Trial Outcomes & Findings for BAY63-2521 - Long-term Extension Study in Patients With Chronic Thromboembolic Pulmonary Hypertension (NCT NCT00910429)
NCT ID: NCT00910429
Last Updated: 2023-11-07
Results Overview
Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
237 participants
Primary outcome timeframe
From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years
Results posted on
2023-11-07
Participant Flow
Study was conducted at 71 centers in 25 countries or regions, between 01-JUL-2009 (first participant first visit) and 19-AUG-2019 (last participant last visit)
Of the 243 participants who completed CHEST-1 (NCT00855465), 237 entered CHEST-2. 155 participants were from the former riociguat treatment group, and 82 were from the former placebo group.
Participant milestones
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Overall Study
STARTED
|
155
|
82
|
|
Overall Study
COMPLETED
|
116
|
61
|
|
Overall Study
NOT COMPLETED
|
39
|
21
|
Reasons for withdrawal
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Overall Study
Death
|
18
|
12
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Adverse Event
|
10
|
5
|
|
Overall Study
Drug non-compliance
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
4
|
1
|
Baseline Characteristics
BAY63-2521 - Long-term Extension Study in Patients With Chronic Thromboembolic Pulmonary Hypertension
Baseline characteristics by cohort
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
Total
n=237 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
91 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
141 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
64 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 13.8 • n=5 Participants
|
59.2 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
59.1 years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
104 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
153 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
105 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
34 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple races
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 yearsAnalyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Any TEAE
|
153 Participants
|
82 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Any drug-related TEAE
|
77 Participants
|
44 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Any serious TEAE
|
96 Participants
|
56 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Any drug-related serious TEAE
|
14 Participants
|
7 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Any TEAT leading to death
|
22 Participants
|
13 Participants
|
PRIMARY outcome
Timeframe: From baseline to end of safety follow-up visit, up to 10 years (1 month more than End of study visit)Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Number of Participants With Death
|
22 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit, and for each parameter.
Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=139 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=74 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Activated partial thromboplastin time (sec)
|
97.1 Percentage
|
90.5 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Basophils (Giga/L)
|
1.4 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Basophils / Leukocytes (%)
|
18.4 Percentage
|
16.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Eosinophils (Giga/L)
|
0.7 Percentage
|
5.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Eosinophils / Leukocytes (%)
|
3.7 Percentage
|
9.7 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Erythrocytes (T/L)
|
18.0 Percentage
|
24.2 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Hematocrit (%)
|
41.2 Percentage
|
38.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Hemoglobin (g/dL)
|
12.5 Percentage
|
10.8 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Leukocytes (Giga/L)
|
8.0 Percentage
|
16.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Lymphocytes (Giga/L)
|
0.0 Percentage
|
1.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Lymphocytes / Leukocytes (%)
|
8.8 Percentage
|
7.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Monocytes (Giga/L)
|
3.7 Percentage
|
8.6 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Monocytes / Leukocytes (%)
|
15.6 Percentage
|
16.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Neutrophils (Giga/L)
|
11.3 Percentage
|
23.3 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Neutrophils / Leukocytes (%)
|
31.7 Percentage
|
32.9 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Platelets (Giga/L)
|
17.2 Percentage
|
20.6 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
Prothrombin international normalized ratio
|
92.3 Percentage
|
75 Percentage
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit, and for each parameter.
Frequency of participants only with a treatment-emergent shift in hematology and coagulation parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=139 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=75 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Activated partial thromboplastin time (sec)
|
2.9 Percentage
|
2.7 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Erythrocytes (T/L)
|
21.1 Percentage
|
29.7 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Hematocrit (%)
|
9.3 Percentage
|
17.6 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Hemoglobin (g/dL)
|
30.0 Percentage
|
36.2 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Leukocytes (Giga/L)
|
25.4 Percentage
|
25.4 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Lymphocytes (Giga/L)
|
30.0 Percentage
|
22.4 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Lymphocytes / Leukocytes (%)
|
39.3 Percentage
|
42.9 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Monocytes (Giga/L)
|
0.7 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Monocytes / Leukocytes (%)
|
3.6 Percentage
|
2.7 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Neutrophils (Giga/L)
|
10.8 Percentage
|
5.6 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Neutrophils / Leukocytes (%)
|
5.8 Percentage
|
10.1 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Platelets (Giga/L)
|
19.8 Percentage
|
19.4 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
Prothrombin INR
|
0.0 Percentage
|
0.0 Percentage
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
Hemoglobin is standard Hematology and coagulation parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=140 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=76 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change From Baseline of Hemoglobin in Hematology and Coagulation
Baseline (Week 0)
|
14.49 gram/deciliter (g/dL)
Standard Deviation 1.82
|
14.36 gram/deciliter (g/dL)
Standard Deviation 1.70
|
|
Change From Baseline of Hemoglobin in Hematology and Coagulation
Change from baseline to Termination visit
|
1.04 gram/deciliter (g/dL)
Standard Deviation 1.58
|
-1.37 gram/deciliter (g/dL)
Standard Deviation 1.71
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit, and for each parameter.
Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or low at baseline to a high value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=147 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=77 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Alanine aminotransferase (U/L)
|
11.5 Percentage
|
13.7 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Albumin (g/dL)
|
0.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Alkaline phosphatase (U/L)
|
22.0 Percentage
|
19.4 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Aspartate aminotransferase (U/L)
|
16.4 Percentage
|
14.1 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Bilirubin (mg/dL)
|
17.2 Percentage
|
15.6 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Calcium (mg/dL)
|
2.6 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Creatine kinase (U/L)
|
28.4 Percentage
|
30.3 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Creatinine (mg/dL)
|
32.5 Percentage
|
31.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Gamma glutamyltransferase (U/L)
|
22.3 Percentage
|
24.1 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Glutamate dehydrogenase (U/L)
|
43.0 Percentage
|
34.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Phosphate (mg/dL)
|
7.9 Percentage
|
5.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Potassium (mmol/L)
|
4.3 Percentage
|
6.7 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Protein (g/dL)
|
2.7 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Pseudocholinesterase (U/mL)
|
2.1 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Sodium (mmol/L)
|
1.4 Percentage
|
3.9 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Triacylglycerol lipase (U/L)
|
18.8 Percentage
|
18.8 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Urate (mg/dL)
|
13.6 Percentage
|
35.7 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Urea (mg/dL)
|
22.9 Percentage
|
36.7 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
eGFR MDRD method(mL/min/1.73 m2)
|
0.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
Creatinine clearance (mL/min)
|
11.5 Percentage
|
8.6 Percentage
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit, and for each parameter.
Frequency of participants per treatment group only with a treatment-emergent shift in clinical chemistry parameters from normal or high at baseline to a low value at a timepoint after the start of treatment. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=147 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=77 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Albumin (g/dL)
|
2.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Alkaline phosphatase (U/L)
|
2.1 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Bilirubin (mg/dL)
|
0.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Calcium (mg/dL)
|
14.3 Percentage
|
6.3 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Creatine kinase (U/L)
|
6.4 Percentage
|
6.8 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Creatinine (mg/dL)
|
4.1 Percentage
|
3.9 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Gamma glutamyltransferase (U/L)
|
0.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Phosphate (mg/dL)
|
10.5 Percentage
|
9.5 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Potassium (mmol/L)
|
18.4 Percentage
|
18.9 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Protein (g/dL)
|
6.3 Percentage
|
2.8 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Pseudocholinesterase (U/mL)
|
10.0 Percentage
|
14.7 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Sodium (mmol/L)
|
4.3 Percentage
|
6.6 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Triacylglycerol lipase (U/L)
|
0.0 Percentage
|
0.0 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Urate (mg/dL)
|
2.7 Percentage
|
2.6 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Urea (mg/dL)
|
0.0 Percentage
|
1.3 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
eGFR MDRDmethod (mL/min/1.73 m2)
|
26.7 Percentage
|
22.4 Percentage
|
|
Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
Creatinine clearance (mL/min)
|
29.2 Percentage
|
40.6 Percentage
|
SECONDARY outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
Urate is standard clinical chemistry parameter. A termination visit was only to be performed in the case of premature termination of study medication or if the sponsor announced the official end of the study.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=147 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=77 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change From Baseline of Urate in Clinical Chemistry
Baseline (Week 0)
|
6.767 milligram/deciliter (mg/dL)
Standard Deviation 1.859
|
6.999 milligram/deciliter (mg/dL)
Standard Deviation 2.193
|
|
Change From Baseline of Urate in Clinical Chemistry
Change from baseline to Termination visit
|
0.310 milligram/deciliter (mg/dL)
Standard Deviation 2.916
|
-1.290 milligram/deciliter (mg/dL)
Standard Deviation 1.120
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Systolic Blood Pressure (SBP)
Baseline (Week 0)
|
118.81 millimetre(s) of mercury (mmHg)
Standard Deviation 14.96
|
124.26 millimetre(s) of mercury (mmHg)
Standard Deviation 16.14
|
|
Change of Systolic Blood Pressure (SBP)
Change from baseline to Termination visit
|
-3.96 millimetre(s) of mercury (mmHg)
Standard Deviation 17.34
|
-5.02 millimetre(s) of mercury (mmHg)
Standard Deviation 14.79
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Diastolic Blood Pressure (DBP)
Baseline (Week 0)
|
75.34 mmHg
Standard Deviation 9.75
|
78.55 mmHg
Standard Deviation 9.46
|
|
Change of Diastolic Blood Pressure (DBP)
Change from baseline to Termination visit
|
-6.16 mmHg
Standard Deviation 13.77
|
-7.26 mmHg
Standard Deviation 11.09
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Heart Rate
Baseline (Week 0)
|
77.66 beats/minute (BPM)
Standard Deviation 12.12
|
76.11 beats/minute (BPM)
Standard Deviation 12.10
|
|
Change of Heart Rate
Change from baseline to Termination visit
|
-0.89 beats/minute (BPM)
Standard Deviation 13.85
|
3.77 beats/minute (BPM)
Standard Deviation 14.69
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Weight
Baseline (Week 0)
|
74.01 kilogram (kg)
Standard Deviation 18.76
|
77.29 kilogram (kg)
Standard Deviation 16.42
|
|
Change of Weight
From baseline to Termination visit
|
-0.87 kilogram (kg)
Standard Deviation 5.86
|
-2.97 kilogram (kg)
Standard Deviation 7.27
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=154 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=81 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Oxygen Saturation (SaO2)
Baseline (Week 0)
|
93.9 Percentage
Standard Deviation 2.7
|
93.6 Percentage
Standard Deviation 2.4
|
|
Change of Oxygen Saturation (SaO2)
From baseline to Termination visit
|
0.0 Percentage
Standard Deviation 2.6
|
-2.3 Percentage
Standard Deviation 5.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=154 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=81 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Arterial Partial Oxygen Pressure (PaO2)
Baseline (Week 0)
|
69.66 mmHg
Standard Deviation 11.90
|
69.19 mmHg
Standard Deviation 10.96
|
|
Change of Arterial Partial Oxygen Pressure (PaO2)
From baseline to Termination visit
|
-1.67 mmHg
Standard Deviation 8.02
|
2.00 mmHg
Standard Deviation 24.73
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Termination visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=154 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=81 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
Baseline (Week 0)
|
33.20 mmHg
Standard Deviation 4.61
|
33.52 mmHg
Standard Deviation 4.60
|
|
Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
From baseline to Termination visit
|
-0.33 mmHg
Standard Deviation 1.53
|
-2.25 mmHg
Standard Deviation 4.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Month 48Population: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=149 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=75 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of RR Duration From Electrocardiogram (ECG)
Baseline (Week 0)
|
812.90 millisecond (msec)
Standard Deviation 144.31
|
828.47 millisecond (msec)
Standard Deviation 147.54
|
|
Change of RR Duration From Electrocardiogram (ECG)
Change rom baseline to Month 48
|
152.00 millisecond (msec)
Standard Deviation 236.17
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Month 48Population: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=147 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=72 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of PR Duration From ECG
Baseline (Week 0)
|
173.22 msec
Standard Deviation 26.49
|
174.92 msec
Standard Deviation 24.35
|
|
Change of PR Duration From ECG
Change from baseline to Month 48
|
-10.00 msec
Standard Deviation 11.31
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Month 48Population: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=148 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=74 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of QRS Duration From ECG
Baseline (Week 0)
|
104.30 msec
Standard Deviation 17.85
|
104.11 msec
Standard Deviation 18.24
|
|
Change of QRS Duration From ECG
Change from baseline to Month 48
|
3.00 msec
Standard Deviation 4.24
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Month 48Population: Participants in SAF with evaluable data for each visit
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.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=114 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=53 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change of QT Duration in ECG
Baseline (Week 0)
|
405.82 msec
Standard Deviation 31.29
|
408.45 msec
Standard Deviation 30.98
|
|
Change of QT Duration in ECG
Change from baseline to Month 48
|
42.00 msec
Standard Deviation 39.60
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
6MWD is exercise testing and is one of efficacy evaluation
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in Six-minute Walking Distance (6MWD) Test
Baseline (Week 0)
|
361.0 meters
Interval 150.0 to 557.0
|
372.0 meters
Interval 170.0 to 474.0
|
|
Change in Six-minute Walking Distance (6MWD) Test
Change from baseline to End of study visit
|
31.0 meters
Interval -447.0 to 230.0
|
12.5 meters
Interval -448.0 to 215.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Month 45 and Month 48Population: Participants in SAF with evaluable data for each visit
Pulmonary vascular resistance (PVR) was measured only if right-heart catheterization was performed as part of a regular diagnostic work-up. Analyses up to Month 48 due to limited data.
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=146 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=80 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in Pulmonary Vascular Resistance (PVR)
Baseline (Week 0)
|
796.64 dyn*s*cm^-5
Standard Deviation 435.24
|
761.83 dyn*s*cm^-5
Standard Deviation 388.87
|
|
Change in Pulmonary Vascular Resistance (PVR)
Change from baseline to Month 45
|
—
|
-1243.48 dyn*s*cm^-5
Standard Deviation NA
The value was not calculated due to very low number of participants
|
|
Change in Pulmonary Vascular Resistance (PVR)
Change from baseline to Month 48
|
-148.29 dyn*s*cm^-5
Standard Deviation 74.39
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=135 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=69 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
Baseline (Week 0)
|
1553.19 picograms/millilitre (pg/mL)
Standard Deviation 2435.94
|
1404.23 picograms/millilitre (pg/mL)
Standard Deviation 1745.48
|
|
Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
Change from baseline to End of study visit
|
-125.99 picograms/millilitre (pg/mL)
Standard Deviation 2503.78
|
-187.96 picograms/millilitre (pg/mL)
Standard Deviation 1438.96
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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).
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in World Health Organization (WHO) Functional Class
Baseline (Week 0)-class I
|
3 Participants
|
0 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Baseline (Week 0)-class II
|
48 Participants
|
25 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Baseline (Week 0)-class III
|
100 Participants
|
54 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Baseline (Week 0)-class IV
|
4 Participants
|
2 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Baseline (Week 0)-Missing
|
0 Participants
|
1 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- -2
|
7 Participants
|
4 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- -1
|
44 Participants
|
24 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- -0
|
72 Participants
|
38 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- +1
|
11 Participants
|
2 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- +2
|
13 Participants
|
7 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- +3
|
7 Participants
|
6 Participants
|
|
Change in World Health Organization (WHO) Functional Class
Change from baseline to End of study visit- +4
|
1 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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).
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Number of Participants With Clinical Worsening
Any clinical worsening
|
45 Participants
|
23 Participants
|
|
Number of Participants With Clinical Worsening
Pulmonary endarterectomy
|
4 Participants
|
3 Participants
|
|
Number of Participants With Clinical Worsening
Hospitalization due to PH
|
7 Participants
|
3 Participants
|
|
Number of Participants With Clinical Worsening
Start of new PH treatment
|
21 Participants
|
9 Participants
|
|
Number of Participants With Clinical Worsening
Decrease in 6MWD due to PH
|
4 Participants
|
2 Participants
|
|
Number of Participants With Clinical Worsening
Persistent worsening of functional class due to PH
|
7 Participants
|
2 Participants
|
|
Number of Participants With Clinical Worsening
Death
|
22 Participants
|
13 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsTime 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).
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Persistent worsening of functional class due to PH
|
1.28 Percentage per 100 person-years
|
0.69 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Any clinical worsening event
|
12.84 Percentage per 100 person-years
|
11.77 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Pulmonary endarterectomy
|
0.73 Percentage per 100 person-years
|
1.04 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Hospitalization due to PH
|
1.65 Percentage per 100 person-years
|
1.04 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Start of new PH treatment
|
4.40 Percentage per 100 person-years
|
3.81 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Decrease in 6MWD due to PH
|
0.73 Percentage per 100 person-years
|
0.69 Percentage per 100 person-years
|
|
Incidence of Clinical Worsening Events Per 100 Person Years
Death
|
4.04 Percentage per 100 person-years
|
4.50 Percentage per 100 person-years
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to Week 12Population: Participants in SAF with evaluable data for each visit
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").
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=155 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=82 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change From Baseline in Borg CR 10 Scale
Baseline (Week 0)
|
4.36 Scores on a scale
Standard Deviation 2.30
|
4.45 Scores on a scale
Standard Deviation 2.26
|
|
Change From Baseline in Borg CR 10 Scale
Change from baseline to Week 12
|
-0.93 Scores on a scale
Standard Deviation 2.47
|
-0.3 Scores on a scale
Standard Deviation 2.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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).
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=154 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=81 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in Score of EQ-5D Questionnaire
Baseline (Week 0)
|
0.6406 Scores on a scale
Standard Deviation 0.2509
|
0.6569 Scores on a scale
Standard Deviation 0.2518
|
|
Change in Score of EQ-5D Questionnaire
Change from baseline to EOS Visit
|
-0.1008 Scores on a scale
Standard Deviation 0.4965
|
-0.1230 Scores on a scale
Standard Deviation 0.5213
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From baseline to End of study visit, up to 10 yearsPopulation: Participants in SAF with evaluable data for each visit
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).
Outcome measures
| Measure |
Riociguat-Former Riociguat 1.0-2.5 mg
n=152 Participants
Participants were from the former riociguat (BAY 63-2521) treatment group of CHEST-1 on the same dose as they received on the last day of CHEST-1.
|
Riociguat-Former Placebo
n=80 Participants
Participants were from the former placebo group of CHEST-1. The starting dose in CHEST-2 was 1.0 mg riociguat three times one day.
|
|---|---|---|
|
Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire
Baseline (Week 0)
|
42.19 Scores on a scale
Standard Deviation 22.05
|
46.01 Scores on a scale
Standard Deviation 22.93
|
|
Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire
Change from baseline to EOS Visit
|
-2.64 Scores on a scale
Standard Deviation 29.26
|
-0.56 Scores on a scale
Standard Deviation 30.83
|
Adverse Events
Former Riociguat 1.0-2.5 mg
Serious events: 96 serious events
Other events: 148 other events
Deaths: 22 deaths
Former Placebo
Serious events: 56 serious events
Other events: 79 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Former Riociguat 1.0-2.5 mg
n=155 participants at risk
Subjects from the riociguat 1.0-2.5 mg group of CHEST-1 entered the extension study(CHEST-2) with the same dose as they received on the last day of CHEST-1 (Visit7).
|
Former Placebo
n=82 participants at risk
Subjects from the placebo group of CHEST-1 entered the extension study (CHEST-2),the starting dose in CHEST-2 was 1.0 mg riociguat tid.
|
|---|---|---|
|
Nervous system disorders
Syncope
|
9.0%
14/155 • Number of events 16 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
13.4%
11/82 • Number of events 17 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Vertebrobasilar stroke
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Psychiatric disorders
Bipolar I disorder
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Psychiatric disorders
Psychiatric decompensation
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Psychiatric disorders
Vascular cognitive impairment
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Blood and lymphatic system disorders
Anaemia
|
2.6%
4/155 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Blood and lymphatic system disorders
Bicytopenia
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Angina unstable
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Arrhythmia
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Atrial fibrillation
|
3.2%
5/155 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Atrial flutter
|
3.2%
5/155 • Number of events 7 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Atrial tachycardia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardiac arrest
|
3.2%
5/155 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardiac failure
|
5.2%
8/155 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardiac failure acute
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cardiogenic shock
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Cor pulmonale chronic
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Coronary artery disease
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Prinzmetal angina
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Right ventricular failure
|
8.4%
13/155 • Number of events 24 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 13 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Acute coronary syndrome
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Acute right ventricular failure
|
1.9%
3/155 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Endocrine disorders
Myxoedema
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Eye disorders
Glaucoma
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Eye disorders
Retinal detachment
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Eye disorders
Vitreous haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Ascites
|
0.65%
1/155 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.65%
1/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Food poisoning
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
3.9%
6/155 • Number of events 7 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Incarcerated inguinal hernia
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Melaena
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Nausea
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.3%
2/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Asthenia
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Chest pain
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Death
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Fatigue
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Generalised oedema
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Oedema peripheral
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Pelvic mass
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Sudden death
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Sudden cardiac death
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
General physical health deterioration
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Hepatobiliary disorders
Bile duct stone
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Appendicitis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Bronchitis
|
1.3%
2/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Erysipelas
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Gastroenteritis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Infection
|
1.3%
2/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Lymphangitis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Pneumonia
|
11.0%
17/155 • Number of events 20 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Sepsis
|
1.9%
3/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Septic shock
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Tonsillitis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Urinary tract infection
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Urosepsis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Subdiaphragmatic abscess
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Lung infection
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Respiratory tract infection
|
1.9%
3/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Bone abscess
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Fall
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Angiogram pulmonary
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Blood creatinine increased
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Catheterisation cardiac
|
5.2%
8/155 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Colonoscopy
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
International normalised ratio increased
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Investigation
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Gout
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Steroid diabetes
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.9%
3/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal neoplasm
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Dementia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Dizziness
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Azotaemia
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Haematuria
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Renal failure
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Urinary incontinence
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Chronic kidney disease
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Renal and urinary disorders
Acute kidney injury
|
1.9%
3/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Reproductive system and breast disorders
Bartholin's cyst
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Reproductive system and breast disorders
Adenomyosis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.6%
4/155 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Non-cardiogenic pulmonary oedema
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
10.3%
16/155 • Number of events 29 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
15.9%
13/82 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
2.6%
4/155 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.65%
1/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Angioplasty
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Cholecystectomy
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Colostomy
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Peritoneal dialysis
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Removal of internal fixation
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Splenectomy
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Transurethral prostatectomy
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Vitrectomy
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Vena cava filter insertion
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Hysterosalpingo-oophorectomy
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Knee operation
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Hospitalisation
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Cervical conisation
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Cardiac ablation
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Pulmonary artery therapeutic procedure
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Cataract operation
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Surgical and medical procedures
Pulmonary endarterectomy
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Haematoma
|
1.3%
2/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Hypotension
|
1.9%
3/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Temporal arteritis
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Shock haemorrhagic
|
0.65%
1/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
0.00%
0/82 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/155 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Product Issues
Device dislocation
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
1.2%
1/82 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
Other adverse events
| Measure |
Former Riociguat 1.0-2.5 mg
n=155 participants at risk
Subjects from the riociguat 1.0-2.5 mg group of CHEST-1 entered the extension study(CHEST-2) with the same dose as they received on the last day of CHEST-1 (Visit7).
|
Former Placebo
n=82 participants at risk
Subjects from the placebo group of CHEST-1 entered the extension study (CHEST-2),the starting dose in CHEST-2 was 1.0 mg riociguat tid.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.7%
15/155 • Number of events 24 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Atrial fibrillation
|
7.7%
12/155 • Number of events 13 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Palpitations
|
8.4%
13/155 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Supraventricular extrasystoles
|
1.3%
2/155 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Cardiac disorders
Ventricular extrasystoles
|
2.6%
4/155 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.2%
8/155 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.4%
13/155 • Number of events 16 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Constipation
|
9.0%
14/155 • Number of events 17 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Diarrhoea
|
19.4%
30/155 • Number of events 37 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
20.7%
17/82 • Number of events 27 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.0%
17/155 • Number of events 22 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
13.4%
11/82 • Number of events 12 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastritis
|
2.6%
4/155 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.8%
9/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
4.9%
4/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Nausea
|
12.3%
19/155 • Number of events 23 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
19.5%
16/82 • Number of events 27 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Toothache
|
6.5%
10/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
4.9%
4/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Gastrointestinal disorders
Vomiting
|
9.7%
15/155 • Number of events 19 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Chest discomfort
|
4.5%
7/155 • Number of events 12 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Chest pain
|
9.7%
15/155 • Number of events 20 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Fatigue
|
6.5%
10/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Oedema
|
3.9%
6/155 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 13 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Oedema peripheral
|
24.5%
38/155 • Number of events 58 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
32.9%
27/82 • Number of events 40 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
General disorders
Pyrexia
|
5.8%
9/155 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
4.9%
4/82 • Number of events 7 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Bronchitis
|
15.5%
24/155 • Number of events 39 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
13.4%
11/82 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Influenza
|
4.5%
7/155 • Number of events 7 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Nasopharyngitis
|
35.5%
55/155 • Number of events 108 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
29.3%
24/82 • Number of events 47 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Pneumonia
|
7.1%
11/155 • Number of events 12 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
4.9%
4/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Upper respiratory tract infection
|
16.8%
26/155 • Number of events 32 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
15.9%
13/82 • Number of events 25 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Urinary tract infection
|
9.7%
15/155 • Number of events 24 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Infections and infestations
Respiratory tract infection
|
7.7%
12/155 • Number of events 27 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 17 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Fall
|
2.6%
4/155 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
5.8%
9/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Injury, poisoning and procedural complications
Contusion
|
7.7%
12/155 • Number of events 16 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
6.5%
10/155 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
2.4%
2/82 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
Blood potassium decreased
|
0.65%
1/155 • Number of events 1 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Investigations
International normalised ratio increased
|
8.4%
13/155 • Number of events 19 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
3.2%
5/155 • Number of events 5 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.3%
16/155 • Number of events 20 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 14 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.9%
6/155 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
18.1%
28/155 • Number of events 33 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
12.2%
10/82 • Number of events 19 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.4%
27/155 • Number of events 40 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
13.4%
11/82 • Number of events 14 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.2%
8/155 • Number of events 12 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
4.9%
4/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.2%
8/155 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
6.1%
5/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.3%
16/155 • Number of events 16 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
9.8%
8/82 • Number of events 11 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Dizziness
|
21.9%
34/155 • Number of events 47 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
24.4%
20/82 • Number of events 28 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Nervous system disorders
Headache
|
9.0%
14/155 • Number of events 19 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
14.6%
12/82 • Number of events 21 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Psychiatric disorders
Insomnia
|
5.2%
8/155 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.4%
27/155 • Number of events 34 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
20.7%
17/82 • Number of events 23 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.1%
25/155 • Number of events 29 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
18.3%
15/82 • Number of events 23 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.0%
17/155 • Number of events 20 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
13.4%
11/82 • Number of events 15 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.2%
8/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.2%
8/155 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
11.0%
9/82 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.2%
8/155 • Number of events 9 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 4 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
5.2%
8/155 • Number of events 16 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
8.5%
7/82 • Number of events 8 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.8%
9/155 • Number of events 10 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
3.7%
3/82 • Number of events 3 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.3%
2/155 • Number of events 2 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
7.3%
6/82 • Number of events 6 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
|
Vascular disorders
Hypotension
|
7.7%
12/155 • Number of events 13 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
12.2%
10/82 • Number of events 13 • From administration of first dose of study medication up to 2 days after end of treatment with study medication, up to 10 years.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER