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Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Advanced Hepatocellular Carcinoma (MK-3475-224/KEYNOTE-224)

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ClinicalTrials.gov Identifier: NCT02702414
Recruitment Status : Completed
First Posted : March 8, 2016
Results First Posted : April 4, 2022
Last Update Posted : October 18, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Intervention Biological: Pembrolizumab
Enrollment 156
Recruitment Details

This study had 2 cohorts with each cohort starting treatment at a different time period during the study.

One participant allocated to Cohort 1 withdrew from the study before receiving treatment. This participant was not eligible for safety or efficacy analysis.
Pre-assignment Details

Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. There was 1 participant in Cohort 1 and no participants in Cohort 2 who received second course treatment with pembrolizumab.

Per protocol, final analyses of all outcome measures were planned to be performed during the first course of therapy and collection of adverse events and all-cause mortality were planned to be done in both first and second courses.
Arm/Group Title Cohort 1: Hepatocellular Carcinoma (HCC)-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description Participants with previously systemically treated HCC received a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Period Title: Overall Study
Started 105 51
Treated 104 51
Completed 0 0
Not Completed 105 51
Reason Not Completed
Death             77             34
Lost to Follow-up             0             1
Withdrawal by Subject             0             1
Participants Ongoing in Study             27             15
Not Treated             1             0
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve Total
Hide Arm/Group Description Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. Total of all reporting groups
Overall Number of Baseline Participants 104 51 155
Hide Baseline Analysis Population Description
The baseline population included all participants that received ≥1 dose of pembrolizumab.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 104 participants 51 participants 155 participants
67.4  (8.2) 67.7  (10.3) 67.5  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 51 participants 155 participants
Female
18
  17.3%
7
  13.7%
25
  16.1%
Male
86
  82.7%
44
  86.3%
130
  83.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 51 participants 155 participants
Hispanic or Latino
2
   1.9%
2
   3.9%
4
   2.6%
Not Hispanic or Latino
98
  94.2%
45
  88.2%
143
  92.3%
Unknown or Not Reported
4
   3.8%
4
   7.8%
8
   5.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 51 participants 155 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
14
  13.5%
2
   3.9%
16
  10.3%
Native Hawaiian or Other Pacific Islander
1
   1.0%
0
   0.0%
1
   0.6%
Black or African American
3
   2.9%
1
   2.0%
4
   2.6%
White
84
  80.8%
48
  94.1%
132
  85.2%
More than one race
1
   1.0%
0
   0.0%
1
   0.6%
Unknown or Not Reported
1
   1.0%
0
   0.0%
1
   0.6%
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
18.3
(11.4 to 27.1)
15.7
(7.0 to 28.6)
2.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target and non-target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed, started a new anti-cancer therapy, been lost to follow-up, or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment and who had a confirmed CR or confirmed PR during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 19 8
Median (95% Confidence Interval)
Unit of Measure: Months
21.0 [1] 
(10.7 to NA)
16.2 [1] 
(3.1 to NA)
[1]
NA=upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse
3.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the percentage of participants who had a CR (disappearance of all target and non-target lesions), PR (at least a 30% decrease in the sum of diameters of target and non-target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions.]). CR, PR, and SD were evaluated per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered as participants whose disease was not under control. The percentage of participants who experienced a confirmed CR, PR, or SD is reported.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
61.5
(51.5 to 70.9)
56.9
(42.2 to 70.7)
4.Secondary Outcome
Title Time to Progression (TTP)
Hide Description TTP was defined as the time from the first dose to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. The TTP was analyzed using the product-limit (Kaplan-Meier) method for censored data. TTP per RECIST 1.1 is presented.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Median (95% Confidence Interval)
Unit of Measure: Months
4.8
(3.9 to 7.0)
4.4
(2.5 to 8.6)
5.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as the time from the first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. PFS is presented.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Median (95% Confidence Interval)
Unit of Measure: Months
4.9
(3.5 to 6.7)
4.3
(2.1 to 7.8)
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was determined for all participants and was defined as the time from the first dose to death due to any cause. Participants were censored at the last known alive date. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. The OS is presented.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Median (95% Confidence Interval)
Unit of Measure: Months
13.2
(9.7 to 15.3)
16.9
(8.3 to 23.1)
7.Secondary Outcome
Title Number of Participants Who Experienced At Least One Adverse Event (AE)
Hide Description An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experienced at least one AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Measure Type: Count of Participants
Unit of Measure: Participants
101
  97.1%
49
  96.1%
8.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Hide Description An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who discontinued study treatment due to an AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only.
Time Frame Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment during the first course of therapy.
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve
Hide Arm/Group Description:
Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment.
Overall Number of Participants Analyzed 104 51
Measure Type: Count of Participants
Unit of Measure: Participants
23
  22.1%
8
  15.7%
Time Frame Cohort 1 First Course: Up to approximately 34 months Cohort 2 First Course: Up to approximately 28 months Cohort 1 Second Course: Up to approximately 5 months
Adverse Event Reporting Description All-cause mortality (ACM)=all allocated participants; AEs=all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression (NP), malignant NP, and disease progression not related to treatment were excluded. MedDRA version: Cohort 1=22.0; Cohort 2 =23.1. Per protocol, collection of AEs and ACM were planned for both first and second courses.
 
Arm/Group Title Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve Cohort 1: HCC-Prior Systemic Therapy With Sorafenib-Second Course Cohort 2: HCC-Systemic Therapy Naïve-Second Course
Hide Arm/Group Description Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. Participants from Cohort 1 who met the criteria for re-treatment received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 17 administrations. Participants from Cohort 2 who met the criteria for re-treatment received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 17 administrations
All-Cause Mortality
Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve Cohort 1: HCC-Prior Systemic Therapy With Sorafenib-Second Course Cohort 2: HCC-Systemic Therapy Naïve-Second Course
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   77/105 (73.33%)      34/51 (66.67%)      0/1 (0.00%)      0/0    
Hide Serious Adverse Events
Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve Cohort 1: HCC-Prior Systemic Therapy With Sorafenib-Second Course Cohort 2: HCC-Systemic Therapy Naïve-Second Course
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/104 (42.31%)      21/51 (41.18%)      0/1 (0.00%)      0/0    
Blood and lymphatic system disorders         
Anaemia † 1  3/104 (2.88%)  4 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Cardiac disorders         
Acute myocardial infarction † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Atrioventricular block second degree † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cardiac failure † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cardiogenic shock † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Chronic left ventricular failure † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Myocarditis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ventricular fibrillation † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Endocrine disorders         
Adrenal insufficiency † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypophysitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Eye disorders         
Retinal vein occlusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastrointestinal disorders         
Abdominal pain † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ascites † 1  4/104 (3.85%)  4 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Autoimmune colitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Colitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Constipation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastric ulcer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastritis haemorrhagic † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastrooesophageal reflux disease † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Melaena † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Oesophageal varices haemorrhage † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Umbilical hernia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Upper gastrointestinal haemorrhage † 1  3/104 (2.88%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Varices oesophageal † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
General disorders         
Asthenia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Chest pain † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Death † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Fatigue † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
General physical health deterioration † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Multiple organ dysfunction syndrome † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pyrexia † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ulcer haemorrhage † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatobiliary disorders         
Hepatic failure † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatic haemorrhage † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatocellular injury † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Immune-mediated hepatitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Jaundice † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Jaundice cholestatic † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Infections and infestations         
Bacteraemia † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cellulitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Device related infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastroenteritis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Gastroenteritis viral † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Lung infection † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pneumonia bacterial † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Sepsis † 1  3/104 (2.88%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Septic shock † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Urinary tract infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Viral infection † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Large intestine infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Injury, poisoning and procedural complications         
Hip fracture † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Investigations         
Alanine aminotransferase increased † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Aspartate aminotransferase increased † 1  4/104 (3.85%)  4 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Blood bilirubin increased † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Blood creatinine increased † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Metabolism and nutrition disorders         
Diabetic ketoacidosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Diabetic metabolic decompensation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Failure to thrive † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyperkalaemia † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Type 1 diabetes mellitus † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Musculoskeletal and connective tissue disorders         
Myositis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pathological fracture † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Colon cancer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Squamous cell carcinoma † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Tumour necrosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Nervous system disorders         
Encephalopathy † 1  0/104 (0.00%)  0 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Hepatic encephalopathy † 1  1/104 (0.96%)  2 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ischaemic stroke † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Presyncope † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Radiculopathy † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Syncope † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Renal and urinary disorders         
Acute kidney injury † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Renal failure † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Respiratory, thoracic and mediastinal disorders         
Dyspnoea † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pleural effusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pulmonary embolism † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Skin and subcutaneous tissue disorders         
Lichenoid keratosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rash † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Vascular disorders         
Hypovolaemic shock † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
1
Term from vocabulary, MedDRA 22.0, 23.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1: HCC-Prior Systemic Therapy With Sorafenib Cohort 2: HCC-Systemic Therapy Naïve Cohort 1: HCC-Prior Systemic Therapy With Sorafenib-Second Course Cohort 2: HCC-Systemic Therapy Naïve-Second Course
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   99/104 (95.19%)      49/51 (96.08%)      1/1 (100.00%)      0/0    
Blood and lymphatic system disorders         
Anaemia † 1  11/104 (10.58%)  12 1/51 (1.96%)  1 1/1 (100.00%)  1 0/0  0
Iron deficiency anaemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Leukocytosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Leukopenia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Neutropenia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Thrombocytopenia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Microcytic anaemia † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cardiac disorders         
Angina pectoris † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Arrhythmia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Atrial fibrillation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Bradycardia † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cardiac failure † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Palpitations † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pericardial effusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Ear and labyrinth disorders         
Ear discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Ear pain † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Paraesthesia ear † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Tinnitus † 1  0/104 (0.00%)  0 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Vertigo † 1  2/104 (1.92%)  2 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Endocrine disorders         
Hypothyroidism † 1  8/104 (7.69%)  9 6/51 (11.76%)  6 0/1 (0.00%)  0 0/0  0
Goitre † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyperthyroidism † 1  1/104 (0.96%)  1 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Hypophysitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Thyroiditis † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Adrenal insufficiency † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Eye disorders         
Cataract † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dry eye † 1  4/104 (3.85%)  4 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Erythema of eyelid † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Retinal detachment † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Retinal vein occlusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vision blurred † 1  3/104 (2.88%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Visual acuity reduced † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Gastrointestinal disorders         
Abdominal pain † 1  16/104 (15.38%)  18 8/51 (15.69%)  9 1/1 (100.00%)  1 0/0  0
Abdominal pain upper † 1  10/104 (9.62%)  13 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Ascites † 1  12/104 (11.54%)  12 6/51 (11.76%)  6 0/1 (0.00%)  0 0/0  0
Constipation † 1  18/104 (17.31%)  18 4/51 (7.84%)  4 0/1 (0.00%)  0 0/0  0
Diarrhoea † 1  17/104 (16.35%)  21 13/51 (25.49%)  15 1/1 (100.00%)  1 0/0  0
Dry mouth † 1  5/104 (4.81%)  5 4/51 (7.84%)  4 0/1 (0.00%)  0 0/0  0
Dyspepsia † 1  3/104 (2.88%)  3 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Nausea † 1  21/104 (20.19%)  21 4/51 (7.84%)  6 0/1 (0.00%)  0 0/0  0
Varices oesophageal † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 1/1 (100.00%)  1 0/0  0
Vomiting † 1  9/104 (8.65%)  15 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Abdominal discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Abdominal distension † 1  3/104 (2.88%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Abdominal pain lower † 1  3/104 (2.88%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Abdominal tenderness † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Aphthous ulcer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Colitis † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Dental caries † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Dysphagia † 1  3/104 (2.88%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Faeces soft † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Flatulence † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastric ulcer † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Gastritis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gastrooesophageal reflux disease † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gingival pain † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Haemorrhoids † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Impaired gastric emptying † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Inguinal hernia † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Lip dry † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Lip ulceration † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Melaena † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Noninfective gingivitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Stomatitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Toothache † 1  2/104 (1.92%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
General disorders         
Asthenia † 1  16/104 (15.38%)  19 7/51 (13.73%)  8 1/1 (100.00%)  1 0/0  0
Fatigue † 1  30/104 (28.85%)  40 21/51 (41.18%)  23 0/1 (0.00%)  0 0/0  0
Mucosal inflammation † 1  2/104 (1.92%)  3 3/51 (5.88%)  4 0/1 (0.00%)  0 0/0  0
Oedema peripheral † 1  19/104 (18.27%)  20 14/51 (27.45%)  15 0/1 (0.00%)  0 0/0  0
Pyrexia † 1  5/104 (4.81%)  6 5/51 (9.80%)  6 0/1 (0.00%)  0 0/0  0
Catheter site eczema † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Chest discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Chest pain † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Chills † 1  4/104 (3.85%)  4 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Feeling cold † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gait disturbance † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
General physical health deterioration † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Influenza like illness † 1  4/104 (3.85%)  7 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Injection site swelling † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Malaise † 1  3/104 (2.88%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Mucosal dryness † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Peripheral swelling † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Temperature intolerance † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hepatobiliary disorders         
Cholecystitis acute † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Cholelithiasis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatic cirrhosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hepatic pain † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatic vein thrombosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatomegaly † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hyperbilirubinaemia † 1  4/104 (3.85%)  5 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Portal vein occlusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Portal vein thrombosis † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Immune system disorders         
Contrast media allergy † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hypersensitivity † 1  0/104 (0.00%)  0 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Seasonal allergy † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Infections and infestations         
Nasopharyngitis † 1  3/104 (2.88%)  3 4/51 (7.84%)  4 0/1 (0.00%)  0 0/0  0
Rhinitis † 1  1/104 (0.96%)  1 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Urinary tract infection † 1  3/104 (2.88%)  3 3/51 (5.88%)  4 0/1 (0.00%)  0 0/0  0
Abdominal infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Bronchiolitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Bronchitis † 1  4/104 (3.85%)  4 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Candida infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Clostridium difficile infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Conjunctivitis † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Cytomegalovirus infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Enteritis infectious † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Escherichia urinary tract infection † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Fungal skin infection † 1  2/104 (1.92%)  2 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Gastroenteritis † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Genital infection fungal † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Herpes zoster † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Influenza † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Laryngitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Lower respiratory tract infection † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Oral bacterial infection † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Oral candidiasis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Oral herpes † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Perichondritis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Peritonitis bacterial † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pharyngitis † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pneumonia † 1  3/104 (2.88%)  3 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Rash pustular † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Respiratory tract infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Respiratory tract infection viral † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Sinusitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Soft tissue infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Tracheitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Tooth infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Upper respiratory tract infection † 1  5/104 (4.81%)  5 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Viral infection † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vulvovaginal candidiasis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vulvovaginal mycotic infection † 1  1/104 (0.96%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Injury, poisoning and procedural complications         
Contusion † 1  4/104 (3.85%)  5 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Eye contusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Eyelid injury † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Fall † 1  5/104 (4.81%)  6 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Limb injury † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Muscle strain † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Post procedural bile leak † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin abrasion † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Suture related complication † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Wound † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Wrist fracture † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Investigations         
Alanine aminotransferase increased † 1  13/104 (12.50%)  16 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Aspartate aminotransferase increased † 1  23/104 (22.12%)  27 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Blood alkaline phosphatase increased † 1  6/104 (5.77%)  7 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Blood bilirubin increased † 1  9/104 (8.65%)  10 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Serum ferritin decreased † 1  0/104 (0.00%)  0 0/51 (0.00%)  0 1/1 (100.00%)  1 0/0  0
Weight decreased † 1  6/104 (5.77%)  6 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Bilirubin conjugated increased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Blood creatine phosphokinase increased † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Blood creatinine increased † 1  2/104 (1.92%)  2 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Blood folate decreased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Blood testosterone decreased † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Blood thyroid stimulating hormone increased † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
C-reactive protein increased † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Gamma-glutamyltransferase increased † 1  4/104 (3.85%)  4 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Heart rate increased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Leukocyte alkaline phosphatase increased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Lymphocyte count decreased † 1  2/104 (1.92%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Myoglobin blood increased † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Neutrophil count decreased † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Platelet count decreased † 1  2/104 (1.92%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Prothrombin time shortened † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vitamin D decreased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Waist circumference increased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Weight increased † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
White blood cell count decreased † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Metabolism and nutrition disorders         
Decreased appetite † 1  16/104 (15.38%)  18 8/51 (15.69%)  9 0/1 (0.00%)  0 0/0  0
Hyperglycaemia † 1  3/104 (2.88%)  3 3/51 (5.88%)  3 0/1 (0.00%)  0 0/0  0
Hypokalaemia † 1  2/104 (1.92%)  2 3/51 (5.88%)  3 1/1 (100.00%)  1 0/0  0
Hypophosphataemia † 1  4/104 (3.85%)  4 1/51 (1.96%)  1 1/1 (100.00%)  1 0/0  0
Vitamin D deficiency † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 1/1 (100.00%)  1 0/0  0
Dehydration † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Diabetes mellitus † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Diabetes mellitus inadequate control † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Fluid overload † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Fluid retention † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyperammonaemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypercreatininaemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyperkalaemia † 1  5/104 (4.81%)  7 2/51 (3.92%)  4 0/1 (0.00%)  0 0/0  0
Hyperlipasaemia † 1  2/104 (1.92%)  7 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypoalbuminaemia † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hypocalcaemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypoglycaemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypomagnesaemia † 1  2/104 (1.92%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyponatraemia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Iron deficiency † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Malnutrition † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Type 2 diabetes mellitus † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Vitamin B12 deficiency † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  18/104 (17.31%)  22 5/51 (9.80%)  7 0/1 (0.00%)  0 0/0  0
Back pain † 1  8/104 (7.69%)  9 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Muscle spasms † 1  6/104 (5.77%)  8 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Myalgia † 1  8/104 (7.69%)  16 5/51 (9.80%)  6 0/1 (0.00%)  0 0/0  0
Arthritis † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Bone pain † 1  1/104 (0.96%)  1 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Chondrocalcinosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Costochondritis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Flank pain † 1  4/104 (3.85%)  4 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Joint stiffness † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Joint swelling † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Muscular weakness † 1  1/104 (0.96%)  1 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Musculoskeletal chest pain † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Musculoskeletal discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Musculoskeletal pain † 1  5/104 (4.81%)  9 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Musculoskeletal stiffness † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Osteoporosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pain in extremity † 1  4/104 (3.85%)  5 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Spondylitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Tendon disorder † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Tenosynovitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Hepatic cancer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Seborrhoeic keratosis † 1  2/104 (1.92%)  2 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Skin papilloma † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Nervous system disorders         
Dizziness † 1  4/104 (3.85%)  4 0/51 (0.00%)  0 1/1 (100.00%)  1 0/0  0
Headache † 1  7/104 (6.73%)  10 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ageusia † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Amnesia † 1  2/104 (1.92%)  2 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Ataxia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Balance disorder † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Brain oedema † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Carpal tunnel syndrome † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dizziness postural † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dysgeusia † 1  1/104 (0.96%)  1 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Head discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hepatic encephalopathy † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Memory impairment † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Migraine with aura † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Neuropathy peripheral † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Paraesthesia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Peripheral sensory neuropathy † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Sciatica † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Syncope † 1  1/104 (0.96%)  1 1/51 (1.96%)  2 0/1 (0.00%)  0 0/0  0
Taste disorder † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Psychiatric disorders         
Insomnia † 1  7/104 (6.73%)  7 4/51 (7.84%)  4 1/1 (100.00%)  1 0/0  0
Anxiety † 1  2/104 (1.92%)  2 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Confusional state † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Depressed mood † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Depression † 1  3/104 (2.88%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Libido decreased † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Mood altered † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Sleep disorder † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Renal and urinary disorders         
Acute kidney injury † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Chromaturia † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dysuria † 1  1/104 (0.96%)  1 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Haematuria † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Micturition urgency † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pollakiuria † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Proteinuria † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Renal failure † 1  1/104 (0.96%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Renal impairment † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Urinary incontinence † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Urinary retention † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Urine abnormality † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Reproductive system and breast disorders         
Balanoposthitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Breast discomfort † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Breast swelling † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Gynaecomastia † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Nipple pain † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Prostatitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Prostatomegaly † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Vaginal haemorrhage † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Respiratory, thoracic and mediastinal disorders         
Cough † 1  19/104 (18.27%)  21 8/51 (15.69%)  10 0/1 (0.00%)  0 0/0  0
Dyspnoea † 1  11/104 (10.58%)  15 6/51 (11.76%)  6 0/1 (0.00%)  0 0/0  0
Productive cough † 1  6/104 (5.77%)  6 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Asthma † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Bronchospasm † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Dysphonia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dyspnoea exertional † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Epistaxis † 1  2/104 (1.92%)  2 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Haemoptysis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hiccups † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Laryngeal inflammation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Nasal ulcer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Oropharyngeal pain † 1  3/104 (2.88%)  3 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Pleural effusion † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pleuritic pain † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pneumonitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Rhinorrhoea † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin and subcutaneous tissue disorders         
Night sweats † 1  6/104 (5.77%)  6 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Pruritus † 1  23/104 (22.12%)  28 6/51 (11.76%)  8 0/1 (0.00%)  0 0/0  0
Rash † 1  13/104 (12.50%)  18 5/51 (9.80%)  5 0/1 (0.00%)  0 0/0  0
Actinic keratosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Alopecia † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dermal cyst † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dermatitis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dermatitis acneiform † 1  3/104 (2.88%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Dermatitis contact † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Dry skin † 1  2/104 (1.92%)  2 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Eczema † 1  3/104 (2.88%)  3 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Eczema asteatotic † 1  2/104 (1.92%)  2 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Granulomatous dermatitis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hair colour changes † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hyperhidrosis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Hyperkeratosis † 1  2/104 (1.92%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Lichenoid keratosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Milia † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Palmar-plantar erythrodysaesthesia syndrome † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Pruritus generalised † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Psoriasis † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Purpura † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rash erythematous † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rash generalised † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rash macular † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rash maculo-papular † 1  5/104 (4.81%)  6 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Rash papular † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Rash pruritic † 1  2/104 (1.92%)  3 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Rosacea † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Skin burning sensation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin exfoliation † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Skin hyperpigmentation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin hypopigmentation † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin lesion † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Skin plaque † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Skin ulcer † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vitiligo † 1  0/104 (0.00%)  0 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Vascular disorders         
Deep vein thrombosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Embolism † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Haematoma † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hot flush † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Hypertension † 1  0/104 (0.00%)  0 2/51 (3.92%)  2 0/1 (0.00%)  0 0/0  0
Orthostatic hypotension † 1  1/104 (0.96%)  1 1/51 (1.96%)  1 0/1 (0.00%)  0 0/0  0
Peripheral venous disease † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Vena cava thrombosis † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
Venous occlusion † 1  1/104 (0.96%)  1 0/51 (0.00%)  0 0/1 (0.00%)  0 0/0  0
1
Term from vocabulary, MedDRA 22.0, 23.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT02702414    
Other Study ID Numbers: 3475-224
MK-3475-224 ( Other Identifier: Merck )
KEYNOTE-224 ( Other Identifier: Merck )
163434 ( Other Identifier: JAPIC-CTI )
2015-004566-28 ( EudraCT Number )
First Submitted: March 3, 2016
First Posted: March 8, 2016
Results First Submitted: January 7, 2022
Results First Posted: April 4, 2022
Last Update Posted: October 18, 2023