry out any physical activity. They manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. For class change from baseline, minus indicates a participant's functional class decreased compared with baseline (e.g. -1 indicates a participant changed from class IV to class III, or from class II to class I), plus indicates a participant's functional class increased compared with baseline (e.g. +1 indicates a participant changed from class I to class II, or from class III to class IV). |
| Change of QRS Duration From ECG | From baseline to Month 48 | QRS duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set. |
| Change of QT Duration in ECG | From baseline to Month 48 | QT duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set. |
| Change in Six-minute Walking Distance (6MWD) Test | From baseline to End of study visit, up to 10 years | 6MWD is exercise testing and is one of efficacy evaluation |
| Change in Pulmonary Vascular Resistance (PVR) | From baseline to Month 45 and Month 48 | Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. Analyses up to Month 48 due to limited data. |
| Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | From baseline to End of study visit, up to 10 years | NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure |
| Change of PR Duration From ECG | From baseline to Month 48 | PR duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set. |
| Number of Participants With Clinical Worsening | From baseline to End of study visit, up to 10 years | Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH). |
| Incidence of Clinical Worsening Events Per 100 Person Years | From baseline to End of study visit, up to 10 years | Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH). |
| Change From Baseline in Borg CR 10 Scale | From baseline to Week 12 | The Borg CR10 Scale was measured in conjunction with the 6MWD test. The test was explained to the participant before starting the 6MWD test. Participants were asked to rank their exertion at the end of the 6MWD 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). |
| Change in Score of EQ-5D Questionnaire | From baseline to End of study visit, up to 10 years | The EQ-5D is a standardized instrument for use as a measure of health outcome. The EQ-5D is a self report questionnaire. 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). |
| Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | From baseline to End of study visit, up to 10 years | The LPH questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH is a self-report questionnaire and was completed by the participant. The LPH total score can range from 0 (best) to 105 (worst). |
| Change of Systolic Blood Pressure (SBP) | From baseline to Termination visit, up to 10 years | SBP was measured after the participant had been at rest for 10 minutes in a supine position. Low SBP was defined as SBP \<95 mmHg, normal SBP as SBP 95-140mmHg, and high SBP as SBP \>140 mmHg. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
| Change of Diastolic Blood Pressure (DBP) | From baseline to Termination visit, up to 10 years | DBP was measured after the participants had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Israel, Italy, Japan, Mexico, Poland, Portugal, Russia, Slovakia, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at 71 centers in 25 countries or regions, between 01-JUL-2009 (first participant first visit) and 19-AUG-2019 (last participant last visit)
Pre-assignment details
Of the 243 participants who completed CHEST-1 (NCT00855465), 237 entered CHEST-2. 155 participants were from the former riociguat treatment group, and 82 were from the former placebo group.
Participants by arm
| Arm | Count |
|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1. | 155 |
| Riociguat-Former Placebo Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day. | 82 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Death | 18 | 12 |
| Overall Study | Drug non-compliance | 1 | 0 |
| Overall Study | Lack of Efficacy | 4 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Riociguat-Former Riociguat 1.0-2.5 mg | Riociguat-Former Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 64 Participants | 32 Participants | 96 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants | 50 Participants | 141 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 13.8 | 59.2 years STANDARD_DEVIATION 12.4 | 59.1 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized Asian | 34 Participants | 19 Participants | 53 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Multiple races | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 105 Participants | 60 Participants | 165 Participants |
| Sex: Female, Male Female | 104 Participants | 49 Participants | 153 Participants |
| Sex: Female, Male Male | 51 Participants | 33 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 155 | 13 / 82 |
| other Total, other adverse events | 148 / 155 | 79 / 82 |
| serious Total, serious adverse events | 96 / 155 | 56 / 82 |
Outcome results
Primary
Number of Participants With Death
Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.
Time frame: From baseline to end of safety follow-up visit, up to 10 years (1 month more than End of study visit)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Death | 22 Participants |
| Riociguat-Former Placebo | Number of Participants With Death | 13 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.
Time frame: From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 96 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related serious TEAE | 14 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related TEAE | 77 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAT leading to death | 22 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 153 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAT leading to death | 13 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 82 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related TEAE | 44 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related serious TEAE | 7 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 56 Participants |
Secondary
Change From Baseline of Hemoglobin in Hematology and Coagulation
Hemoglobin is standard Hematology and coagulation parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline of Hemoglobin in Hematology and Coagulation | Baseline (Week 0) | 14.49 gram/deciliter (g/dL) | Standard Deviation 1.82 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline of Hemoglobin in Hematology and Coagulation | Change from baseline to Termination visit | 1.04 gram/deciliter (g/dL) | Standard Deviation 1.58 |
| Riociguat-Former Placebo | Change From Baseline of Hemoglobin in Hematology and Coagulation | Baseline (Week 0) | 14.36 gram/deciliter (g/dL) | Standard Deviation 1.7 |
| Riociguat-Former Placebo | Change From Baseline of Hemoglobin in Hematology and Coagulation | Change from baseline to Termination visit | -1.37 gram/deciliter (g/dL) | Standard Deviation 1.71 |
Secondary
Change From Baseline of Urate in Clinical Chemistry
Urate is standard clinical chemistry parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline of Urate in Clinical Chemistry | Baseline (Week 0) | 6.767 milligram/deciliter (mg/dL) | Standard Deviation 1.859 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline of Urate in Clinical Chemistry | Change from baseline to Termination visit | 0.310 milligram/deciliter (mg/dL) | Standard Deviation 2.916 |
| Riociguat-Former Placebo | Change From Baseline of Urate in Clinical Chemistry | Baseline (Week 0) | 6.999 milligram/deciliter (mg/dL) | Standard Deviation 2.193 |
| Riociguat-Former Placebo | Change From Baseline of Urate in Clinical Chemistry | Change from baseline to Termination visit | -1.290 milligram/deciliter (mg/dL) | Standard Deviation 1.12 |
Secondary
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit, and for each parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alanine aminotransferase (U/L) | 11.5 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alkaline phosphatase (U/L) | 22.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Aspartate aminotransferase (U/L) | 16.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 17.2 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 2.6 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatine kinase (U/L) | 28.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 32.5 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Gamma glutamyltransferase (U/L) | 22.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Glutamate dehydrogenase (U/L) | 43.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 7.9 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 4.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 2.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 2.1 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 1.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol lipase (U/L) | 18.8 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 13.6 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 22.9 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | eGFR MDRD method(mL/min/1.73 m2) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine clearance (mL/min) | 11.5 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 36.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alanine aminotransferase (U/L) | 13.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 5.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol lipase (U/L) | 18.8 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alkaline phosphatase (U/L) | 19.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 6.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Aspartate aminotransferase (U/L) | 14.1 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine clearance (mL/min) | 8.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 15.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 35.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatine kinase (U/L) | 30.3 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 31.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | eGFR MDRD method(mL/min/1.73 m2) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Gamma glutamyltransferase (U/L) | 24.1 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 3.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Glutamate dehydrogenase (U/L) | 34.0 Percentage |
Secondary
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit, and for each parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils (Giga/L) | 1.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils (Giga/L) | 0.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes / Leukocytes (%) | 8.8 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 18.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 3.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils / Leukocytes (%) | 18.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes / Leukocytes (%) | 15.6 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 41.2 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 11.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils / Leukocytes (%) | 3.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils / Leukocytes (%) | 31.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 12.5 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 17.2 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 8.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Prothrombin international normalized ratio | 92.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Activated partial thromboplastin time (sec) | 97.1 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Prothrombin international normalized ratio | 75 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Activated partial thromboplastin time (sec) | 90.5 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils (Giga/L) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils / Leukocytes (%) | 16.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils (Giga/L) | 5.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 10.8 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils / Leukocytes (%) | 9.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 24.2 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 38.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 16.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 1.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes / Leukocytes (%) | 7.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 8.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes / Leukocytes (%) | 16.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 23.3 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils / Leukocytes (%) | 32.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 20.6 Percentage |
Secondary
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit, and for each parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 2.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alkaline phosphatase (U/L) | 2.1 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 14.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatine kinase (U/L) | 6.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 4.1 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Gamma glutamyltransferase (U/L) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 10.5 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 18.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 6.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 10.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 4.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol lipase (U/L) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 2.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | eGFR MDRDmethod (mL/min/1.73 m2) | 26.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine clearance (mL/min) | 29.2 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol lipase (U/L) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine clearance (mL/min) | 40.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alkaline phosphatase (U/L) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 2.8 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 2.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 18.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 6.3 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 14.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatine kinase (U/L) | 6.8 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | eGFR MDRDmethod (mL/min/1.73 m2) | 22.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 3.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 6.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Gamma glutamyltransferase (U/L) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 1.3 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 9.5 Percentage |
Secondary
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit, and for each parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 9.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 0.7 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 25.4 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes / Leukocytes (%) | 3.6 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 21.1 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 10.8 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 30.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils / Leukocytes (%) | 5.8 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 30.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 19.8 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes / Leukocytes (%) | 39.3 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 0.0 Percentage |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Activated partial thromboplastin time (sec) | 2.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Activated partial thromboplastin time (sec) | 2.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 29.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 17.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 36.2 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 25.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 22.4 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes / Leukocytes (%) | 42.9 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 0.0 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes / Leukocytes (%) | 2.7 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 5.6 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils / Leukocytes (%) | 10.1 Percentage |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 19.4 Percentage |
Other Pre-specified
Change From Baseline in Borg CR 10 Scale
The Borg CR10 Scale was measured in conjunction with the 6MWD test. The test was explained to the participant before starting the 6MWD test. Participants were asked to rank their exertion at the end of the 6MWD 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: From baseline to Week 12
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline in Borg CR 10 Scale | Baseline (Week 0) | 4.36 Scores on a scale | Standard Deviation 2.3 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline in Borg CR 10 Scale | Change from baseline to Week 12 | -0.93 Scores on a scale | Standard Deviation 2.47 |
| Riociguat-Former Placebo | Change From Baseline in Borg CR 10 Scale | Baseline (Week 0) | 4.45 Scores on a scale | Standard Deviation 2.26 |
| Riociguat-Former Placebo | Change From Baseline in Borg CR 10 Scale | Change from baseline to Week 12 | -0.3 Scores on a scale | Standard Deviation 2.08 |
Other Pre-specified
Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
NT-proBNP levels in the blood are used for diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure
Time frame: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Baseline (Week 0) | 1553.19 picograms/millilitre (pg/mL) | Standard Deviation 2435.94 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Change from baseline to End of study visit | -125.99 picograms/millilitre (pg/mL) | Standard Deviation 2503.78 |
| Riociguat-Former Placebo | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Baseline (Week 0) | 1404.23 picograms/millilitre (pg/mL) | Standard Deviation 1745.48 |
| Riociguat-Former Placebo | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Change from baseline to End of study visit | -187.96 picograms/millilitre (pg/mL) | Standard Deviation 1438.96 |
Other Pre-specified
Change in Pulmonary Vascular Resistance (PVR)
Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. Analyses up to Month 48 due to limited data.
Time frame: From baseline to Month 45 and Month 48
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Pulmonary Vascular Resistance (PVR) | Baseline (Week 0) | 796.64 dyn*s*cm^-5 | Standard Deviation 435.24 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Pulmonary Vascular Resistance (PVR) | Change from baseline to Month 48 | -148.29 dyn*s*cm^-5 | Standard Deviation 74.39 |
| Riociguat-Former Placebo | Change in Pulmonary Vascular Resistance (PVR) | Baseline (Week 0) | 761.83 dyn*s*cm^-5 | Standard Deviation 388.87 |
| Riociguat-Former Placebo | Change in Pulmonary Vascular Resistance (PVR) | Change from baseline to Month 45 | -1243.48 dyn*s*cm^-5 | — |
Other Pre-specified
Change in Score of EQ-5D Questionnaire
The EQ-5D is a standardized instrument for use as a measure of health outcome. The EQ-5D is a self report questionnaire. 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: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of EQ-5D Questionnaire | Baseline (Week 0) | 0.6406 Scores on a scale | Standard Deviation 0.2509 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of EQ-5D Questionnaire | Change from baseline to EOS Visit | -0.1008 Scores on a scale | Standard Deviation 0.4965 |
| Riociguat-Former Placebo | Change in Score of EQ-5D Questionnaire | Baseline (Week 0) | 0.6569 Scores on a scale | Standard Deviation 0.2518 |
| Riociguat-Former Placebo | Change in Score of EQ-5D Questionnaire | Change from baseline to EOS Visit | -0.1230 Scores on a scale | Standard Deviation 0.5213 |
Other Pre-specified
Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire
The LPH questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH is a self-report questionnaire and was completed by the participant. The LPH total score can range from 0 (best) to 105 (worst).
Time frame: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Baseline (Week 0) | 42.19 Scores on a scale | Standard Deviation 22.05 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Change from baseline to EOS Visit | -2.64 Scores on a scale | Standard Deviation 29.26 |
| Riociguat-Former Placebo | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Change from baseline to EOS Visit | -0.56 Scores on a scale | Standard Deviation 30.83 |
| Riociguat-Former Placebo | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Baseline (Week 0) | 46.01 Scores on a scale | Standard Deviation 22.93 |
Other Pre-specified
Change in Six-minute Walking Distance (6MWD) Test
6MWD is exercise testing and is one of efficacy evaluation
Time frame: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Baseline (Week 0) | 361.0 meters |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Change from baseline to End of study visit | 31.0 meters |
| Riociguat-Former Placebo | Change in Six-minute Walking Distance (6MWD) Test | Baseline (Week 0) | 372.0 meters |
| Riociguat-Former Placebo | Change in Six-minute Walking Distance (6MWD) Test | Change from baseline to End of study visit | 12.5 meters |
Other Pre-specified
Change in World Health Organization (WHO) Functional Class
WHO classification: I: Participants with PH. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Participants with PH are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Participants with PH are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Participants with PH with inability to carry out any physical activity. They manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. For class change from baseline, minus indicates a participant's functional class decreased compared with baseline (e.g. -1 indicates a participant changed from class IV to class III, or from class II to class I), plus indicates a participant's functional class increased compared with baseline (e.g. +1 indicates a participant changed from class I to class II, or from class III to class IV).
Time frame: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class I | 3 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class II | 48 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class III | 100 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class IV | 4 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-Missing | 0 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -2 | 7 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -1 | 44 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -0 | 72 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +1 | 11 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +2 | 13 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +3 | 7 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +4 | 1 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +3 | 6 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class I | 0 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -1 | 24 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class II | 25 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +2 | 7 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class III | 54 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -0 | 38 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class IV | 2 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +4 | 0 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-Missing | 1 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- +1 | 2 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to End of study visit- -2 | 4 Participants |
Other Pre-specified
Change of Arterial Partial Oxygen Pressure (PaO2)
PaO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Oxygen Pressure (PaO2) | Baseline (Week 0) | 69.66 mmHg | Standard Deviation 11.9 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Oxygen Pressure (PaO2) | From baseline to Termination visit | -1.67 mmHg | Standard Deviation 8.02 |
| Riociguat-Former Placebo | Change of Arterial Partial Oxygen Pressure (PaO2) | Baseline (Week 0) | 69.19 mmHg | Standard Deviation 10.96 |
| Riociguat-Former Placebo | Change of Arterial Partial Oxygen Pressure (PaO2) | From baseline to Termination visit | 2.00 mmHg | Standard Deviation 24.73 |
Other Pre-specified
Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
PaCO2 is one parameter of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Baseline (Week 0) | 33.20 mmHg | Standard Deviation 4.61 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | From baseline to Termination visit | -0.33 mmHg | Standard Deviation 1.53 |
| Riociguat-Former Placebo | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Baseline (Week 0) | 33.52 mmHg | Standard Deviation 4.6 |
| Riociguat-Former Placebo | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | From baseline to Termination visit | -2.25 mmHg | Standard Deviation 4.5 |
Other Pre-specified
Change of Diastolic Blood Pressure (DBP)
DBP was measured after the participants had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Diastolic Blood Pressure (DBP) | Baseline (Week 0) | 75.34 mmHg | Standard Deviation 9.75 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Diastolic Blood Pressure (DBP) | Change from baseline to Termination visit | -6.16 mmHg | Standard Deviation 13.77 |
| Riociguat-Former Placebo | Change of Diastolic Blood Pressure (DBP) | Baseline (Week 0) | 78.55 mmHg | Standard Deviation 9.46 |
| Riociguat-Former Placebo | Change of Diastolic Blood Pressure (DBP) | Change from baseline to Termination visit | -7.26 mmHg | Standard Deviation 11.09 |
Other Pre-specified
Change of Heart Rate
Heart rate was measured after the participant had been at rest for 10 minutes in a supine position. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Heart Rate | Baseline (Week 0) | 77.66 beats/minute (BPM) | Standard Deviation 12.12 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Heart Rate | Change from baseline to Termination visit | -0.89 beats/minute (BPM) | Standard Deviation 13.85 |
| Riociguat-Former Placebo | Change of Heart Rate | Baseline (Week 0) | 76.11 beats/minute (BPM) | Standard Deviation 12.1 |
| Riociguat-Former Placebo | Change of Heart Rate | Change from baseline to Termination visit | 3.77 beats/minute (BPM) | Standard Deviation 14.69 |
Other Pre-specified
Change of Oxygen Saturation (SaO2)
SaO2 is one parameters of blood gas. The sample was obtained with the participant resting in a sitting or supine position for at least 10 minutes. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Oxygen Saturation (SaO2) | Baseline (Week 0) | 93.9 Percentage | Standard Deviation 2.7 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Oxygen Saturation (SaO2) | From baseline to Termination visit | 0.0 Percentage | Standard Deviation 2.6 |
| Riociguat-Former Placebo | Change of Oxygen Saturation (SaO2) | Baseline (Week 0) | 93.6 Percentage | Standard Deviation 2.4 |
| Riociguat-Former Placebo | Change of Oxygen Saturation (SaO2) | From baseline to Termination visit | -2.3 Percentage | Standard Deviation 5.5 |
Other Pre-specified
Change of PR Duration From ECG
PR duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.
Time frame: From baseline to Month 48
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of PR Duration From ECG | Baseline (Week 0) | 173.22 msec | Standard Deviation 26.49 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of PR Duration From ECG | Change from baseline to Month 48 | -10.00 msec | Standard Deviation 11.31 |
| Riociguat-Former Placebo | Change of PR Duration From ECG | Baseline (Week 0) | 174.92 msec | Standard Deviation 24.35 |
Other Pre-specified
Change of QRS Duration From ECG
QRS duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.
Time frame: From baseline to Month 48
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QRS Duration From ECG | Baseline (Week 0) | 104.30 msec | Standard Deviation 17.85 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QRS Duration From ECG | Change from baseline to Month 48 | 3.00 msec | Standard Deviation 4.24 |
| Riociguat-Former Placebo | Change of QRS Duration From ECG | Baseline (Week 0) | 104.11 msec | Standard Deviation 18.24 |
Other Pre-specified
Change of QT Duration in ECG
QT duration was evaluated as part of ECG. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.
Time frame: From baseline to Month 48
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QT Duration in ECG | Baseline (Week 0) | 405.82 msec | Standard Deviation 31.29 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QT Duration in ECG | Change from baseline to Month 48 | 42.00 msec | Standard Deviation 39.6 |
| Riociguat-Former Placebo | Change of QT Duration in ECG | Baseline (Week 0) | 408.45 msec | Standard Deviation 30.98 |
Other Pre-specified
Change of RR Duration From Electrocardiogram (ECG)
Heart rate from ECG is derived from the RR duration, unless arrhythmias such as atrial fibrillation or ventricular extra beats require additional calculations. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. Analyses up to Month 48. After this timepoint, data was available for considerably fewer participants in the analysis set.
Time frame: From baseline to Month 48
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of RR Duration From Electrocardiogram (ECG) | Baseline (Week 0) | 812.90 millisecond (msec) | Standard Deviation 144.31 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of RR Duration From Electrocardiogram (ECG) | Change rom baseline to Month 48 | 152.00 millisecond (msec) | Standard Deviation 236.17 |
| Riociguat-Former Placebo | Change of RR Duration From Electrocardiogram (ECG) | Baseline (Week 0) | 828.47 millisecond (msec) | Standard Deviation 147.54 |
Other Pre-specified
Change of Systolic Blood Pressure (SBP)
SBP was measured after the participant had been at rest for 10 minutes in a supine position. Low SBP was defined as SBP \<95 mmHg, normal SBP as SBP 95-140mmHg, and high SBP as SBP \>140 mmHg. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Systolic Blood Pressure (SBP) | Baseline (Week 0) | 118.81 millimetre(s) of mercury (mmHg) | Standard Deviation 14.96 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Systolic Blood Pressure (SBP) | Change from baseline to Termination visit | -3.96 millimetre(s) of mercury (mmHg) | Standard Deviation 17.34 |
| Riociguat-Former Placebo | Change of Systolic Blood Pressure (SBP) | Baseline (Week 0) | 124.26 millimetre(s) of mercury (mmHg) | Standard Deviation 16.14 |
| Riociguat-Former Placebo | Change of Systolic Blood Pressure (SBP) | Change from baseline to Termination visit | -5.02 millimetre(s) of mercury (mmHg) | Standard Deviation 14.79 |
Other Pre-specified
Change of Weight
Weight was evaluated for safety. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Time frame: From baseline to Termination visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Weight | Baseline (Week 0) | 74.01 kilogram (kg) | Standard Deviation 18.76 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Weight | From baseline to Termination visit | -0.87 kilogram (kg) | Standard Deviation 5.86 |
| Riociguat-Former Placebo | Change of Weight | Baseline (Week 0) | 77.29 kilogram (kg) | Standard Deviation 16.42 |
| Riociguat-Former Placebo | Change of Weight | From baseline to Termination visit | -2.97 kilogram (kg) | Standard Deviation 7.27 |
Other Pre-specified
Incidence of Clinical Worsening Events Per 100 Person Years
Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH).
Time frame: From baseline to End of study visit, up to 10 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Death | 4.04 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Any clinical worsening event | 12.84 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Pulmonary endarterectomy | 0.73 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Hospitalization due to PH | 1.65 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Start of new PH treatment | 4.40 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Decrease in 6MWD due to PH | 0.73 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Persistent worsening of functional class due to PH | 1.28 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Death | 4.50 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Start of new PH treatment | 3.81 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Any clinical worsening event | 11.77 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Persistent worsening of functional class due to PH | 0.69 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Pulmonary endarterectomy | 1.04 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Decrease in 6MWD due to PH | 0.69 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Hospitalization due to PH | 1.04 Percentage per 100 person-years |
Other Pre-specified
Number of Participants With Clinical Worsening
Time to clinical worsening was a parameter that combined death and events reflective of persistent clinical worsening of the participant's underlying diagnosis of pulmonary hypertension (PH).
Time frame: From baseline to End of study visit, up to 10 years
Population: Participants in SAF with evaluable data for each visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Hospitalization due to PH | 7 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Decrease in 6MWD due to PH | 4 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Pulmonary endarterectomy | 4 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Persistent worsening of functional class due to PH | 7 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Start of new PH treatment | 21 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Death | 22 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Any clinical worsening | 45 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Death | 13 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Any clinical worsening | 23 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Pulmonary endarterectomy | 3 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Hospitalization due to PH | 3 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Start of new PH treatment | 9 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Decrease in 6MWD due to PH | 2 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Persistent worsening of functional class due to PH | 2 Participants |