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Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)

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ClinicalTrials.gov Identifier: NCT00946153
Recruitment Status : Completed
First Posted : July 24, 2009
Results First Posted : February 1, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Intervention Drug: Lenvatinib
Enrollment 66
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg
Hide Arm/Group Description 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. 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. 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. 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. 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.
Period Title: Phase 1
Started 6 3 6 5 0
Completed 6 3 6 5 0
Not Completed 0 0 0 0 0
Period Title: Phase 2
Started 0 0 0 0 46
Completed 0 0 0 0 33
Not Completed 0 0 0 0 13
Reason Not Completed
Adverse Event             0             0             0             0             6
Need more reduction of dose             0             0             0             0             2
Physician Decision             0             0             0             0             1
14 days washout for recovery due to AE             0             0             0             0             4
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg Total
Hide Arm/Group Description 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. 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. 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 6 3 6 5 46 66
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline efficacy evaluation.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
>=37 years and <=80 years Number Analyzed 6 participants 3 participants 6 participants 5 participants 46 participants 66 participants
6
 100.0%
3
 100.0%
6
 100.0%
5
 100.0%
46
 100.0%
66
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 6 participants 5 participants 46 participants 66 participants
Female 1 2 0 0 13 16
Male 5 1 6 5 33 50
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 6 participants 5 participants 46 participants 66 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
6
 100.0%
3
 100.0%
6
 100.0%
5
 100.0%
46
 100.0%
66
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
Hide Description 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.
Time Frame Up to 28 days (Cycle1)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline safety evaluation.
Arm/Group Title Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6) Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 11
Measure Type: Number
Unit of Measure: milligram (mg)
12 8
2.Primary Outcome
Title Phase 2: Time to Progression (TTP) by Independent Review Assessment
Hide Description 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).
Time Frame From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 : Lenvatinib :12 mg
Hide Arm/Group Description:
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 (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.
Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
7.40
(5.50 to 9.40)
3.Secondary Outcome
Title Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Hide Description 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.
Time Frame Every 8 weeks (approximately up to 18.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis set (EAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 6 3 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Partial Response
1
  16.7%
1
  33.3%
1
  16.7%
0
   0.0%
Stable Disease
2
  33.3%
2
  66.7%
4
  66.7%
2
  40.0%
Progressive Disease
2
  33.3%
0
   0.0%
1
  16.7%
3
  60.0%
Not Evaluable
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Phase 1: Objective Response Rate (ORR) by Investigator Assessment
Hide Description 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.
Time Frame From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Hide Outcome Measure Data
Hide Analysis Population Description
EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 6 3 6 5
Measure Type: Number
Unit of Measure: percentage of participants
16.7 33.3 16.7 0
5.Secondary Outcome
Title Phase 1: Disease Control Rate (DCR) by Investigator Assessment
Hide Description 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.
Time Frame Up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 6 3 6 5
Measure Type: Number
Unit of Measure: percentage of participants
50 100 83.3 40.0
6.Secondary Outcome
Title Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
Hide Description 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.
Time Frame From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 : Lenvatinib :12 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
7.40
(5.50 to 9.40)
7.Secondary Outcome
Title Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
Hide Description 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.
Time Frame From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 : Lenvatinib :12 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.5
(26.3 to 57.9)
8.Secondary Outcome
Title Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
Hide Description 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.
Time Frame Weeks 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 : Lenvatinib :12 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participant
Week 8
87.8
(73.8 to 95.9)
Week 16
78.0
(62.4 to 89.4)
9.Secondary Outcome
Title Phase 2: Overall Survival (OS)
Hide Description OS was defined as the time from the date of registration until the date of death.
Time Frame From day of registration to the day of death (approximately 6.1 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 : Lenvatinib :12 mg
Hide Arm/Group Description:
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 (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.
Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
18.30
(12.70 to 25.10)
Time Frame From start of study drug administration until approximately up to 6.1 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg
Hide Arm/Group Description 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. 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. 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. 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. 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.
All-Cause Mortality
Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/3 (0.00%)   1/6 (16.67%)   1/5 (20.00%)   32/46 (69.57%) 
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)   2/3 (66.67%)   3/6 (50.00%)   3/5 (60.00%)   22/46 (47.83%) 
Cardiac disorders           
Acute coronary syndrome  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Angina pectoris  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Cardiac tamponade  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastrointestinal disorders           
Haematemesis  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Gastritis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Nausea  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Oesophageal varices haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Vomiting  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
General disorders           
Oedema peripheral  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Hepatobiliary disorders           
Hepatic failure  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Hyperbilirubinaemia  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Cholecystitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Cholecystitis acute  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Jaundice cholestatic  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Portal vein thrombosis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Infections and infestations           
Biliary tract infection  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Pneumonia  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Septic shock  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Metabolism and nutrition disorders           
Hypoalbuminaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hypoglycaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Lymphoma  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Tumour rupture  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Tumour haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  0/46 (0.00%) 
Nervous system disorders           
Hepatic encephalopathy  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/5 (20.00%)  5/46 (10.87%) 
Syncope  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Renal and urinary disorders           
Proteinuria  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Renal impairment  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Respiratory, thoracic and mediastinal disorders           
Haemoptysis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Respiratory failure  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1: Group 1: Lenvatinib: 12 mg Phase 1: Group 1: Lenvatinib: 16 mg Phase 1: Group 2: Lenvatinib: 8 mg Phase 1: Group 2: Lenvatinib: 12 mg Phase 2: Lenvatinib: 12 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   5/5 (100.00%)   46/46 (100.00%) 
Blood and lymphatic system disorders           
Anaemia  1  0/6 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Lymphopenia  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Thrombocytopenia  1  2/6 (33.33%)  1/3 (33.33%)  1/6 (16.67%)  2/5 (40.00%)  16/46 (34.78%) 
Leukopenia  1  0/6 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  1/5 (20.00%)  7/46 (15.22%) 
Disseminated intravascular coagulation  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Neutropenia  1  0/6 (0.00%)  0/3 (0.00%)  4/6 (66.67%)  1/5 (20.00%)  13/46 (28.26%) 
Cardiac disorders           
Supraventricular extrasystoles  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Cardiac failure  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Pericarditis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Arrhythmia  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Atrioventricular block  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Congenital, familial and genetic disorders           
Hydrocele  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Ear and labyrinth disorders           
Tinnitus  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Ear discomfort  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Endocrine disorders           
Hypothyroidism  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  10/46 (21.74%) 
Hyperthyroidism  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Thyroiditis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Eye disorders           
Vitreous detachment  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Conjunctival haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Eye pruritus  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Vision blurred  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Eyelid oedema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastrointestinal disorders           
Abdominal distension  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  4/46 (8.70%) 
Abdominal pain  1  2/6 (33.33%)  1/3 (33.33%)  3/6 (50.00%)  2/5 (40.00%)  5/46 (10.87%) 
Anal pruritus  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Cheilitis  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Constipation  1  2/6 (33.33%)  3/3 (100.00%)  0/6 (0.00%)  0/5 (0.00%)  19/46 (41.30%) 
Diarrhoea  1  6/6 (100.00%)  3/3 (100.00%)  6/6 (100.00%)  3/5 (60.00%)  20/46 (43.48%) 
Faeces discoloured  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Gingival inflammation  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Nausea  1  2/6 (33.33%)  3/3 (100.00%)  3/6 (50.00%)  4/5 (80.00%)  16/46 (34.78%) 
Stomatitis  1  3/6 (50.00%)  0/3 (0.00%)  2/6 (33.33%)  1/5 (20.00%)  11/46 (23.91%) 
Abdominal discomfort  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Epigastric discomfort  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  2/46 (4.35%) 
Gastritis  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/46 (2.17%) 
Abdominal pain lower  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Abdominal pain upper  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Ascites  1  0/6 (0.00%)  0/3 (0.00%)  3/6 (50.00%)  3/5 (60.00%)  11/46 (23.91%) 
Hypoaesthesia oral  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Vomiting  1  3/6 (50.00%)  3/3 (100.00%)  2/6 (33.33%)  2/5 (40.00%)  11/46 (23.91%) 
Dental caries  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Dyspepsia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  5/46 (10.87%) 
Enteritis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Enterocolitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Gastric ulcer  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastritis atrophic  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastrooesophageal reflux disease  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gingival bleeding  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Glossitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Haemorrhoidal haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Haemorrhoids  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Periodontal disease  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Tooth disorder  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Varices oesophageal  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  5/46 (10.87%) 
General disorders           
Fatigue  1  5/6 (83.33%)  3/3 (100.00%)  5/6 (83.33%)  5/5 (100.00%)  25/46 (54.35%) 
Mucosal inflammation  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/46 (2.17%) 
Oedema peripheral  1  0/6 (0.00%)  2/3 (66.67%)  5/6 (83.33%)  1/5 (20.00%)  16/46 (34.78%) 
Pyrexia  1  2/6 (33.33%)  1/3 (33.33%)  3/6 (50.00%)  1/5 (20.00%)  10/46 (21.74%) 
Disuse syndrome  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Face oedema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  3/46 (6.52%) 
General physical health deterioration  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/5 (40.00%)  1/46 (2.17%) 
Influenza like illness  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Localised oedema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Malaise  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Puncture site haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Puncture site pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hepatobiliary disorders           
Hepatic function abnormal  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Hyperbilirubinaemia  1  1/6 (16.67%)  1/3 (33.33%)  4/6 (66.67%)  4/5 (80.00%)  3/46 (6.52%) 
Cholelithiasis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Portal vein thrombosis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Immune system disorders           
Hypersensitivity  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Infections and infestations           
Biliary tract infection  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Gingivitis  1  2/6 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Infection  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Nasopharyngitis  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  13/46 (28.26%) 
Pharyngitis  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Pyelonephritis  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Subcutaneous abscess  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Bronchitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Anal abscess  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Empyema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastroenteritis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Gastroenteritis viral  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hordeolum  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Influenza  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Lung infection  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Omphalitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Periodontitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Proctitis infectious  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Rhinitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Sinusitis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Injury, poisoning and procedural complications           
Hand fracture  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Post procedural haemorrhage  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Arthropod sting  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Fall  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/46 (2.17%) 
Fracture  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Incisional hernia  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Ligament sprain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Rib fracture  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Subcutaneous haematoma  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Tooth injury  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Contusion  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Investigations           
Alanine aminotransferase increased  1  3/6 (50.00%)  0/3 (0.00%)  0/6 (0.00%)  3/5 (60.00%)  2/46 (4.35%) 
Aspartate aminotransferase increased  1  4/6 (66.67%)  0/3 (0.00%)  0/6 (0.00%)  3/5 (60.00%)  5/46 (10.87%) 
Blood alkaline phosphatase increased  1  3/6 (50.00%)  0/3 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  2/46 (4.35%) 
Blood albumin decreased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Blood bilirubin increased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Blood lactate dehydrogenase increased  1  3/6 (50.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Blood thyroid stimulating hormone decreased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Blood thyroid stimulating hormone increased  1  5/6 (83.33%)  1/3 (33.33%)  2/6 (33.33%)  1/5 (20.00%)  12/46 (26.09%) 
Blood urine present  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  9/46 (19.57%) 
C-reactive protein increased  1  2/6 (33.33%)  1/3 (33.33%)  1/6 (16.67%)  1/5 (20.00%)  3/46 (6.52%) 
Gamma-glutamyltransferase increased  1  3/6 (50.00%)  0/3 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  4/46 (8.70%) 
Haemoglobin decreased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
International normalised ratio increased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Neutrophil count decreased  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  5/46 (10.87%) 
Thyroxine free decreased  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Thyroxine free increased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Tri-iodothyronine free decreased  1  2/6 (33.33%)  1/3 (33.33%)  0/6 (0.00%)  1/5 (20.00%)  0/46 (0.00%) 
Tri-iodothyronine free increased  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Weight decreased  1  3/6 (50.00%)  1/3 (33.33%)  3/6 (50.00%)  2/5 (40.00%)  14/46 (30.43%) 
White blood cell count decreased  1  1/6 (16.67%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  5/46 (10.87%) 
Blood creatinine increased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  2/46 (4.35%) 
Blood calcium decreased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Blood potassium increased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Blood urea increased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Electrocardiogram QT prolonged  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Occult blood  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Platelet count decreased  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  8/46 (17.39%) 
Metabolism and nutrition disorders           
Decreased appetite  1  6/6 (100.00%)  2/3 (66.67%)  3/6 (50.00%)  5/5 (100.00%)  28/46 (60.87%) 
Dehydration  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  4/46 (8.70%) 
Hypoalbuminaemia  1  3/6 (50.00%)  1/3 (33.33%)  1/6 (16.67%)  1/5 (20.00%)  6/46 (13.04%) 
Hypochloraemia  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Hyponatraemia  1  1/6 (16.67%)  2/3 (66.67%)  1/6 (16.67%)  1/5 (20.00%)  2/46 (4.35%) 
Hyperammonaemia  1  0/6 (0.00%)  0/3 (0.00%)  3/6 (50.00%)  2/5 (40.00%)  3/46 (6.52%) 
Hypercholesterolaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hyperkalaemia  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/46 (2.17%) 
Hyperuricaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hypocalcaemia  1  0/6 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/5 (0.00%)  1/46 (2.17%) 
Hypoglycaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Hypokalaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Malnutrition  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  8/46 (17.39%) 
Back pain  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  11/46 (23.91%) 
Muscle spasms  1  1/6 (16.67%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Musculoskeletal chest pain  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Musculoskeletal pain  1  1/6 (16.67%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  5/46 (10.87%) 
Musculoskeletal stiffness  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Arthritis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Flank pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Myalgia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Neck pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Pain in extremity  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  4/46 (8.70%) 
Pain in jaw  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Bone pain  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  2/46 (4.35%) 
Tumour associated fever  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Nervous system disorders           
Dysgeusia  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Headache  1  2/6 (33.33%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  9/46 (19.57%) 
Hepatic encephalopathy  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Dizziness  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Peripheral sensory neuropathy  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Somnolence  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Tension headache  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Tremor  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hypoaesthesia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Psychiatric disorders           
Confusional state  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Insomnia  1  1/6 (16.67%)  2/3 (66.67%)  0/6 (0.00%)  1/5 (20.00%)  10/46 (21.74%) 
Anxiety  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Depression  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Hallucination  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Renal and urinary disorders           
Proteinuria  1  2/6 (33.33%)  2/3 (66.67%)  1/6 (16.67%)  2/5 (40.00%)  27/46 (58.70%) 
Renal impairment  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  2/46 (4.35%) 
Haematuria  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Incontinence  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Pollakiuria  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Urethral haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Reproductive system and breast disorders           
Genital haemorrhage  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  0/6 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  8/46 (17.39%) 
Dysphonia  1  2/6 (33.33%)  1/3 (33.33%)  2/6 (33.33%)  3/5 (60.00%)  17/46 (36.96%) 
Epistaxis  1  1/6 (16.67%)  1/3 (33.33%)  2/6 (33.33%)  0/5 (0.00%)  7/46 (15.22%) 
Hypoxia  1  0/6 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/5 (0.00%)  0/46 (0.00%) 
Oropharyngeal pain  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/46 (4.35%) 
Hiccups  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/46 (2.17%) 
Pleural effusion  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  4/46 (8.70%) 
Atelectasis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Haemoptysis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Productive cough  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Rhinorrhoea  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Upper respiratory tract inflammation  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Dyspnoea  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  1/6 (16.67%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  3/46 (6.52%) 
Palmar-plantar erythrodysaesthesia syndrome  1  5/6 (83.33%)  3/3 (100.00%)  3/6 (50.00%)  2/5 (40.00%)  30/46 (65.22%) 
Pruritus  1  1/6 (16.67%)  1/3 (33.33%)  1/6 (16.67%)  0/5 (0.00%)  4/46 (8.70%) 
Rash  1  3/6 (50.00%)  0/3 (0.00%)  2/6 (33.33%)  1/5 (20.00%)  14/46 (30.43%) 
Decubitus ulcer  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/46 (2.17%) 
Dermatitis acneiform  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Erythema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  2/46 (4.35%) 
Nail disorder  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/46 (2.17%) 
Acne  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Dermal cyst  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Dermatitis exfoliative  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Dry skin  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  4/46 (8.70%) 
Eczema  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Haemorrhage subcutaneous  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hyperkeratosis  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  3/46 (6.52%) 
Petechiae  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Purpura  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/46 (4.35%) 
Vascular disorders           
Hypertension  1  5/6 (83.33%)  3/3 (100.00%)  3/6 (50.00%)  4/5 (80.00%)  35/46 (76.09%) 
Phlebitis  1  0/6 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/46 (0.00%) 
Hyperaemia  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
Hypotension  1  0/6 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Eisai Medical Services
Organization: Eisai, Inc.
Phone: 1-888-422-4743
Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier: NCT00946153     History of Changes
Other Study ID Numbers: E7080-J081-202
First Submitted: July 23, 2009
First Posted: July 24, 2009
Results First Submitted: August 27, 2018
Results First Posted: February 1, 2019
Last Update Posted: February 1, 2019