Trial Outcomes & Findings for Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma (NCT NCT01774344)
NCT ID: NCT01774344
Last Updated: 2020-08-20
Results Overview
Overall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
573 participants
Primary outcome timeframe
From randomization (Day 1) of the first subject until 419 days later
Results posted on
2020-08-20
Participant Flow
The study was conducted between 14 May 2013 (first subject first visit), 29 February 2016 (primary completion date) and 05-July-2019 (Last Patient Last Visit =End of study).
Overall, 843 subjects were screened, of them 270 subjects were screening failures. 573 subjects were randomized and assigned to treatment; of them 6 subjects never received treatment. 436 Entered survival Follow-up and 4 End of survival follow-up data not available.
Participant milestones
| Measure |
Placebo
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Overall Study
STARTED
|
194
|
379
|
|
Overall Study
Treated
|
193
|
374
|
|
Overall Study
Entered Survival FU
|
145
|
291
|
|
Overall Study
COMPLETED
|
132
|
258
|
|
Overall Study
NOT COMPLETED
|
62
|
121
|
Reasons for withdrawal
| Measure |
Placebo
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
10
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
10
|
|
Overall Study
End of survival follow-up not available
|
2
|
2
|
|
Overall Study
Data collection finished
|
4
|
14
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Did not enter Survival Follow up
|
49
|
83
|
Baseline Characteristics
Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best supportive care (BSC).
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
Total
n=573 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.1 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
61.8 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
61.6 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
171 Participants
n=5 Participants
|
333 Participants
n=7 Participants
|
504 Participants
n=5 Participants
|
|
Eastern cooperative oncology group (ECOG) Performance Status (PS) (data collection system-RAVE)
ECOG PS 0
|
130 Participants
n=5 Participants
|
247 Participants
n=7 Participants
|
377 Participants
n=5 Participants
|
|
Eastern cooperative oncology group (ECOG) Performance Status (PS) (data collection system-RAVE)
ECOG PS 1
|
64 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
196 Participants
n=5 Participants
|
|
ECOG PS: Interactive voice response system (IVRS)
ECOG PS 0
|
129 Participants
n=5 Participants
|
251 Participants
n=7 Participants
|
380 Participants
n=5 Participants
|
|
ECOG PS: Interactive voice response system (IVRS)
ECOG PS 1
|
65 Participants
n=5 Participants
|
128 Participants
n=7 Participants
|
193 Participants
n=5 Participants
|
|
Alpha-fetoprotein (AFP) (RAVE)
less than (<) 400 nanogram per milliliter (ng/mL)
|
107 Participants
n=5 Participants
|
217 Participants
n=7 Participants
|
324 Participants
n=5 Participants
|
|
Alpha-fetoprotein (AFP) (RAVE)
greater than or equal to (>=) 400 ng/mL
|
87 Participants
n=5 Participants
|
162 Participants
n=7 Participants
|
249 Participants
n=5 Participants
|
|
Alpha-fetoprotein (AFP) (IVRS)
< 400 ng/mL
|
105 Participants
n=5 Participants
|
212 Participants
n=7 Participants
|
317 Participants
n=5 Participants
|
|
Alpha-fetoprotein (AFP) (IVRS)
>= 400 ng/mL
|
89 Participants
n=5 Participants
|
167 Participants
n=7 Participants
|
256 Participants
n=5 Participants
|
|
Macrovascular invasion (RAVE)
Absence
|
140 Participants
n=5 Participants
|
269 Participants
n=7 Participants
|
409 Participants
n=5 Participants
|
|
Macrovascular invasion (RAVE)
Presence
|
54 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
164 Participants
n=5 Participants
|
|
Macrovascular invasion (IVRS)
Absence
|
135 Participants
n=5 Participants
|
262 Participants
n=7 Participants
|
397 Participants
n=5 Participants
|
|
Macrovascular invasion (IVRS)
Presence
|
59 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
The Barcelona-Clinic Liver Cancer (BCLC) stage at study entry
Early stage
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
The Barcelona-Clinic Liver Cancer (BCLC) stage at study entry
Intermediate stage
|
22 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
The Barcelona-Clinic Liver Cancer (BCLC) stage at study entry
Advanced stage
|
172 Participants
n=5 Participants
|
325 Participants
n=7 Participants
|
497 Participants
n=5 Participants
|
|
Extrahepatic disease (RAVE)
Absence
|
47 Participants
n=5 Participants
|
114 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Extrahepatic disease (RAVE)
Presence
|
147 Participants
n=5 Participants
|
265 Participants
n=7 Participants
|
412 Participants
n=5 Participants
|
|
Extrahepatic disease (IVRS)
Absence
|
62 Participants
n=5 Participants
|
129 Participants
n=7 Participants
|
191 Participants
n=5 Participants
|
|
Extrahepatic disease (IVRS)
Presence
|
132 Participants
n=5 Participants
|
250 Participants
n=7 Participants
|
382 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization (Day 1) of the first subject until 419 days laterOverall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Overall Survival (OS)
|
237 days
95% Confidence Interval 192 • Interval 192.0 to 269.0
|
323 days
95% Confidence Interval 276 • Interval 276.0 to 369.0
|
SECONDARY outcome
Timeframe: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)TTP was the time (days) from randomization to radiological or clinical disease progression assessed by independent radiological review. Median and 95% confidence interval were reported for the modified response evaluation criteria in solid tumors (mRECIST) and response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) analysis sets. Subjects still alive at the time of analysis were censored at their last date of last contact.
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Time to Progression (TTP)
mRECIST
|
45 days
95% Confidence Interval 44 • Interval 44.0 to 49.0
|
97 days
95% Confidence Interval 87 • Interval 87.0 to 128.0
|
|
Time to Progression (TTP)
RECIST 1.1
|
45 days
95% Confidence Interval 44 • Interval 44.0 to 49.0
|
119 days
95% Confidence Interval 87 • Interval 87.0 to 128.0
|
SECONDARY outcome
Timeframe: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks)Progression Free Survival (PFS) was defined as the time (days) from date of randomization to date of disease progression (radiological or clinical) or death due to any cause, if death occurs before progression was documented. Death in the absence of progression was a PFS event only if it occurred within the 12+1 weeks for subjects who discontinued treatment prior to cycle 8 and 24+2 weeks for subjects who discontinued treatment after to cycle 8 of the last evaluable tumor assessment; PFS were censored at the date of the last evaluable tumor assessment, if it occurred later. Median and 95% confidence interval 95% were reported for the mRECIST and RECIST 1.1 analysis sets. Subjects still alive at the time of analysis were censored at their last date of last contact.
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Progression Free Survival (PFS)
mRECIST
|
45 days
95% Confidence Interval 44 • Interval 44.0 to 47.0
|
95 days
95% Confidence Interval 86 • Interval 86.0 to 127.0
|
|
Progression Free Survival (PFS)
RECIST 1.1
|
45 days
95% Confidence Interval 44 • Interval 44.0 to 49.0
|
102 days
95% Confidence Interval 87 • Interval 87.0 to 127.0
|
SECONDARY outcome
Timeframe: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)Objective tumor response rate (ORR) was defined as the percentage of subjects whose best tumor response CR or Partial Response (PR) observed during trial period assessed according to the mRECIST criteria and RECIST 1.1. CR= Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Subjects prematurely discontinuing without an assessment were to be considered non-responders for the analysis.
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Objective Tumor Response Rate (ORR)
mRECIST
|
4.1 percentage of subjects
|
10.8 percentage of subjects
|
|
Objective Tumor Response Rate (ORR)
RECIST 1.1
|
2.6 percentage of subjects
|
6.6 percentage of subjects
|
SECONDARY outcome
Timeframe: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)Disease control rate (DCR) was defined as the percentage of subjects whose best response was CR (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), PR (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or stable disease (SD) (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST and RECIST 1.1 criteria. SD had to be maintained for at least 6 weeks from the first demonstration of that rating.
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Disease Control Rate (DCR)
mRECIST
|
36.1 percentage of subjects
|
65.2 percentage of subjects
|
|
Disease Control Rate (DCR)
RECIST 1.1
|
34.5 percentage of subjects
|
65.7 percentage of subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From randomization (Day 1) of the first subject to end of follow upto 1710 daysOverall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause
Outcome measures
| Measure |
Placebo
n=194 Participants
Subjects received placebo matched to regorafenib coated tablets orally every day for 3 weeks followed by 1 week off treatment plus best best supportive care.
|
Regorafenib 160 mg (BAY73-4506)
n=379 Participants
Subjects received regorafenib 160 milligram (mg) (4 \* 40 mg coated tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Overall Survival (OS)
|
241 days
95% Confidence Interval 196 • Interval 196.0 to 274.0
|
326 days
95% Confidence Interval 278 • Interval 278.0 to 372.0
|
Adverse Events
Placebo
Serious events: 92 serious events
Other events: 162 other events
Deaths: 176 deaths
Regorafenib (Stivarga, BAY73-4506)
Serious events: 194 serious events
Other events: 366 other events
Deaths: 324 deaths
Serious adverse events
| Measure |
Placebo
n=193 participants at risk
Description: Subjects received placebo matched to regorafenib tablets orally every day for 3 weeks followed by 1 week off treatment plus best supportive care(BSC).
|
Regorafenib (Stivarga, BAY73-4506)
n=374 participants at risk
Description: Subjects received regorafenib 160 mg (4 \*40 mg tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.52%
1/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 9 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 7 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Cardiac arrest
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Eye disorders
Retinal artery occlusion
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal distension
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
4/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Ascites
|
3.1%
6/193 • Number of events 7 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
2.7%
10/374 • Number of events 13 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Duodenal perforation
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Gastritis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.0%
2/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Haematemesis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
1.0%
2/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.6%
6/374 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.6%
3/193 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.6%
6/374 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Asthenia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Death
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Fatigue
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
General physical health deterioration
|
13.0%
25/193 • Number of events 32 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
12.6%
47/374 • Number of events 73 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Malaise
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Pain
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Pyrexia
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.6%
6/374 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Bile duct stenosis
|
1.0%
2/193 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Cholangitis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatic failure
|
4.7%
9/193 • Number of events 14 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
2.4%
9/374 • Number of events 14 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
1.6%
3/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
1.0%
2/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatobiliary disease
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hepatorenal syndrome
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.52%
1/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Jaundice
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Bronchitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Candida infection
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Cellulitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Liver abscess
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Lung abscess
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Lung infection
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Peritonitis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Pleural infection bacterial
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Pneumonia
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
2.1%
8/374 • Number of events 11 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Sepsis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Septic shock
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Streptococcal bacteraemia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Subcutaneous abscess
|
0.52%
1/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Tracheitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Urosepsis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Wound infection bacterial
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Blood bilirubin increased
|
1.0%
2/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Blood pressure decreased
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
General physical condition abnormal
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.6%
3/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.0%
2/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.6%
6/374 • Number of events 9 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine benign neoplasm
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Cerebral haematoma
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Encephalopathy
|
1.6%
3/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Headache
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Hemiparesis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Hepatic encephalopathy
|
1.6%
3/193 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
2.4%
9/374 • Number of events 14 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Meningorrhagia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Myasthenia gravis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Quadriparesis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Sciatica
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Seizure
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Syncope
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Acute kidney injury
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Cystitis noninfective
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Renal failure
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
2/193 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.3%
5/374 • Number of events 7 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.0%
2/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
1.1%
4/374 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.6%
3/193 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal disorder
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Deep vein thrombosis
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Embolism
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.80%
3/374 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Orthostatic hypotension
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Blood and lymphatic system disorders
Blood loss anaemia
|
0.52%
1/193 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.53%
2/374 • Number of events 3 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Eye disorders
Cataract
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Infections and infestations
Folliculitis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Diplegia
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Intracranial pressure increased
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 2 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Intracranial venous sinus thrombosis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Reproductive system and breast disorders
Scrotal oedema
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary venous thrombosis
|
0.00%
0/193 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.27%
1/374 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Precancerous skin lesion
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
0.00%
0/374 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
Other adverse events
| Measure |
Placebo
n=193 participants at risk
Description: Subjects received placebo matched to regorafenib tablets orally every day for 3 weeks followed by 1 week off treatment plus best supportive care(BSC).
|
Regorafenib (Stivarga, BAY73-4506)
n=374 participants at risk
Description: Subjects received regorafenib 160 mg (4 \*40 mg tablets) orally every day for 3 weeks followed by 1 week off treatment plus BSC.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.9%
21/193 • Number of events 40 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
15.2%
57/374 • Number of events 114 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Endocrine disorders
Hypothyroidism
|
0.52%
1/193 • Number of events 1 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
7.8%
29/374 • Number of events 33 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal distension
|
5.2%
10/193 • Number of events 13 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.3%
20/374 • Number of events 24 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.3%
18/193 • Number of events 22 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
13.9%
52/374 • Number of events 85 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Abdominal pain
|
15.0%
29/193 • Number of events 43 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
22.7%
85/374 • Number of events 127 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Ascites
|
16.1%
31/193 • Number of events 57 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
16.3%
61/374 • Number of events 91 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Constipation
|
10.9%
21/193 • Number of events 24 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
17.9%
67/374 • Number of events 79 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Diarrhoea
|
16.1%
31/193 • Number of events 44 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
43.6%
163/374 • Number of events 348 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Dry mouth
|
6.2%
12/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.9%
22/374 • Number of events 24 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Nausea
|
13.5%
26/193 • Number of events 38 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
19.3%
72/374 • Number of events 106 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Stomatitis
|
2.1%
4/193 • Number of events 4 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
8.3%
31/374 • Number of events 44 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
13/193 • Number of events 17 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
13.4%
50/374 • Number of events 73 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Asthenia
|
9.8%
19/193 • Number of events 34 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
15.0%
56/374 • Number of events 97 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Fatigue
|
25.9%
50/193 • Number of events 67 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
29.4%
110/374 • Number of events 205 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Malaise
|
2.6%
5/193 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
6.1%
23/374 • Number of events 33 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Oedema peripheral
|
13.5%
26/193 • Number of events 32 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
16.8%
63/374 • Number of events 81 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
General disorders
Pyrexia
|
6.7%
13/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
21.1%
79/374 • Number of events 113 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Alanine aminotransferase increased
|
10.9%
21/193 • Number of events 37 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
15.0%
56/374 • Number of events 102 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Blood alkaline phosphatase increased
|
4.7%
9/193 • Number of events 21 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
6.1%
23/374 • Number of events 43 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Aspartate aminotransferase increased
|
20.7%
40/193 • Number of events 89 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
26.5%
99/374 • Number of events 234 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Blood bilirubin increased
|
15.5%
30/193 • Number of events 59 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
25.1%
94/374 • Number of events 258 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Gamma-glutamyltransferase increased
|
7.3%
14/193 • Number of events 32 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
6.4%
24/374 • Number of events 73 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Lipase increased
|
3.6%
7/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
7.2%
27/374 • Number of events 62 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Platelet count decreased
|
1.0%
2/193 • Number of events 8 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
10.4%
39/374 • Number of events 129 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
Weight decreased
|
4.7%
9/193 • Number of events 11 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
14.7%
55/374 • Number of events 132 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.0%
29/193 • Number of events 37 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
32.6%
122/374 • Number of events 186 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
7.3%
14/193 • Number of events 19 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
15.0%
56/374 • Number of events 152 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.1%
6/193 • Number of events 22 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
7.5%
28/374 • Number of events 62 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.6%
7/193 • Number of events 17 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.3%
20/374 • Number of events 30 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.7%
11/193 • Number of events 12 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
4.0%
15/374 • Number of events 17 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
2.6%
5/193 • Number of events 11 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
9.6%
36/374 • Number of events 96 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
16/193 • Number of events 18 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
13.4%
50/374 • Number of events 73 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.7%
11/193 • Number of events 19 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
4.8%
18/374 • Number of events 22 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.1%
4/193 • Number of events 5 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
10.2%
38/374 • Number of events 48 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.6%
5/193 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
8.3%
31/374 • Number of events 51 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Nervous system disorders
Headache
|
6.2%
12/193 • Number of events 12 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
6.7%
25/374 • Number of events 33 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Psychiatric disorders
Insomnia
|
4.1%
8/193 • Number of events 8 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
8.0%
30/374 • Number of events 35 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Renal and urinary disorders
Proteinuria
|
1.0%
2/193 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
9.1%
34/374 • Number of events 96 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
13/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
12.0%
45/374 • Number of events 50 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.8%
15/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
7.0%
26/374 • Number of events 42 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
2.6%
5/193 • Number of events 7 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
18.2%
68/374 • Number of events 85 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.2%
10/193 • Number of events 11 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
3.5%
13/374 • Number of events 14 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.1%
6/193 • Number of events 6 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
7.2%
27/374 • Number of events 27 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
7.8%
15/193 • Number of events 27 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
51.9%
194/374 • Number of events 554 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.3%
14/193 • Number of events 19 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.9%
22/374 • Number of events 34 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.3%
14/193 • Number of events 15 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.6%
21/374 • Number of events 28 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Vascular disorders
Hypertension
|
7.3%
14/193 • Number of events 30 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
31.8%
119/374 • Number of events 327 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
|
Investigations
White blood cell count decreased
|
1.0%
2/193 • Number of events 7 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
5.3%
20/374 • Number of events 40 • Adverse event data were collected after start of study drug administration until 30 days after end of study treatment over a period of approximately three years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60