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Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy (METIV-HCC)

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ClinicalTrials.gov Identifier: NCT01755767
Recruitment Status : Completed
First Posted : December 24, 2012
Results First Posted : July 15, 2020
Last Update Posted : April 6, 2021
Sponsor:
Collaborator:
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Information provided by (Responsible Party):
Daiichi Sankyo

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Interventions Drug: Tivantinib
Drug: Placebo
Enrollment 383
Recruitment Details A total of 383 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment. One participant in the tivantinib 120 mg BID cohort was randomized but did not receive treatment.
Pre-assignment Details Eligible participants were randomly assigned on a 2:1 basis to either tivantinib or placebo. Initially, the tivantinib dosage of 240 mg was selected on the basis of efficacy and tolerability established in Phase 1 and Phase 2 studies.
Arm/Group Title Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description Participants who received tivantinib 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg. Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group). Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Period Title: Overall Study
Started 28 15 226 114
Completed 0 0 0 0
Not Completed 28 15 226 114
Reason Not Completed
Progressive Disease             8             7             91             43
Clinical Disease Progression             4             2             29             20
Radiographic Disease Progression             9             4             44             27
Adverse Event             6             0             28             11
Death             1             2             15             4
Subject Decision             0             0             10             3
Withdrawal by Subject             0             0             2             1
Other             0             0             2             3
Ongoing Treatment as of 06 Jan 2017             0             0             5             2
Arm/Group Title Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort Total
Hide Arm/Group Description Participants who received tivantinib 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg. Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group). Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. Total of all reporting groups
Overall Number of Baseline Participants 28 15 225 114 382
Hide Baseline Analysis Population Description
Demographic and baseline characteristics are reported in the Safety Analysis Set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 15 participants 225 participants 114 participants 382 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
11
  39.3%
5
  33.3%
98
  43.6%
50
  43.9%
164
  42.9%
>=65 years
17
  60.7%
10
  66.7%
127
  56.4%
64
  56.1%
218
  57.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants 15 participants 225 participants 114 participants 382 participants
66.6  (9.3) 64.9  (7.4) 65.6  (10.2) 64.7  (10.2) 64.8  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 15 participants 225 participants 114 participants 382 participants
Female
4
  14.3%
0
   0.0%
27
  12.0%
7
   6.1%
38
   9.9%
Male
24
  85.7%
15
 100.0%
198
  88.0%
107
  93.9%
344
  90.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 15 participants 225 participants 114 participants 382 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
2
   0.9%
0
   0.0%
2
   0.5%
Asian
1
   3.6%
0
   0.0%
8
   3.6%
7
   6.1%
16
   4.2%
Native Hawaiian or Other Pacific Islander
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%
11
   4.9%
1
   0.9%
12
   3.1%
White
27
  96.4%
15
 100.0%
161
  71.6%
86
  75.4%
289
  75.7%
More than one race
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%
43
  19.1%
20
  17.5%
63
  16.5%
1.Primary Outcome
Title Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Hide Description Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Time Frame within 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
Overall survival was assessed in the Intent-to-Treat Analysis Set.
Arm/Group Title Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description:
Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Overall Number of Participants Analyzed 226 114
Median (95% Confidence Interval)
Unit of Measure: months
8.4
(6.8 to 10.0)
9.1
(7.3 to 10.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivantinib 120 mg BID Cohort
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8006
Comments [Not Specified]
Method Log Rank
Comments Stratified log rank between treatment arms adjusted for stratification factors: vascular invasion, extra-hepatic spread, and alpha fetoprotein level.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tivantinib 120 mg BID Cohort, Placebo Matching 120 mg BID Cohort
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8061
Comments [Not Specified]
Method Regression, Cox
Comments Stratified Cox Regression between treatment arms adjusted for factors: vascular invasion, extra-hepatic spread, and alpha fetoprotein level.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9682
Confidence Interval (2-Sided) 95%
0.7483 to 1.2529
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Hide Description Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
Time Frame within 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
Overall survival was assessed in the Intent-to-Treat Analysis Set.
Arm/Group Title Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description:
Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Overall Number of Participants Analyzed 226 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants still alive
Overall survival at 3 months
86.6
(81.4 to 90.5)
85.9
(78.0 to 91.1)
Overall survival at 6 months
61.2
(54.5 to 67.2)
70.8
(61.5 to 78.3)
Overall survival at 9 months
46.9
(40.2 to 53.3)
50.5
(40.9 to 59.2)
Overall survival at 12 months
36.6
(30.3 to 42.9)
38.0
(29.1 to 46.9)
Overall survival at 18 months
25.1
(19.4 to 31.2)
21.9
(14.3 to 30.5)
Overall survival at 24 months
16.2
(11.0 to 22.3)
12.2
(5.9 to 20.8)
3.Secondary Outcome
Title Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population)
Hide Description Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause. The rate of PFS (percentage of participants still alive without disease progression) was determined only in the tivantinib 120 mg BID cohort.
Time Frame within 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
PFS was assessed in the Intent-to-Treat Analysis Set.
Arm/Group Title Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description:
Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Overall Number of Participants Analyzed 226 114
Median (95% Confidence Interval)
Unit of Measure: months
2.1
(1.9 to 3.0)
2.0
(1.9 to 3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivantinib 120 mg BID Cohort, Placebo Matching 120 mg BID Cohort
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7509
Comments [Not Specified]
Method Log Rank
Comments Stratified log rank between treatment arms adjusted for stratification factors: vascular invasion, extra-hepatic spread, and alpha fetoprotein level.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tivantinib 120 mg BID Cohort, Placebo Matching 120 mg BID Cohort
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7160
Comments [Not Specified]
Method Regression, Cox
Comments Stratified Cox regression between treatment arms adjusted for factors: vascular invasion, extra-hepatic spread, and alpha fetoprotein level.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9557
Confidence Interval (2-Sided) 95%
0.7487 to 1.2200
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Hide Description Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.
Time Frame Baseline to 30 days after last dose, up to approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
TEAEs were assessed in the Safety Analysis Set.
Arm/Group Title Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description:
Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Overall Number of Participants Analyzed 225 114
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
214
  95.1%
108
  94.7%
Gastrointestinal Disorders
159
  70.7%
84
  73.7%
General Disorders & Administration Site Conditions
146
  64.9%
75
  65.8%
Musculoskeletal and Connective Tissue Disorders
75
  33.3%
34
  29.8%
Respiratory, Thoracic, and Mediastinal Disorders
70
  31.1%
32
  28.1%
Metabolism and Nutrition Disorders
65
  28.9%
30
  26.3%
Blood and Lymphatic System Disorders
64
  28.4%
27
  23.7%
Nervous System Disorders
60
  26.7%
27
  23.7%
Infections and Infestations
58
  25.8%
33
  28.9%
Skin and Subcutaneous Tissue Disorders
57
  25.3%
38
  33.3%
Investigations
55
  24.4%
36
  31.6%
Cardiac Disorders
52
  23.1%
13
  11.4%
5.Secondary Outcome
Title Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Hide Description Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.
Time Frame Baseline to 30 days after last dose, up to approximately 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
TEAEs were assessed in the Safety Analysis Set.
Arm/Group Title Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort
Hide Arm/Group Description:
Participants who received tivantinib 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg (amended dosing group; primary analysis group).
Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
Overall Number of Participants Analyzed 28 15
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
28
 100.0%
14
  93.3%
Blood and Lymphatic System Disorders
20
  71.4%
4
  26.7%
Gastrointestinal Disorders
20
  71.4%
12
  80.0%
General Disorders & Administration Site Conditions
19
  67.9%
9
  60.0%
Investigations
11
  39.3%
8
  53.3%
Respiratory, Thoracic, and Mediastinal Disorders
8
  28.6%
4
  26.7%
Infections and Infestations
7
  25.0%
3
  20.0%
Skin and Subcutaneous Tissue Disorders
7
  25.0%
3
  20.0%
Cardiac Disorders
7
  25.0%
0
   0.0%
Metabolism and Nutrition Disorders
6
  21.4%
5
  33.3%
Time Frame Adverse events (AEs) were collected from baseline to 30 days after the last dose up to approximately 4 years.
Adverse Event Reporting Description Treatment-emergent AEs (TEAEs) were defined as those AEs that occurred, having been absent before the study, or worsen in severity after the initiation of study treatment administration and started no later than 30 days after the end of treatment.
 
Arm/Group Title Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Hide Arm/Group Description Participants who received tivantinib 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg. Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food. Participants who received tivantinib 120 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group). Participants who received matching placebo tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food.
All-Cause Mortality
Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/28 (100.00%)   14/15 (93.33%)   180/225 (80.00%)   94/114 (82.46%) 
Hide Serious Adverse Events
Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/28 (60.71%)   10/15 (66.67%)   103/225 (45.78%)   51/114 (44.74%) 
Blood and lymphatic system disorders         
Anaemia † 1  0/28 (0.00%)  0/15 (0.00%)  4/225 (1.78%)  3/114 (2.63%) 
Febrile neutropenia † 1  1/28 (3.57%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Leukopenia † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Neutropenia † 1  1/28 (3.57%)  0/15 (0.00%)  3/225 (1.33%)  0/114 (0.00%) 
Thrombocytopenia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pancytopenia † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Cardiac disorders         
Acute coronary syndrome † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Acute myocardial infarction † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Atrial fibrillation † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Atrioventricular block complete † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Bradycardia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Cardiac arrest † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Cardiac failure † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Myocardial infarction † 1  2/28 (7.14%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Cardiac failure congestive † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Gastrointestinal disorders         
Abdominal hernia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Abdominal pain † 1  1/28 (3.57%)  0/15 (0.00%)  2/225 (0.89%)  4/114 (3.51%) 
Ascites † 1  0/28 (0.00%)  2/15 (13.33%)  7/225 (3.11%)  3/114 (2.63%) 
Constipation † 1  0/28 (0.00%)  1/15 (6.67%)  1/225 (0.44%)  0/114 (0.00%) 
Diarrhoea † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Duodenal ulcer † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Duodenal ulcer haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Gastric haemorrhage † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  2/114 (1.75%) 
Gastrointestinal haemorrhage † 1  1/28 (3.57%)  0/15 (0.00%)  8/225 (3.56%)  2/114 (1.75%) 
Haematemesis † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Haemorrhoidal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Intra-abdominal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Melaena † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Oesophageal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Oesophageal varices haemorrhage † 1  1/28 (3.57%)  2/15 (13.33%)  6/225 (2.67%)  3/114 (2.63%) 
Peritoneal haemorrhage † 1  0/28 (0.00%)  1/15 (6.67%)  2/225 (0.89%)  0/114 (0.00%) 
Rectal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Retroperitoneal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Subileus † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Upper gastrointestinal haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  3/225 (1.33%)  0/114 (0.00%) 
Varices oesophageal † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Vomiting † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Haemorrhagic ascites † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Ileus † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
General disorders         
Asthenia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Chest pain † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Device malfunction † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Disease progression † 1  2/28 (7.14%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Fatigue † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  2/114 (1.75%) 
General physical health deterioration † 1  0/28 (0.00%)  0/15 (0.00%)  11/225 (4.89%)  2/114 (1.75%) 
Implant site haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pyrexia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  2/114 (1.75%) 
Device dislocation † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Multi-organ failure † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Oedema peripheral † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Hepatobiliary disorders         
Acute hepatic failure † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Cholangitis † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  2/114 (1.75%) 
Cholelithiasis † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Cholestasis † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Hepatic cirrhosis † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Hepatic failure † 1  1/28 (3.57%)  1/15 (6.67%)  2/225 (0.89%)  0/114 (0.00%) 
Hepatorenal failure † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Hepatorenal syndrome † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Hepatotoxicity † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Hyperbilirubinaemia † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Jaundice † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Jaundice cholestatic † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  2/114 (1.75%) 
Portal vein thrombosis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Liver injury † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Infections and infestations         
Cellulitis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Cellulitis orbital † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Gastroenteritis † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Herpes zoster † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Lung infection † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Peritonitis bacterial † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pneumonia † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Pulmonary sepsis † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Respiratory tract infection † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Sepsis † 1  1/28 (3.57%)  0/15 (0.00%)  6/225 (2.67%)  0/114 (0.00%) 
Septic shock † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Staphylococcal sepsis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Upper respiratory tract infection † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Urinary tract infection † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Wound infection † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pseudomonal sepsis † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Injury, poisoning and procedural complications         
Adrenal gland injury † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Fall † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Foot fracture † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Humerus fracture † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Periprosthetic fracture † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Post procedural haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Procedural pain † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Wound † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Investigations         
Alanine aminotransferase increased † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Aspartate aminotransferase increased † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Blood bilirubin increased † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Eastern Cooperative Oncology Group perfomance worsened † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Hepatic enzyme increased † 1  0/28 (0.00%)  0/15 (0.00%)  3/225 (1.33%)  2/114 (1.75%) 
Liver function test abnormal † 1  1/28 (3.57%)  0/15 (0.00%)  5/225 (2.22%)  3/114 (2.63%) 
Transaminases increased † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  1/28 (3.57%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Dehydration † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Fluid overload † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Hyperglycaemia † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Hypoglycaemia † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Hyponatraemia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  2/114 (1.75%) 
Metabolic acidosis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Back pain † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Bone pain † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Muscular weakness † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Musculoskeletal chest pain † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Myalgia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Osteolysis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pain in extremity † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma pancreas † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Basal cell carcinoma † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Colon cancer † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Liver carcinoma ruptured † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Malignant neoplasm progression † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Metastases to bone † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Metastases to spine † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Squamous cell carcinoma † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Transitional cell carcinoma † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Tumour embolism † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Tumour haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Nervous system disorders         
Cerebral haemorrhage † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Cerebrovascular accident † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Dizziness † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Encephalopathy † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Haemorrhage intracranial † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Hepatic encephalopathy † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Ischaemic stroke † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Radiculitis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Spinal cord compression † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Spinal cord paralysis † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Transient ischaemic attack † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Renal and urinary disorders         
Renal failure † 1  1/28 (3.57%)  0/15 (0.00%)  1/225 (0.44%)  1/114 (0.88%) 
Renal failure acute † 1  0/28 (0.00%)  0/15 (0.00%)  4/225 (1.78%)  1/114 (0.88%) 
Renal impairment † 1  0/28 (0.00%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Renal injury † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Urethral meatus stenosis † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Bronchial obstruction † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Cough † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
Dyspnoea † 1  0/28 (0.00%)  1/15 (6.67%)  4/225 (1.78%)  0/114 (0.00%) 
Dyspnoea exertional † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Hypoxia † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Pulmonary embolism † 1  0/28 (0.00%)  1/15 (6.67%)  1/225 (0.44%)  2/114 (1.75%) 
Respiratory failure † 1  1/28 (3.57%)  0/15 (0.00%)  3/225 (1.33%)  0/114 (0.00%) 
Pleural effusion † 1  1/28 (3.57%)  0/15 (0.00%)  0/225 (0.00%)  0/114 (0.00%) 
Vascular disorders         
Hypovolaemic shock † 1  0/28 (0.00%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Shock haemorrhagic † 1  0/28 (0.00%)  0/15 (0.00%)  0/225 (0.00%)  1/114 (0.88%) 
1
Term from vocabulary, MedDRA 12.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tivantinib 240 mg BID Cohort Placebo Matching 240 mg BID Cohort Tivantinib 120 mg BID Cohort Placebo Matching 120 mg BID Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/28 (60.71%)   10/15 (66.67%)   214/225 (95.11%)   108/114 (94.74%) 
Blood and lymphatic system disorders         
Anaemia † 1  11/28 (39.29%)  2/15 (13.33%)  42/225 (18.67%)  17/114 (14.91%) 
Neutropenia † 1  15/28 (53.57%)  2/15 (13.33%)  28/225 (12.44%)  5/114 (4.39%) 
Leukopenia † 1  0/28 (0.00%)  1/15 (6.67%)  4/225 (1.78%)  1/114 (0.88%) 
Thrombocytopenia † 1  3/28 (10.71%)  0/15 (0.00%)  5/225 (2.22%)  5/114 (4.39%) 
Cardiac disorders         
Bradycardia † 1  3/28 (10.71%)  0/15 (0.00%)  31/225 (13.78%)  0/114 (0.00%) 
Sinus bradycardia † 1  0/28 (0.00%)  0/15 (0.00%)  12/225 (5.33%)  3/114 (2.63%) 
Myocardial infarction † 1  2/28 (7.14%)  0/15 (0.00%)  2/225 (0.89%)  1/114 (0.88%) 
Gastrointestinal disorders         
Abdominal distension † 1  0/28 (0.00%)  0/15 (0.00%)  11/225 (4.89%)  8/114 (7.02%) 
Abdominal pain † 1  3/28 (10.71%)  2/15 (13.33%)  47/225 (20.89%)  32/114 (28.07%) 
Abdominal pain upper † 1  3/28 (10.71%)  1/15 (6.67%)  26/225 (11.56%)  15/114 (13.16%) 
Ascites † 1  6/28 (21.43%)  7/15 (46.67%)  46/225 (20.44%)  24/114 (21.05%) 
Constipation † 1  1/28 (3.57%)  1/15 (6.67%)  29/225 (12.89%)  14/114 (12.28%) 
Diarrhoea † 1  4/28 (14.29%)  2/15 (13.33%)  50/225 (22.22%)  17/114 (14.91%) 
Dyspepsia † 1  2/28 (7.14%)  1/15 (6.67%)  12/225 (5.33%)  8/114 (7.02%) 
Nausea † 1  4/28 (14.29%)  1/15 (6.67%)  50/225 (22.22%)  13/114 (11.40%) 
Vomiting † 1  2/28 (7.14%)  0/15 (0.00%)  26/225 (11.56%)  13/114 (11.40%) 
Dry mouth † 1  0/28 (0.00%)  1/15 (6.67%)  4/225 (1.78%)  3/114 (2.63%) 
Gastric haemorrhage † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  2/114 (1.75%) 
Haematemesis † 1  2/28 (7.14%)  0/15 (0.00%)  1/225 (0.44%)  2/114 (1.75%) 
Haemorrhage ascites † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Melaena † 1  0/28 (0.00%)  1/15 (6.67%)  3/225 (1.33%)  2/114 (1.75%) 
Oesophageal varices haemorrhage † 1  1/28 (3.57%)  2/15 (13.33%)  6/225 (2.67%)  4/114 (3.51%) 
Peritoneal haemorrhage † 1  0/28 (0.00%)  1/15 (6.67%)  2/225 (0.89%)  1/114 (0.88%) 
Rectal haemorrhage † 1  2/28 (7.14%)  0/15 (0.00%)  2/225 (0.89%)  0/114 (0.00%) 
Stomatitis † 1  4/28 (14.29%)  0/15 (0.00%)  7/225 (3.11%)  3/114 (2.63%) 
Umbilical hernia † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
General disorders         
Asthenia † 1  8/28 (28.57%)  2/15 (13.33%)  48/225 (21.33%)  25/114 (21.93%) 
Fatigue † 1  1/28 (3.57%)  4/15 (26.67%)  58/225 (25.78%)  31/114 (27.19%) 
General physical health deterioration † 1  0/28 (0.00%)  1/15 (6.67%)  15/225 (6.67%)  5/114 (4.39%) 
Oedema peripheral † 1  7/28 (25.00%)  1/15 (6.67%)  54/225 (24.00%)  19/114 (16.67%) 
Pyrexia † 1  6/28 (21.43%)  1/15 (6.67%)  28/225 (12.44%)  15/114 (13.16%) 
Device dislocation † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Disease progression † 1  2/28 (7.14%)  0/15 (0.00%)  1/225 (0.44%)  0/114 (0.00%) 
Oedema † 1  1/28 (3.57%)  1/15 (6.67%)  1/225 (0.44%)  4/114 (3.51%) 
Pain † 1  1/28 (3.57%)  1/15 (6.67%)  4/225 (1.78%)  2/114 (1.75%) 
Hepatobiliary disorders         
Hepatic failure † 1  1/28 (3.57%)  2/15 (13.33%)  5/225 (2.22%)  0/114 (0.00%) 
Hyperbilirubinaemia † 1  2/28 (7.14%)  0/15 (0.00%)  6/225 (2.67%)  3/114 (2.63%) 
Jaundice † 1  0/28 (0.00%)  2/15 (13.33%)  6/225 (2.67%)  4/114 (3.51%) 
Liver injury † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Infections and infestations         
Nasopharyngitis † 1  0/28 (0.00%)  0/15 (0.00%)  9/225 (4.00%)  7/114 (6.14%) 
Gastroenteritis † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  3/114 (2.63%) 
Pharyngitis † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Rhinitis † 1  0/28 (0.00%)  1/15 (6.67%)  1/225 (0.44%)  0/114 (0.00%) 
Injury, poisoning and procedural complications         
Fall † 1  0/28 (0.00%)  1/15 (6.67%)  8/225 (3.56%)  3/114 (2.63%) 
Humerus fracture † 1  0/28 (0.00%)  1/15 (6.67%)  2/225 (0.89%)  0/114 (0.00%) 
Investigations         
Alanine aminotransferase increased † 1  1/28 (3.57%)  2/15 (13.33%)  8/225 (3.56%)  7/114 (6.14%) 
Aspartate aminotransferase increased † 1  1/28 (3.57%)  3/15 (20.00%)  14/225 (6.22%)  10/114 (8.77%) 
Blood bilirubin increased † 1  1/28 (3.57%)  0/15 (0.00%)  12/225 (5.33%)  6/114 (5.26%) 
Blood alkaline phosphatase increased † 1  0/28 (0.00%)  1/15 (6.67%)  6/225 (2.67%)  5/114 (4.39%) 
Blood creatinine increased † 1  0/28 (0.00%)  2/15 (13.33%)  3/225 (1.33%)  3/114 (2.63%) 
Blood uric acid increased † 1  1/28 (3.57%)  1/15 (6.67%)  1/225 (0.44%)  0/114 (0.00%) 
Gamma-glutamyltransferase increased † 1  2/28 (7.14%)  1/15 (6.67%)  5/225 (2.22%)  3/114 (2.63%) 
Lymphocyte count decreased † 1  0/28 (0.00%)  1/15 (6.67%)  3/225 (1.33%)  0/114 (0.00%) 
Platelet count decreased † 1  5/28 (17.86%)  1/15 (6.67%)  5/225 (2.22%)  5/114 (4.39%) 
Weight decreased † 1  0/28 (0.00%)  1/15 (6.67%)  11/225 (4.89%)  3/114 (2.63%) 
Weight increased † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  1/114 (0.88%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  2/28 (7.14%)  3/15 (20.00%)  36/225 (16.00%)  21/114 (18.42%) 
Hyperkalaemia † 1  2/28 (7.14%)  1/15 (6.67%)  7/225 (3.11%)  2/114 (1.75%) 
Hypoalbuminaemia † 1  0/28 (0.00%)  1/15 (6.67%)  6/225 (2.67%)  2/114 (1.75%) 
Hypokalaemia † 1  0/28 (0.00%)  1/15 (6.67%)  2/225 (0.89%)  0/114 (0.00%) 
Hyponatraemia † 1  0/28 (0.00%)  1/15 (6.67%)  8/225 (3.56%)  4/114 (3.51%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  0/28 (0.00%)  2/15 (13.33%)  19/225 (8.44%)  4/114 (3.51%) 
Back pain † 1  1/28 (3.57%)  0/15 (0.00%)  19/225 (8.44%)  14/114 (12.28%) 
Musculoskeletal pain † 1  1/28 (3.57%)  1/15 (6.67%)  8/225 (3.56%)  8/114 (7.02%) 
Muscle spasms † 1  0/28 (0.00%)  1/15 (6.67%)  11/225 (4.89%)  3/114 (2.63%) 
Muscular weakness † 1  0/28 (0.00%)  2/15 (13.33%)  5/225 (2.22%)  2/114 (1.75%) 
Musculoskeletal chest pain † 1  0/28 (0.00%)  2/15 (13.33%)  2/225 (0.89%)  2/114 (1.75%) 
Pain in extremity † 1  0/28 (0.00%)  1/15 (6.67%)  9/225 (4.00%)  5/114 (4.39%) 
Nervous system disorders         
Dizziness † 1  1/28 (3.57%)  1/15 (6.67%)  16/225 (7.11%)  3/114 (2.63%) 
Headache † 1  0/28 (0.00%)  0/15 (0.00%)  13/225 (5.78%)  3/114 (2.63%) 
Encephalopathy † 1  0/28 (0.00%)  1/15 (6.67%)  3/225 (1.33%)  3/114 (2.63%) 
Paraesthesia † 1  0/28 (0.00%)  1/15 (6.67%)  3/225 (1.33%)  1/114 (0.88%) 
Psychiatric disorders         
Bradyphrenia † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Insomnia † 1  0/28 (0.00%)  2/15 (13.33%)  10/225 (4.44%)  5/114 (4.39%) 
Urethral meatus stenosis † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Reproductive system and breast disorders         
Testicular pain † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  5/28 (17.86%)  0/15 (0.00%)  32/225 (14.22%)  12/114 (10.53%) 
Dyspnoea † 1  2/28 (7.14%)  2/15 (13.33%)  22/225 (9.78%)  6/114 (5.26%) 
Dysphonia † 1  0/28 (0.00%)  1/15 (6.67%)  3/225 (1.33%)  3/114 (2.63%) 
Nasal congestion † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  1/114 (0.88%) 
Pulmonary embolism † 1  0/28 (0.00%)  1/15 (6.67%)  2/225 (0.89%)  3/114 (2.63%) 
Skin and subcutaneous tissue disorders         
Pruritus † 1  2/28 (7.14%)  2/15 (13.33%)  24/225 (10.67%)  21/114 (18.42%) 
Rash † 1  0/28 (0.00%)  0/15 (0.00%)  9/225 (4.00%)  6/114 (5.26%) 
Alopecia † 1  7/28 (25.00%)  0/15 (0.00%)  5/225 (2.22%)  0/114 (0.00%) 
Skin lesion † 1  0/28 (0.00%)  1/15 (6.67%)  1/225 (0.44%)  1/114 (0.88%) 
Vascular disorders         
Hypertension † 1  0/28 (0.00%)  1/15 (6.67%)  19/225 (8.44%)  5/114 (4.39%) 
Bleeding varicose vein † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
Hypotension † 1  2/28 (7.14%)  0/15 (0.00%)  3/225 (1.33%)  5/114 (4.39%) 
Intra-abdominal haematoma † 1  0/28 (0.00%)  1/15 (6.67%)  0/225 (0.00%)  0/114 (0.00%) 
1
Term from vocabulary, MedDRA 12.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sankyo
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT01755767    
Other Study ID Numbers: ARQ197-A-U303
2012-003308-10 ( EudraCT Number )
First Submitted: December 19, 2012
First Posted: December 24, 2012
Results First Submitted: June 10, 2020
Results First Posted: July 15, 2020
Last Update Posted: April 6, 2021