Hypertension, Pulmonary
Conditions
Keywords
Pulmonary arterial hypertension, PH, Stimulator
Brief summary
Patients who have completed the 12 weeks treatment of the PATENT-1 trial (study number 12934) will be asked to participate in this long term extension study with BAY63-2521.
Interventions
BAY63-2521: 1mg tid -2.5 mg tid oral 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 12 weeks of treatment in the double blind trial PATENT 1
Exclusion criteria
* Patients who have an ongoing serious adverse event from PATENT 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 Participant With Death | From baseline to end of safety follow-up visit, up to 10 years and 6 months (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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | From administration of first dose of study medication in PATENT-2 up to 2 days after end of treatment with study medication, up to 10 years and 5 months. | Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication. |
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 | Percentage 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. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after 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 | Percentage 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. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after 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 High Laboratory Abnormalities in Clinical Chemistry | From baseline to termination visit, up to 10 years | Percentage 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. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after 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 | Percentage 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. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 and 5 months. | 6MWD is exercise testing and is one of efficacy evaluation |
| Change in Pulmonary Vascular Resistance (PVR) | From baseline to Termination visit, up to 10 years 5 months | Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. 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 in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | From baseline to End of study visit, up to 10 year and 5 months | 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 in World Health Organization (WHO) Functional Class | From baseline to End of study visit, up to 10 years and 5 months. | 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). |
| Number of Participants With Clinical Worsening | From baseline to End of study visit, up to 10 years and 5 months. | 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 and 5 months. | 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 and 5 months. | 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 and 5 months. | 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 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. |
| 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 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Mexico, Poland, Portugal, Russia, Singapore, South Korea, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at 97 centers in 27 countries between 12-MAR-2009 (first participant first visit) and 19-AUG-2019 (last participant last visit);
Pre-assignment details
Of the 405 participants who completed PATENT-1(NCT00810693) study, 396 participants entered PATENT-2 study. 231 participants were from the former riociguat 1.0-2.5mg group, 109 were from the former placebo group and 56 were from the former riociguat 1.0-1.5mg group.
Participants by arm
| Arm | Count |
|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 2.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1. | 231 |
| Riociguat-Former Placebo Participants were from the former placebo group of PATENT-1. The starting dose in PATENT-2 was 1.0 mg riociguat three times one day. | 109 |
| Riociguat-Former Riociguat 1.0-1.5 mg Participants from the former riociguat (BAY 63-2521) 1.0 - 1.5 mg treatment group in PATENT-1 on the same dose as they received on the last day of PATENT-1. | 56 |
| Total | 396 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 28 | 10 | 6 |
| Overall Study | Death | 40 | 23 | 6 |
| Overall Study | Lack of Efficacy | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 | 3 |
| Overall Study | Missing | 1 | 0 | 0 |
| Overall Study | Non-compliance with study drug | 1 | 3 | 0 |
| Overall Study | Other | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 5 | 2 |
Baseline characteristics
| Characteristic | Riociguat-Former Riociguat 1.0-1.5 mg | Total | Riociguat-Former Riociguat 1.0-2.5 mg | Riociguat-Former Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 90 Participants | 57 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 306 Participants | 174 Participants | 87 Participants |
| Age, Continuous | 48.2 years STANDARD_DEVIATION 16.3 | 49.7 years STANDARD_DEVIATION 16.2 | 50.4 years STANDARD_DEVIATION 16.4 | 48.8 years STANDARD_DEVIATION 15.9 |
| Race/Ethnicity, Customized Asian | 20 Participants | 127 Participants | 74 Participants | 33 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants | 22 Participants | 7 Participants | 8 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 242 Participants | 148 Participants | 66 Participants |
| Sex: Female, Male Female | 44 Participants | 317 Participants | 186 Participants | 87 Participants |
| Sex: Female, Male Male | 12 Participants | 79 Participants | 45 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 48 / 231 | 7 / 56 | 30 / 109 |
| other Total, other adverse events | 218 / 231 | 54 / 56 | 106 / 109 |
| serious Total, serious adverse events | 161 / 231 | 39 / 56 | 76 / 109 |
Outcome results
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 in PATENT-2 up to 2 days after end of treatment with study medication, up to 10 years and 5 months.
| 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 drug-related serious TEAE | 25 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 161 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 229 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related TEAE | 138 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE leading to death | 42 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 108 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related TEAE | 74 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 76 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related serious TEAE | 16 Participants |
| Riociguat-Former Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE leading to death | 25 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE leading to death | 6 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related serious TEAE | 3 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any TEAE | 56 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any serious TEAE | 39 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Any drug-related TEAE | 30 Participants |
Primary
Number of Participant 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 and 6 months (1 month more than End of study visit)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participant With Death | 48 Participants |
| Riociguat-Former Placebo | Number of Participant With Death | 30 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participant With Death | 7 Participants |
Secondary
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Percentage 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. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after 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 | Pseudocholinesterase (U/mL) | 0.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 29.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 20.1 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 2.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase(U/L) | 18.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 4.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Glutamate Dehydrogenase (U/L) | 40.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 12.1 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 2.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 24.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 15.7 Percentage of participants |
| 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 m*2) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol Lipase (U/L) | 22.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Aspartate Aminotransferase (U/L) | 11.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Calcium(mg/dL) | 2.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 13.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 0.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 23.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 14.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 18.9 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 11.8 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 12.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 1.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 23.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Calcium(mg/dL) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 24.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 39.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase(U/L) | 17.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Glutamate Dehydrogenase (U/L) | 37.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 4.9 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 4.9 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 1.9 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol Lipase (U/L) | 19.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 25.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Aspartate Aminotransferase (U/L) | 11.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | eGFR - MDRD Method (mL/min/1.73 m*2) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 15.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 30.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Calcium(mg/dL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 28.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 3.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 15.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 13.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol Lipase (U/L) | 12.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | eGFR - MDRD Method (mL/min/1.73 m*2) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Glutamate Dehydrogenase (U/L) | 56.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 29.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase(U/L) | 25.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 8.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 8.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 45.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Aspartate Aminotransferase (U/L) | 10.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 3.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 19.1 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Percentage 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. The percentage was calculated by comparing the number of participants with a normal or low value at baseline who had at least one high value after the start of treatment with the number of participants with a normal or low value at baseline who also had at least one valid value after 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 | Monocytes (Giga/L) | 6.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 35.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils (Giga/L) | 1.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 68.1 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 8.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 42.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 11.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 10.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils (Giga/L) | 1.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 1.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 56.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 14.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils/Leukocytes (%) | 8.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 14.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 20.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 13.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils/Leukocytes (%) | 16.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 19.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 80.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils (Giga/L) | 1.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils/Leukocytes (%) | 12.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils (Giga/L) | 2.2 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils/Leukocytes (%) | 3.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 21.8 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 37.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 16.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 13.6 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 3.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 3.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 18.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 18.8 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 38.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 9.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 74.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils (Giga/L) | 2.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils/Leukocytes (%) | 10.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 58.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 22.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Eosinophils (Giga/L) | 2.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 15.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 28.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Basophils/Leukocytes (%) | 10.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 79.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 22.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 52.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 24.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 48.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 6.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 35.0 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Percentage 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. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after 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 | Pseudocholinesterase (U/mL) | 11.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 5.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 24.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 9.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 8.5 Percentage of participants |
| 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 of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 3.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 0.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | eGFR - MDRD Method(mL/min/1.73 m*2) | 19.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 45.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 8.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 4.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 4.1 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 3.3 Percentage of participants |
| 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 of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 25.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 10.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | eGFR - MDRD Method(mL/min/1.73 m*2) | 17.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 6.9 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 15.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 4.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 4.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 32.6 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 30.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 1.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 10.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 1.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 11.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 5.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 5.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 13.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol Lipase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Sodium (mmol/L) | 11.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Triacylglycerol Lipase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urate (mg/dL) | 3.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Albumin (g/dL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Urea (mg/dL) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Calcium (mg/dL) | 20.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | eGFR - MDRD Method(mL/min/1.73 m*2) | 23.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine Clearance (mL/min) | 48.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alkaline Phosphatase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatine Kinase (U/L) | 12.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Gamma Glutamyl Transferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Phosphate (mg/dL) | 33.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Creatinine (mg/dL) | 5.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Potassium (mmol/L) | 29.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Protein (g/dL) | 8.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Pseudocholinesterase (U/mL) | 8.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Alanine Aminotransferase (U/L) | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry | Bilirubin (mg/dL) | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Percentage 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. The percentage was calculated by comparing the number of participants with a normal or high value at baseline who had at least one low value after the start of treatment with the number of participants with a normal or high value at baseline who also had at least one valid value after 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 | Platelets (Giga/L) | 23.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 2.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 29.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 22.1 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 0.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 50.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 12.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 31.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 6.9 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 48.2 Percentage of participants |
| 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 of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 9.4 Percentage of participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 25.7 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 44.6 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 13.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 22.8 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 23.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 38.0 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 23.6 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 29.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 1.1 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 3.3 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 4.4 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 4.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 29.5 Percentage of participants |
| Riociguat-Former Placebo | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 0.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes/Leukocytes (%) | 14.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hemoglobin (g/dL) | 46.2 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Platelets (Giga/L) | 26.8 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils (Giga/L) | 8.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Hematocrit (%) | 26.7 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | aPTT (Sec) | 8.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Neutrophils/Leukocytes (%) | 6.5 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes/Leukocytes (%) | 64.3 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Lymphocytes (Giga/L) | 32.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Erythrocytes (T/L) | 25.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Monocytes (Giga/L) | 2.0 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Leukocytes (Giga/L) | 25.6 Percentage of participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation | Prothrombin INR | 0.0 Percentage of participants |
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) | 3.87 Scores on a scale | Standard Deviation 2.24 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change From Baseline in Borg CR 10 Scale | Change from baseline to Week 12 | -0.58 Scores on a scale | Standard Deviation 1.84 |
| Riociguat-Former Placebo | Change From Baseline in Borg CR 10 Scale | Baseline (Week 0) | 3.80 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 | -0.54 Scores on a scale | Standard Deviation 1.91 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change From Baseline in Borg CR 10 Scale | Baseline (Week 0) | 3.41 Scores on a scale | Standard Deviation 1.77 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change From Baseline in Borg CR 10 Scale | Change from baseline to Week 12 | -0.52 Scores on a scale | Standard Deviation 1.64 |
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 year and 5 months
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) | 996.30 picograms/millilitre (pg/mL) | Standard Deviation 1627.48 |
| 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 | 82.52 picograms/millilitre (pg/mL) | Standard Deviation 2253.3 |
| Riociguat-Former Placebo | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Baseline (Week 0) | 1135.68 picograms/millilitre (pg/mL) | Standard Deviation 1533.2 |
| Riociguat-Former Placebo | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Change from baseline to End of study visit | 202.42 picograms/millilitre (pg/mL) | Standard Deviation 3466.94 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Baseline (Week 0) | 1220.11 picograms/millilitre (pg/mL) | Standard Deviation 1457.9 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Change from baseline to End of study visit | 115.77 picograms/millilitre (pg/mL) | Standard Deviation 1918.81 |
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. 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 5 months
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) | 802.40 dyn*s*cm^-5 | Standard Deviation 452.97 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Pulmonary Vascular Resistance (PVR) | Change from baseline to Termination visit | 34.25 dyn*s*cm^-5 | Standard Deviation 104.83 |
| Riociguat-Former Placebo | Change in Pulmonary Vascular Resistance (PVR) | Baseline (Week 0) | 835.45 dyn*s*cm^-5 | Standard Deviation 476.52 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Pulmonary Vascular Resistance (PVR) | Baseline (Week 0) | 855.70 dyn*s*cm^-5 | Standard Deviation 552.92 |
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 and 5 months.
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) | 0.6883 Scores on a scale | Standard Deviation 0.2339 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of EQ-5D Questionnaire | Change from baseline to EOS Visit | -0.2452 Scores on a scale | Standard Deviation 0.5894 |
| Riociguat-Former Placebo | Change in Score of EQ-5D Questionnaire | Baseline (Week 0) | 0.6929 Scores on a scale | Standard Deviation 0.2302 |
| Riociguat-Former Placebo | Change in Score of EQ-5D Questionnaire | Change from baseline to EOS Visit | -0.2812 Scores on a scale | Standard Deviation 0.5944 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Score of EQ-5D Questionnaire | Baseline (Week 0) | 0.6338 Scores on a scale | Standard Deviation 0.2744 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Score of EQ-5D Questionnaire | Change from baseline to EOS Visit | -0.0925 Scores on a scale | Standard Deviation 0.4376 |
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 and 5 months.
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) | 41.77 Scores on a scale | Standard Deviation 22.18 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Change from baseline to EOS Visit | 4.99 Scores on a scale | Standard Deviation 34.04 |
| Riociguat-Former Placebo | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Baseline (Week 0) | 41.94 Scores on a scale | Standard Deviation 23.34 |
| Riociguat-Former Placebo | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Change from baseline to EOS Visit | 12.28 Scores on a scale | Standard Deviation 32.76 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Baseline (Week 0) | 45.10 Scores on a scale | Standard Deviation 22.08 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire | Change from baseline to EOS Visit | -4.07 Scores on a scale | Standard Deviation 31.4 |
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 and 5 months.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Baseline (Week 0) | 375.0 meters | Full Range 160 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Change from baseline to End of study visit | 19.0 meters | Full Range -448 |
| Riociguat-Former Placebo | Change in Six-minute Walking Distance (6MWD) Test | Baseline (Week 0) | 395.0 meters | Full Range 174 |
| Riociguat-Former Placebo | Change in Six-minute Walking Distance (6MWD) Test | Change from baseline to End of study visit | 9.0 meters | Full Range -446 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Baseline (Week 0) | 376.0 meters | Full Range 158 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in Six-minute Walking Distance (6MWD) Test | Change from baseline to End of study visit | 1.5 meters | Full Range -448 |
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 and 5 months.
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 | Change from baseline to EOS visit- 0 | 101 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 EOS visit- +2 | 33 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -1 | 50 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -2 | 5 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class I | 5 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class III | 128 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class II | 98 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +1 | 23 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class IV | 0 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +3 | 19 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -2 | 0 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class I | 3 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class II | 54 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class III | 49 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 | Baseline (Week 0)-Missing | 1 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -1 | 16 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- 0 | 52 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +1 | 15 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +2 | 17 Participants |
| Riociguat-Former Placebo | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +3 | 8 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +2 | 5 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- 0 | 28 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class III | 35 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class I | 4 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +1 | 6 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class II | 17 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -2 | 1 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-Missing | 0 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- +3 | 3 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Change from baseline to EOS visit- -1 | 13 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change in World Health Organization (WHO) Functional Class | Baseline (Week 0)-class IV | 0 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) | 76.99 mmHg | Standard Deviation 17.6 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Oxygen Pressure (PaO2) | Change from baseline to Termination visit | -4.77 mmHg | Standard Deviation 17.42 |
| Riociguat-Former Placebo | Change of Arterial Partial Oxygen Pressure (PaO2) | Baseline (Week 0) | 74.54 mmHg | Standard Deviation 17.84 |
| Riociguat-Former Placebo | Change of Arterial Partial Oxygen Pressure (PaO2) | Change from baseline to Termination visit | 7.14 mmHg | Standard Deviation 58 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Arterial Partial Oxygen Pressure (PaO2) | Baseline (Week 0) | 72.12 mmHg | Standard Deviation 13.63 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Arterial Partial Oxygen Pressure (PaO2) | Change from baseline to Termination visit | -8.05 mmHg | Standard Deviation 2.76 |
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) | 32.94 mmHg | Standard Deviation 4.62 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Change from baseline to Termination visit | -1.87 mmHg | Standard Deviation 3.72 |
| Riociguat-Former Placebo | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Baseline (Week 0) | 32.46 mmHg | Standard Deviation 4.63 |
| Riociguat-Former Placebo | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Change from baseline to Termination visit | -0.68 mmHg | Standard Deviation 5.7 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Baseline (Week 0) | 33.40 mmHg | Standard Deviation 4.41 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Change from baseline to Termination visit | 2.00 mmHg | Standard Deviation 4.24 |
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) | 72.03 mmHg | Standard Deviation 10.53 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Diastolic Blood Pressure (DBP) | Change from baseline to Termination visit | -3.33 mmHg | Standard Deviation 12.9 |
| Riociguat-Former Placebo | Change of Diastolic Blood Pressure (DBP) | Baseline (Week 0) | 71.84 mmHg | Standard Deviation 9.06 |
| Riociguat-Former Placebo | Change of Diastolic Blood Pressure (DBP) | Change from baseline to Termination visit | -4.00 mmHg | Standard Deviation 11.72 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Diastolic Blood Pressure (DBP) | Baseline (Week 0) | 69.61 mmHg | Standard Deviation 9.89 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Diastolic Blood Pressure (DBP) | Change from baseline to Termination visit | -2.13 mmHg | Standard Deviation 9.65 |
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) | 76.47 beats/minute (BPM) | Standard Deviation 11.04 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Heart Rate | Change from baseline to Termination visit | 0.75 beats/minute (BPM) | Standard Deviation 13.92 |
| Riociguat-Former Placebo | Change of Heart Rate | Baseline (Week 0) | 77.30 beats/minute (BPM) | Standard Deviation 12.53 |
| Riociguat-Former Placebo | Change of Heart Rate | Change from baseline to Termination visit | 0.18 beats/minute (BPM) | Standard Deviation 14.07 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Heart Rate | Baseline (Week 0) | 76.04 beats/minute (BPM) | Standard Deviation 10.83 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Heart Rate | Change from baseline to Termination visit | -1.10 beats/minute (BPM) | Standard Deviation 14.74 |
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) | 95.10 Percentage | Standard Deviation 2.61 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Oxygen Saturation (SaO2) | Change from baseline to Termination visit | -1.14 Percentage | Standard Deviation 3.48 |
| Riociguat-Former Placebo | Change of Oxygen Saturation (SaO2) | Baseline (Week 0) | 94.32 Percentage | Standard Deviation 3.18 |
| Riociguat-Former Placebo | Change of Oxygen Saturation (SaO2) | Change from baseline to Termination visit | -0.56 Percentage | Standard Deviation 4.45 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Oxygen Saturation (SaO2) | Baseline (Week 0) | 94.00 Percentage | Standard Deviation 2.95 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Oxygen Saturation (SaO2) | Change from baseline to Termination visit | -4.30 Percentage | Standard Deviation 5.23 |
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) | 171.07 msec | Standard Deviation 27.76 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of PR Duration From ECG | Change from baseline to Month 48 | 7.51 msec | Standard Deviation 16.29 |
| Riociguat-Former Placebo | Change of PR Duration From ECG | Baseline (Week 0) | 173.97 msec | Standard Deviation 32.9 |
| Riociguat-Former Placebo | Change of PR Duration From ECG | Change from baseline to Month 48 | 16.50 msec | Standard Deviation 19.41 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of PR Duration From ECG | Baseline (Week 0) | 171.74 msec | Standard Deviation 25.77 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of PR Duration From ECG | Change from baseline to Month 48 | -3.22 msec | Standard Deviation 17.18 |
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) | 99.59 msec | Standard Deviation 17.38 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QRS Duration From ECG | Change from baseline to Month 48 | 5.07 msec | Standard Deviation 8.56 |
| Riociguat-Former Placebo | Change of QRS Duration From ECG | Baseline (Week 0) | 100.09 msec | Standard Deviation 16.15 |
| Riociguat-Former Placebo | Change of QRS Duration From ECG | Change from baseline to Month 48 | 11.14 msec | Standard Deviation 18.69 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of QRS Duration From ECG | Baseline (Week 0) | 103.22 msec | Standard Deviation 19.82 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of QRS Duration From ECG | Change from baseline to Month 48 | -0.44 msec | Standard Deviation 7.52 |
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) | 401.56 msec | Standard Deviation 31.35 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of QT Duration in ECG | Change from baseline to Month 48 | 10.93 msec | Standard Deviation 27.58 |
| Riociguat-Former Placebo | Change of QT Duration in ECG | Baseline (Week 0) | 406.67 msec | Standard Deviation 35.44 |
| Riociguat-Former Placebo | Change of QT Duration in ECG | Change from baseline to Month 48 | 16.89 msec | Standard Deviation 16.78 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of QT Duration in ECG | Baseline (Week 0) | 405.10 msec | Standard Deviation 30.52 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of QT Duration in ECG | Change from baseline to Month 48 | 27.34 msec | Standard Deviation 28.61 |
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) | 817.69 millisecond (msec) | Standard Deviation 125.61 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of RR Duration From Electrocardiogram (ECG) | Change from baseline to Month 48 | 59.07 millisecond (msec) | Standard Deviation 109.89 |
| Riociguat-Former Placebo | Change of RR Duration From Electrocardiogram (ECG) | Baseline (Week 0) | 828.96 millisecond (msec) | Standard Deviation 146.32 |
| Riociguat-Former Placebo | Change of RR Duration From Electrocardiogram (ECG) | Change from baseline to Month 48 | 75.69 millisecond (msec) | Standard Deviation 181.94 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of RR Duration From Electrocardiogram (ECG) | Baseline (Week 0) | 822.33 millisecond (msec) | Standard Deviation 130.27 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of RR Duration From Electrocardiogram (ECG) | Change from baseline to Month 48 | 89.61 millisecond (msec) | Standard Deviation 113.25 |
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) | 114.36 millimetre(s) of mercury (mmHg) | Standard Deviation 14.78 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Systolic Blood Pressure (SBP) | Change from baseline to Termination visit | -0.88 millimetre(s) of mercury (mmHg) | Standard Deviation 15.82 |
| Riociguat-Former Placebo | Change of Systolic Blood Pressure (SBP) | Baseline (Week 0) | 113.75 millimetre(s) of mercury (mmHg) | Standard Deviation 12.76 |
| Riociguat-Former Placebo | Change of Systolic Blood Pressure (SBP) | Change from baseline to Termination visit | -1.30 millimetre(s) of mercury (mmHg) | Standard Deviation 15.62 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Systolic Blood Pressure (SBP) | Baseline (Week 0) | 110.88 millimetre(s) of mercury (mmHg) | Standard Deviation 12.49 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Systolic Blood Pressure (SBP) | Change from baseline to Termination visit | -0.99 millimetre(s) of mercury (mmHg) | Standard Deviation 16.12 |
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 | Change from baseline to Termination visit | -1.67 kilogram (kg) | Standard Deviation 6.45 |
| Riociguat-Former Riociguat 1.0-2.5 mg | Change of Weight | Baseline (Week 0) | 68.24 kilogram (kg) | Standard Deviation 18.25 |
| Riociguat-Former Placebo | Change of Weight | Baseline (Week 0) | 69.03 kilogram (kg) | Standard Deviation 16.94 |
| Riociguat-Former Placebo | Change of Weight | Change from baseline to Termination visit | 0.04 kilogram (kg) | Standard Deviation 6.04 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Weight | Baseline (Week 0) | 69.57 kilogram (kg) | Standard Deviation 14.69 |
| Riociguat-Former Riociguat 1.0-1.5 mg | Change of Weight | Change from baseline to Termination visit | -1.79 kilogram (kg) | Standard Deviation 8.08 |
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 and 5 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Death | 5.49 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 | 4.46 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 | 0.92 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 | 22.09 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 | 9.73 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Atrial Septostomy | 0.11 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-2.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Heart/Lung Transplantation | 0.34 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 | 1.03 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Any clinical worsening event | 22.10 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Heart/Lung Transplantation | 0 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 | 0.51 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Death | 7.62 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Atrial Septostomy | 0.25 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Decrease in 6MWD due to PH | 1.78 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Hospitalization due to PH | 3.81 Percentage per 100 person-years |
| Riociguat-Former Placebo | Incidence of Clinical Worsening Events Per 100 Person Years | Start of new PH treatment | 8.13 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Death | 3.13 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Any clinical worsening event | 19.20 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Atrial Septostomy | 0 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Hospitalization due to PH | 5.80 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Start of new PH treatment | 7.59 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Decrease in 6MWD due to PH | 0.89 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Persistent worsening of functional class due to PH | 0.89 Percentage per 100 person-years |
| Riociguat-Former Riociguat 1.0-1.5 mg | Incidence of Clinical Worsening Events Per 100 Person Years | Heart/Lung Transplantation | 0.89 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 and 5 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Death | 48 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Any clinical worsening | 87 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Heart/lung transplantation | 3 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Atrial septostomy | 1 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 29 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 52 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Decrease in 6MWD due to pulmonary hypertension | 7 Participants |
| Riociguat-Former Riociguat 1.0-2.5 mg | Number of Participants With Clinical Worsening | Persistent worsening of functional class due to PH | 8 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Heart/lung transplantation | 0 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Decrease in 6MWD due to pulmonary hypertension | 6 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Atrial septostomy | 1 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 12 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 20 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Persistent worsening of functional class due to PH | 2 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Any clinical worsening | 41 Participants |
| Riociguat-Former Placebo | Number of Participants With Clinical Worsening | Death | 30 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Heart/lung transplantation | 2 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Decrease in 6MWD due to pulmonary hypertension | 2 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Any clinical worsening | 18 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Atrial septostomy | 0 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Death | 7 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Start of new pulmonary hypertension treatment | 14 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Hospitalization due to pulmonary hypertension | 8 Participants |
| Riociguat-Former Riociguat 1.0-1.5 mg | Number of Participants With Clinical Worsening | Persistent worsening of functional class due to PH | 1 Participants |