Trial Outcomes & Findings for Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC) (NCT NCT00946153)
NCT ID: NCT00946153
Last Updated: 2019-02-01
Results Overview
The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (\>) 10.0\*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria \>3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
66 participants
Primary outcome timeframe
Up to 28 days (Cycle1)
Results posted on
2019-02-01
Participant Flow
Participants took part in the study at 12 sites in Japan and 2 sites in South Korea from 24 Jul 2009 to 13 Aug 2015.
Participant milestones
| Measure |
Phase 1: Group 1: Lenvatinib: 12 mg
Participants with child-pugh (CP) scores of 5 or 6 received a starting dose of 12 milligram (mg) (three 4 mg tablets) lenvatinib orally once daily (QD) in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.
|
Phase 1: Group 1: Lenvatinib: 16 mg
Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 2: Lenvatinib: 12 mg
Participants with CP scores of 5 or 6 received recommended dose (RD) of 12 mg (three 4 mg tablets) lenvatinib established from group 1, in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|---|
|
Phase 1
STARTED
|
6
|
3
|
6
|
5
|
0
|
|
Phase 1
COMPLETED
|
6
|
3
|
6
|
5
|
0
|
|
Phase 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2
STARTED
|
0
|
0
|
0
|
0
|
46
|
|
Phase 2
COMPLETED
|
0
|
0
|
0
|
0
|
33
|
|
Phase 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
13
|
Reasons for withdrawal
| Measure |
Phase 1: Group 1: Lenvatinib: 12 mg
Participants with child-pugh (CP) scores of 5 or 6 received a starting dose of 12 milligram (mg) (three 4 mg tablets) lenvatinib orally once daily (QD) in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.
|
Phase 1: Group 1: Lenvatinib: 16 mg
Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 2: Lenvatinib: 12 mg
Participants with CP scores of 5 or 6 received recommended dose (RD) of 12 mg (three 4 mg tablets) lenvatinib established from group 1, in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|---|
|
Phase 2
Adverse Event
|
0
|
0
|
0
|
0
|
6
|
|
Phase 2
Need more reduction of dose
|
0
|
0
|
0
|
0
|
2
|
|
Phase 2
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
|
Phase 2
14 days washout for recovery due to AE
|
0
|
0
|
0
|
0
|
4
|
Baseline Characteristics
Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)
Baseline characteristics by cohort
| Measure |
Phase 1: Group 1: Lenvatinib: 12 mg
n=6 Participants
Participants with CP scores of 5 or 6 received a starting dose of 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.
|
Phase 1: Group 1: Lenvatinib: 16 mg
n=3 Participants
Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 Participants
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 2: Lenvatinib: 12 mg
n=46 Participants
Participants with CP scores of 5 or 6 received RD of 12 mg (three 4 mg tablets) lenvatinib established from group 1, in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Customized
>=37 years and <=80 years
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
46 Participants
n=31 Participants
|
66 Participants
n=30 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
13 Participants
n=31 Participants
|
16 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
33 Participants
n=31 Participants
|
50 Participants
n=30 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
46 Participants
n=31 Participants
|
66 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days (Cycle1)Population: Safety analysis set (SAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline safety evaluation.
The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (\>) 10.0\*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria \>3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=9 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
n=11 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
|
12 milligram (mg)
|
8 milligram (mg)
|
—
|
—
|
PRIMARY outcome
Timeframe: From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)Population: Per protocol set (PPS) included all participants in full analysis set (FAS), who showed greater than or equal to (\>=) 75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.
TTP was defined as the time from the date of registration to the date when progressive disease (PD) was first confirmed. PD was evaluated according to modified response evaluation criteria in solid tumors (mRECIST) by an independent imaging review. PD was defined as at least a 20 percent (%) increase in the sum of long diameter (LD) of target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 millimeter (mm) (including new lesions).
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=41 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 2: Time to Progression (TTP) by Independent Review Assessment
|
7.40 months
Interval 5.5 to 9.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Every 8 weeks (approximately up to 18.4 months)Population: Efficacy analysis set (EAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
BOR was performed using RECIST1.1 and was measured as complete response (CR) defined as when an overall response of CR was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of CR was confirmed and the BOR established as CR was regarded as the "CR confirmed date), partial response (PR) defined as when the overall response of PR or better (CR or PR) was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of PR was confirmed and the BOR established as PR will be regarded as the "PR confirmed date), PD defined as when the BOR was neither CR, PR, or stable disease (SD), and the overall response was PD, SD defined as when the BOR obtained was neither CR nor PR, but no PD from the initial administration to the end of Cycle 2 and the overall response of SD or better occurred at least once and not evaluable (NE) was when the overall response was NE in all cases.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=6 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
n=3 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 Participants
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Partial Response
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Stable Disease
|
2 Participants
|
2 Participants
|
4 Participants
|
2 Participants
|
|
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Progressive Disease
|
2 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Not Evaluable
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)Population: EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
ORR was defined as the percentage of participants who achieved a tumor response measured by RECIST 1.1 of CR defined as disappearance of all target lesions (a short diameter is less than (\<)10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=6 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
n=3 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 Participants
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 1: Objective Response Rate (ORR) by Investigator Assessment
|
16.7 percentage of participants
|
33.3 percentage of participants
|
16.7 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Week 16Population: EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
DCR was measured by RECIST 1.1 and defined as CR which was defined as disappearance of all target lesions (a short diameter was \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=6 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
n=3 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 Participants
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 Participants
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 1: Disease Control Rate (DCR) by Investigator Assessment
|
50 percentage of participants
|
100 percentage of participants
|
83.3 percentage of participants
|
40.0 percentage of participants
|
SECONDARY outcome
Timeframe: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.
PFS was defined as the time from the date of registration until the date when PD was first confirmed or death (whichever occurred first) as determined by mRECIST and PD was defined as at least a 20% increase in the sum of long diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=41 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
|
7.40 months
Interval 5.5 to 9.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.
ORR was defined as the percentage of participants who achieved a tumor response measured by mRECIST of CR defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=41 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
|
41.5 percentage of participants
Interval 26.3 to 57.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 8 and 16Population: PPS included all participants in the FAS showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.
DCR was measured by mRECIST and defined as CR which was defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=41 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
Week 8
|
87.8 percentage of participant
Interval 73.8 to 95.9
|
—
|
—
|
—
|
|
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
Week 16
|
78.0 percentage of participant
Interval 62.4 to 89.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From day of registration to the day of death (approximately 6.1 years)Population: PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.
OS was defined as the time from the date of registration until the date of death.
Outcome measures
| Measure |
Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)
n=41 Participants
Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|
|
Phase 2: Overall Survival (OS)
|
18.30 months
Interval 12.7 to 25.1
|
—
|
—
|
—
|
Adverse Events
Phase 1: Group 1: Lenvatinib: 12 mg
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase 1: Group 1: Lenvatinib: 16 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1: Group 2: Lenvatinib: 8 mg
Serious events: 3 serious events
Other events: 6 other events
Deaths: 1 deaths
Phase 1: Group 2: Lenvatinib: 12 mg
Serious events: 3 serious events
Other events: 5 other events
Deaths: 1 deaths
Phase 2: Lenvatinib: 12 mg
Serious events: 22 serious events
Other events: 46 other events
Deaths: 32 deaths
Serious adverse events
| Measure |
Phase 1: Group 1: Lenvatinib: 12 mg
n=6 participants at risk
Participants with child CP scores of 5 or 6 received a starting dose of 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.
|
Phase 1: Group 1: Lenvatinib: 16 mg
n=3 participants at risk
Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 participants at risk
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 participants at risk
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 2: Lenvatinib: 12 mg
n=46 participants at risk
Participants with CP scores of 5 or 6 received lenvatinib RD of 12 mg (three 4 mg tablets) established from group 1 in the dose escalation component (Phase1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Biliary tract infection
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Cardiac tamponade
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Oedema peripheral
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Septic shock
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour rupture
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
Other adverse events
| Measure |
Phase 1: Group 1: Lenvatinib: 12 mg
n=6 participants at risk
Participants with child CP scores of 5 or 6 received a starting dose of 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.
|
Phase 1: Group 1: Lenvatinib: 16 mg
n=3 participants at risk
Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 8 mg
n=6 participants at risk
Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 1: Group 2: Lenvatinib: 12 mg
n=5 participants at risk
Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.
|
Phase 2: Lenvatinib: 12 mg
n=46 participants at risk
Participants with CP scores of 5 or 6 received lenvatinib RD of 12 mg (three 4 mg tablets) established from group 1 in the dose escalation component (Phase1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.
|
|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
34.8%
16/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
15.2%
7/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
4/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
28.3%
13/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Supraventricular extrasystoles
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
21.7%
10/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Eye disorders
Vitreous detachment
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Eye disorders
Eye pruritus
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Eye disorders
Vision blurred
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Congenital, familial and genetic disorders
Hydrocele
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Abdominal distension
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Anal pruritus
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Cheilitis
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
41.3%
19/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
6/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
6/6 • From start of study drug administration until approximately up to 6.1 years
|
60.0%
3/5 • From start of study drug administration until approximately up to 6.1 years
|
43.5%
20/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Faeces discoloured
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gingival inflammation
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
80.0%
4/5 • From start of study drug administration until approximately up to 6.1 years
|
34.8%
16/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Stomatitis
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
23.9%
11/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
60.0%
3/5 • From start of study drug administration until approximately up to 6.1 years
|
23.9%
11/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Fatigue
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
5/5 • From start of study drug administration until approximately up to 6.1 years
|
54.3%
25/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Mucosal inflammation
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Oedema peripheral
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
2/3 • From start of study drug administration until approximately up to 6.1 years
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
34.8%
16/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Pyrexia
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
21.7%
10/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
4/6 • From start of study drug administration until approximately up to 6.1 years
|
80.0%
4/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Biliary tract infection
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Gingivitis
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Infection
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
28.3%
13/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Pharyngitis
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Anal abscess
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Empyema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Hordeolum
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Influenza
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Lung infection
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Omphalitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Periodontitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Proctitis infectious
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Rhinitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Hand fracture
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Tooth injury
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Alanine aminotransferase increased
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
60.0%
3/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Aspartate aminotransferase increased
|
66.7%
4/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
60.0%
3/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood alkaline phosphatase increased
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood albumin decreased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood bilirubin increased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood lactate dehydrogenase increased
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood thyroid stimulating hormone decreased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood thyroid stimulating hormone increased
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
26.1%
12/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood urine present
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
19.6%
9/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
C-reactive protein increased
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Haemoglobin decreased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
International normalised ratio increased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Thyroxine free decreased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Thyroxine free increased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Tri-iodothyronine free decreased
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Tri-iodothyronine free increased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Weight decreased
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
30.4%
14/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
White blood cell count decreased
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood calcium decreased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood potassium increased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Blood urea increased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Occult blood
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
17.4%
8/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
100.0%
6/6 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
2/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
5/5 • From start of study drug administration until approximately up to 6.1 years
|
60.9%
28/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
13.0%
6/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypochloraemia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
2/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hyperammonaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
17.4%
8/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
23.9%
11/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
19.6%
9/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
2/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
21.7%
10/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Proteinuria
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
66.7%
2/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
58.7%
27/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
17.4%
8/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
60.0%
3/5 • From start of study drug administration until approximately up to 6.1 years
|
37.0%
17/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
15.2%
7/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
65.2%
30/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
30.4%
14/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Vascular disorders
Hypertension
|
83.3%
5/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
80.0%
4/5 • From start of study drug administration until approximately up to 6.1 years
|
76.1%
35/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
1/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
3/6 • From start of study drug administration until approximately up to 6.1 years
|
100.0%
3/3 • From start of study drug administration until approximately up to 6.1 years
|
33.3%
2/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
23.9%
11/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
8.7%
4/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Vascular disorders
Phlebitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Vascular disorders
Hyperaemia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gastritis atrophic
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Tooth disorder
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
10.9%
5/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Disuse syndrome
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Face oedema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
20.0%
1/5 • From start of study drug administration until approximately up to 6.1 years
|
6.5%
3/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
General physical health deterioration
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
40.0%
2/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Localised oedema
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Malaise
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Puncture site haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
General disorders
Puncture site pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Tension headache
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Tremor
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Psychiatric disorders
Depression
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Incontinence
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Renal and urinary disorders
Urethral haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
16.7%
1/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Endocrine disorders
Thyroiditis
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
4.3%
2/46 • From start of study drug administration until approximately up to 6.1 years
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/3 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/6 • From start of study drug administration until approximately up to 6.1 years
|
0.00%
0/5 • From start of study drug administration until approximately up to 6.1 years
|
2.2%
1/46 • From start of study drug administration until approximately up to 6.1 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place