Phase I/II Comparison of Efficacy and Safety of BIBF 1120... | NCT01004003 | Trialant
NCT01004003
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Oct 26, 2017Actual
Enrollment
125Actual
Phase
Phase 2
Conditions
Carcinoma, Hepatocellular
Interventions
Sorafenib
BIBF 1120
Countries
Austria
France
Germany
Hungary
Netherlands
Poland
Romania
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01004003
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1199.37
Secondary IDs
ID
Type
Description
Link
2009-011925-14
EudraCT Number
EudraCT
Brief Title
Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Official Title
A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Sep 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 22, 2009Actual
Primary Completion Date
Jul 14, 2014Actual
Completion Date
Oct 12, 2016Actual
First Submitted Date
Oct 12, 2009
First Submission Date that Met QC Criteria
Oct 28, 2009
First Posted Date
Oct 29, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 9, 2015
Results First Submitted that Met QC Criteria
Jul 9, 2015
Results First Posted Date
Aug 7, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Aug 18, 2014
Certification/Extension First Submitted that Passed QC Review
Aug 18, 2014
Certification/Extension First Posted Date
Aug 20, 2014Estimated
Last Update Submitted Date
Sep 25, 2017
Last Update Posted Date
Oct 26, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC patients
Detailed Description
Not provided
Conditions Module
Conditions
Carcinoma, Hepatocellular
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
125Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
BIBF 1120
Experimental
Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID)
Drug: BIBF 1120
Sorafenib
Active Comparator
Drug: Sorafenib
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Sorafenib
Drug
Sorafenib
BIBF 1120
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Maximum Tolerated Dose in Phase I
The MTD was defined as the highest dose studied for which the incidence of dose limiting toxicities (DLTs) was 0/3 or less than 2/6 patients during the first treatment course.
4 weeks
Time to Progression (TTP) in Phase II
TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.
From randomization until data cut-off (15 July 2014); Up to 1031 days
Secondary Outcomes
Measure
Description
Time Frame
Incidence of Dose Limiting Toxicity in Phase I
Number of patients with dose limiting toxicity are presented
4 weeks
Objective Tumour Response by RECIST
Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.
95% Confidence Interval presented below are computed by Clopper and Pearson method.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable to curative surgery or loco-regional therapy (RFA, percutaneous ethanol injection (PEI), TACE)
Age 18 years or older
Eastern Cooperative Oncology Group performance score of 2 or less
Child-Pugh score A (score 5-6)
At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only)
In case a measurable lesion was previously treated by loco-regional therapy (RFA, PEI, TACE or RT) , this lesion must have to be documented as progression according to RECIST 1.0 by CT or MRI (this criterion is limited to phase II only).
Time interval from last local therapy (e.g. radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to start of study treatment
Written informed consent consistent with International Conference on Harmonisation/ Good Clinical Practice (ICH-GCP) and local legislation
Exclusion criteria:
Prior systemic therapy for HCC
Fibrolamellar hepatocellular carcinoma (HCC)
Bilirubin greater than 1.5 times ULN
AST or ALT greater than 2 times ULN
Uncontrolled or refractory ascites to adequate medical therapy
Hepatic encephalopathy more than grade 1 according to Child-Pugh criteria
Prothrombin time international normalized ratio greater than 2.3, or prothrombin time more than 6 seconds prolonged than control
Absolute neutrophil count less than 1000 /µL
Platelet count less than 60000 /µL
Hemoglobin less than 9 g/dL
Serum creatinine greater than 1.5 times Upper Limit of Normal (ULN)
Proteinuria of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
Variceal bleeding within last 6 months prior to start of study treatment
History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
Known inherited predisposition to bleeding or thrombosis
Significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, blood pressure > 150/90 mmHg), unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > class II according to New York Heart Association (NYHA), serious cardiac arrhythmia, pericardial effusion)
Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =< 325mg per day)
Major surgery within 4 weeks prior to start of study treatment
Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
Known serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least twelve months after end of active therapy
Current alcohol abuse or drug abuse that would limit pt ability to comply with protocol
Symptomatic central nervous system (CNS) metastasis
Life expectancy less than 12 weeks
Patient unable to take oral medication
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Boehringer Ingelheim
Boehringer Ingelheim
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
1199.37.43001 Boehringer Ingelheim Investigational Site
Vienna
Austria
1199.37.43002 Boehringer Ingelheim Investigational Site
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase 1 Group 1, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD). Group 1 patients had a baseline Child-Pugh score of 5 or 6, and aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2 times the upper limit of normal (ULN).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Slovakia
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug
Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data
BIBF 1120
From randomization until data cut-off (15 July 2014); Up to 1031 days
Progression Free Survival (PFS)
PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.
From randomization until data cut-off (15 July 2014); Up to 1031 days
Overall Survival
Overall survival was defined as the duration from date of randomisation to the date of death.
From randomization until data cut-off (15 July 2014); Up to 1031 days
Vienna
Austria
1199.37.33001 Boehringer Ingelheim Investigational Site
Paris
France
1199.37.33002 Boehringer Ingelheim Investigational Site
Paris
France
1199.37.49008 Boehringer Ingelheim Investigational Site
Berlin
Germany
1199.37.49009 Boehringer Ingelheim Investigational Site
Erlangen
Germany
1199.37.49002 Boehringer Ingelheim Investigational Site
Freiburg im Breisgau
Germany
1199.37.49001 Boehringer Ingelheim Investigational Site
Hanover
Germany
1199.37.49010 Boehringer Ingelheim Investigational Site
Heidelberg
Germany
1199.37.49005 Boehringer Ingelheim Investigational Site
Jena
Germany
1199.37.49004 Boehringer Ingelheim Investigational Site
Magdeburg
Germany
1199.37.49003 Boehringer Ingelheim Investigational Site
München
Germany
1199.37.49006 Boehringer Ingelheim Investigational Site
Tübingen
Germany
1199.37.36001 Boehringer Ingelheim Investigational Site
Debrecen
Hungary
1199.37.31002 Boehringer Ingelheim Investigational Site
Leiden
Netherlands
1199.37.31001 Boehringer Ingelheim Investigational Site
Utrecht
Netherlands
1199.37.48002 Boehringer Ingelheim Investigational Site
Olsztyn
Poland
1199.37.48001 Boehringer Ingelheim Investigational Site
Warsaw
Poland
1199.37.48003 Boehringer Ingelheim Investigational Site
Warsaw
Poland
1199.37.40002 Boehringer Ingelheim Investigational Site
Bucharest
Romania
1199.37.40003 Boehringer Ingelheim Investigational Site
Cluj-Napoca
Romania
1199.37.44001 Boehringer Ingelheim Investigational Site
Edgbaston, Birmingham
United Kingdom
1199.37.44005 Boehringer Ingelheim Investigational Site
Glasgow
United Kingdom
1199.37.44008 Boehringer Ingelheim Investigational Site
Liverpool
United Kingdom
1199.37.44002 Boehringer Ingelheim Investigational Site
London
United Kingdom
1199.37.44003 Boehringer Ingelheim Investigational Site
London
United Kingdom
1199.37.44006 Boehringer Ingelheim Investigational Site
Manchester
United Kingdom
1199.37.44004 Boehringer Ingelheim Investigational Site
Nottingham
United Kingdom
FG001
Phase I Group 1, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
FG002
Phase I Group 1, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
FG003
Phase I Group 2, 50mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 50 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
FG004
Phase I Group 2, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
FG005
Phase I Group 2, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
FG006
Phase I Group 2, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
FG007
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
FG008
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
FG0006 subjects
FG0013 subjects
FG0024 subjects
FG0033 subjects
FG0044 subjects
FG0054 subjects
FG0068 subjects
FG00762 subjects
FG00831 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0072 subjectsOn-treatment at analysis cut-off date (15 July 2014).
FG0081 subjectsOn-treatment at analysis cut-off date (15 July 2014).
NOT COMPLETED
FG0006 subjects
FG0013 subjects
FG0024 subjects
FG0033 subjects
FG0044 subjects
FG0054 subjects
FG0068 subjects
FG00760 subjects
FG00830 subjects
Type
Comment
Reasons
Progressive disease
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0042 subjects
FG0051 subjects
FG0061 subjects
FG00739 subjects
FG00822 subjects
Adverse Event
FG0004 subjects
FG0012 subjects
FG0023 subjects
FG0033 subjects
FG004
Refused to continue taking trial med.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Treated set which included all patients who received at least one single dose of trial medication.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase 1 Group 1, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD). Group 1 patients had a baseline Child-Pugh score of 5 or 6, and aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2 times the upper limit of normal (ULN).
BG001
Phase I Group 1, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
BG002
Phase I Group 1, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
BG003
Phase I Group 2, 50mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 50 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
BG004
Phase I Group 2, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
BG005
Phase I Group 2, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
BG006
Phase I Group 2, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
BG007
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
BG008
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
BG009
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0013
BG0024
BG0033
BG0044
BG0054
BG0068
BG00762
BG00831
BG009125
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00069.7± 6.8
BG00165.0± 7.8
BG00266.5± 4.0
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0011
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Maximum Tolerated Dose in Phase I
The MTD was defined as the highest dose studied for which the incidence of dose limiting toxicities (DLTs) was 0/3 or less than 2/6 patients during the first treatment course.
Treated set which included all patients who received at least one single dose of trial medication, including phase I patients from the dose escalation part that were not replaced for MTD determination.
Posted
Number
mg bid
4 weeks
ID
Title
Description
OG000
Group 1
Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN)
OG001
Group 2
Patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Units
Counts
Participants
OG0009
OG00113
Title
Denominators
Categories
Title
Measurements
OG000200
OG001200
Primary
Time to Progression (TTP) in Phase II
TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.
Treated set, only phase II participants.
Posted
Median
Inter-Quartile Range
months
From randomization until data cut-off (15 July 2014); Up to 1031 days
ID
Title
Description
OG000
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
OG001
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macro-vascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Secondary
Incidence of Dose Limiting Toxicity in Phase I
Number of patients with dose limiting toxicity are presented
Treated set (Phase I patients from the dose escalation part that were not replaced for MTD determination).
Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD).
Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST (aspartate aminotransferase ) and ALT (alanine transaminase) ≤2 times the upper limit of normal (ULN).
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
OG002
Phase I Group 1, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid).
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Secondary
Objective Tumour Response by RECIST
Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.
95% Confidence Interval presented below are computed by Clopper and Pearson method.
Treated set, phase II participants only
Posted
Number
95% Confidence Interval
percentage of participants
From randomization until data cut-off (15 July 2014); Up to 1031 days
ID
Title
Description
OG000
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
OG001
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macro-vascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Secondary
Progression Free Survival (PFS)
PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.
Treated set, only phase II participants
Posted
Median
Inter-Quartile Range
months
From randomization until data cut-off (15 July 2014); Up to 1031 days
ID
Title
Description
OG000
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
OG001
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macro-vascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Secondary
Overall Survival
Overall survival was defined as the duration from date of randomisation to the date of death.
Treated set, only phase II participants
Posted
Median
Inter-Quartile Range
months
From randomization until data cut-off (15 July 2014); Up to 1031 days
ID
Title
Description
OG000
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
OG001
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macro-vascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Units
Counts
Time Frame
From first administration of the trial drug and until 28 days after the last administration of nintedanib or sorafenib, up to 1289 days
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Phase 1 Group 1, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD). Group 1 patients had a baseline Child-Pugh score of 5 or 6, and aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤2 times the upper limit of normal (ULN).
3
6
6
6
EG001
Phase I Group 1, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
1
3
3
3
EG002
Phase I Group 1, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
4
4
4
4
EG003
Phase I Group 2, 50mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 50 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
3
3
3
3
EG004
Phase I Group 2, 100mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
2
4
4
4
EG005
Phase I Group 2, 150mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
3
4
4
4
EG006
Phase I Group 2, 200mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
4
8
7
8
EG007
Phase II, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
34
62
61
62
EG008
Phase II, 400 mg Sorafenib Bid
Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
14
31
31
31
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG0030 affected3 at risk
EG0040 affected4 at risk
EG0051 affected4 at risk
EG0060 affected8 at risk
EG0073 affected62 at risk
EG0081 affected31 at risk
Splenic vein thrombosis
Blood and lymphatic system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Acute coronary syndrome
Cardiac disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Glaucoma
Eye disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Macular fibrosis
Eye disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Retinal detachment
Eye disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastric varices haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oesophageal food impaction
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oesophageal varices haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Varices oesophageal
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Chest pain
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Disease progression
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fatigue
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
General physical health deterioration
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Impaired healing
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Multi-organ failure
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Performance status decreased
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bile duct obstruction
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatic pain
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Biliary sepsis
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hepatitis B
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Ludwig angina
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Peritonitis bacterial
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Postoperative wound infection
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sepsis
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Concussion
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lipase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Diabetes mellitus inadequate control
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatocellular carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Metastatic neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tumour thrombosis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Depressed level of consciousness
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatic encephalopathy
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nephrotic syndrome
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperventilation
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Respiratory alkalosis
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Stevens-Johnson syndrome
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatectomy
Surgical and medical procedures
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bleeding varicose vein
Vascular disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG0030 affected3 at risk
EG0040 affected4 at risk
EG0050 affected4 at risk
EG0060 affected8 at risk
EG0075 affected62 at risk
EG0081 affected31 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cerumen impaction
Ear and labyrinth disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Deafness
Ear and labyrinth disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Eye discharge
Eye disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0023 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0003 affected6 at risk
EG0011 affected3 at risk
EG0022 affected4 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected3 at risk
EG0022 affected4 at risk
EG003
Abdominal tenderness
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Anorectal varices
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0002 affected6 at risk
EG0012 affected3 at risk
EG0023 affected4 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Duodenal ulcer
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0012 affected3 at risk
EG0020 affected4 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0013 affected3 at risk
EG0023 affected4 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tooth loss
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 17.0
Systematic Assessment
EG0002 affected6 at risk
EG0013 affected3 at risk
EG0023 affected4 at risk
EG003
Asthenia
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Catheter site bruise
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Chest pain
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Chills
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Device difficult to use
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fatigue
General disorders
MedDRA 17.0
Systematic Assessment
EG0003 affected6 at risk
EG0010 affected3 at risk
EG0023 affected4 at risk
EG003
Feeling cold
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Gait disturbance
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
General physical health deterioration
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Impaired healing
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Inflammation
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Influenza like illness
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected3 at risk
EG0023 affected4 at risk
EG003
Injection site bruising
General disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Local swelling
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Malaise
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oedema
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oedema peripheral
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pain
General disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 17.0
Systematic Assessment
EG0002 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hepatic haemorrhage
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hepatic pain
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Portal vein thrombosis
Hepatobiliary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Influenza
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Contrast media reaction
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Tooth fracture
Injury, poisoning and procedural complications
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Amylase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected3 at risk
EG0020 affected4 at risk
EG003
Blood albumin decreased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected3 at risk
EG0020 affected4 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0002 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Blood potassium decreased
Investigations
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood thyroid stimulating hormone increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lipase increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Liver function test abnormal
Investigations
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Platelet count decreased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Transaminases increased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Weight decreased
Investigations
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0023 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pain in jaw
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Pathological fracture
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Aphonia
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dizziness postural
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Dyskinesia
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Encephalopathy
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Headache
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sensory disturbance
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sensory loss
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Syncope
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tremor
Nervous system disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Depressed mood
Psychiatric disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected3 at risk
EG0020 affected4 at risk
EG003
Chromaturia
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Oliguria
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Renal failure acute
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Increased viscosity of bronchial secretion
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperkeratosis
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Palmar-plantar erythrodysaesthesia syndrome
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Skin reaction
Skin and subcutaneous tissue disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypertension
Vascular disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hypotension
Vascular disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Intra-abdominal haematoma
Vascular disorders
MedDRA 17.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Boehringer Ingelheim Call Center
Boehringer Ingelheim
1-800-243-0127
clintriage.rdg@boehringer-ingelheim.com
ID
Term
D006528
Carcinoma, Hepatocellular
Ancestor Terms
ID
Term
D000230
Adenocarcinoma
D002277
Carcinoma
D009375
Neoplasms, Glandular and Epithelial
D009370
Neoplasms by Histologic Type
D009369
Neoplasms
D008113
Liver Neoplasms
D004067
Digestive System Neoplasms
D009371
Neoplasms by Site
D004066
Digestive System Diseases
D008107
Liver Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000077157
Sorafenib
C530716
nintedanib
Ancestor Terms
ID
Term
D010671
Phenylurea Compounds
D014508
Urea
D000577
Amides
D009930
Organic Chemicals
D001555
Benzene Derivatives
D006841
Hydrocarbons, Aromatic
D006844
Hydrocarbons, Cyclic
D006838
Hydrocarbons
D009536
Niacinamide
D009539
Nicotinic Acids
D000147
Acids, Heterocyclic
D006571
Heterocyclic Compounds
D011725
Pyridines
D006573
Heterocyclic Compounds, 1-Ring
Browse Leaves
Not provided
Browse Branches
Not provided
2 subjects
FG0052 subjects
FG0067 subjects
FG00721 subjects
FG0086 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0082 subjects
0 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
72.3
± 11.7
BG00456.3± 6.4
BG00559.3± 13.9
BG00657.0± 11.0
BG00765.4± 10.0
BG00863.1± 11.8
BG00964.2± 10.5
0
BG0030
BG0040
BG0051
BG0062
BG00714
BG0085
BG00924
Male
BG0005
BG0012
BG0024
BG0033
BG0044
BG0053
BG0066
BG00748
BG00826
BG009101
Units
Counts
Participants
OG00062
OG00131
Title
Denominators
Categories
Title
Measurements
OG0005.45(2.69 to 9.20)
OG0014.63(2.79 to 20.40)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
1.437
2-Sided
95
0.805
2.565
Hazard ratio (HR) from Cox proportional hazards model stratified by macroscopic vacular invasion, extrahepatic spread, or both present vs both absent.
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
OG006
Phase I Group 2, 200 mg Nintedanib Bid
Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg)twice daily (bid).
Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0033
OG0044
OG0053
OG0063
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
Units
Counts
Participants
OG00062
OG00131
Title
Denominators
Categories
Title
Measurements
OG0001.6(0.0 to 8.7)
OG0016.5(0.8 to 21.4)
Units
Counts
Participants
OG00062
OG00131
Title
Denominators
Categories
Title
Measurements
OG0005.32(2.69 to 9.20)
OG0013.94(2.33 to 7.36)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
1.351
2-Sided
95
0.779
2.343
Hazard ratio from Cox proportional hazards model stratified by macroscopic vacular invasion, extrahepatic spread, or both present vs both absent.
HR below 1 favors Nintedanib.
Superiority or Other
Participants
OG00062
OG00131
Title
Denominators
Categories
Title
Measurements
OG00011.86(6.60 to 25.46)
OG00111.40(6.51 to 17.25)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
0.877
2-Sided
95
0.522
1.473
Hazard ratio from Cox proportional hazards model stratified by macroscopic vacular invasion, extrahepatic spread, or both present vs both absent.