BIBW 2992 (Afatinib) With or Without Daily Temozolomide i... | NCT00727506 | Trialant
NCT00727506
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Aug 15, 2017Actual
Enrollment
151Actual
Phase
Phase 2
Conditions
Glioma
Interventions
BIBW 2992
TMZ
BIBW 2992 plus TMZ
Countries
United States
Canada
Protocol Section
Identification Module
NCT ID
NCT00727506
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1200.36
Secondary IDs
Not provided
Brief Title
BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma
Official Title
Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Jul 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
Jul 14, 2008Actual
Primary Completion Date
May 12, 2011Actual
Completion Date
May 25, 2016Actual
First Submitted Date
Jul 31, 2008
First Submission Date that Met QC Criteria
Aug 1, 2008
First Posted Date
Aug 4, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 8, 2013
Results First Submitted that Met QC Criteria
Jan 2, 2014
Results First Posted Date
Jan 24, 2014Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jul 10, 2017
Last Update Posted Date
Aug 15, 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
Phase I Part: To determine the maximum tolerated dose (MTD) and pharmacokinetics of BIBW 2992 administered in combination with TMZ in patients with recurrent malignant gliomas (WHO Grade III and IV).
Phase II Part: To estimate the efficacy and safety of BIBW 2992 monotherapy and BIBW 2992 / TMZ combination therapy compared to TMZ monotherapy (three treatment arms) in patients with recurrent GBM. To evaluate molecular determinants of response to BIBW 2992.
Detailed Description
Not provided
Conditions Module
Conditions
Glioma
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
151Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
BIBW 2992
Experimental
BIBW 2992 once daily
Drug: BIBW 2992
TMZ
Active Comparator
TMZ 21/28 days
Drug: TMZ
BIBW 2992 plus TMZ
Experimental
BIBW 2992 once daily plus TMZ 21/28 days
Drug: BIBW 2992 plus TMZ
Interventions
Name
Type
Description
Arm Group Labels
Other Names
BIBW 2992
Drug
BIBW 2992 once daily
BIBW 2992
TMZ
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With DLT- Phase I
Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days
Progression-free Survival (PFS-6) at Six Months - Phase II
PFS-6 is defined as probability of patients surviving to six months after randomization without progression. Disease progression was evaluated by an independent review committee and by the investigators, independently. The evaluation by the independent review committee was used for the primary outcome measure. The measurement "Number" the estimated PFS-6 value from the Kaplan-Meier curve of PFS.
At six months after randomization
Secondary Outcomes
Measure
Description
Time Frame
Objective Tumor Response in Phase I
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.
From treatment start until the date of first documented progression or data cutoff at May 12, 2011, whichever came first, with a mean treatment duration of 69.7 days.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Phase I Part:
Histologically-confirmed WHO Grade III or IV malignant glioma that is recurrent after prior chemoradiotherapy. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Grade III or IV malignant glioma.
Age at least 18 years at entry
KPS at least 60%
Patients must have recovered from previous surgery and chemotherapy.
Written informed consent that is consistent with local law and ICH-GCP guidelines.
Phase II Part:
Histologically-confirmed WHO Grade IV malignant glioma at first episode of recurrence after prior combined chemoradiotherapy. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Grade IV malignant glioma and if prior treatment included temozolomide chemotherapy and radiotherapy.
Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on Gd MRI performed within 14 days prior to first treatment (Day 1).
Age at least 18 years at entry
KPS at least 70%
Patients must have recovered from previous surgery and chemotherapy.
Written informed consent that is consistent with local law and ICH-GCP guidelines.
Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of study treatment.
Exclusion criteria:
Phase I and Phase II Parts:
Less than 12 weeks between radiotherapy and start of study treatment, unless new enhancing lesion outside of radiation field or radiologically progressive on two consecutive MRI scans at least four weeks apart or biopsy-proven recurrence.
Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.
Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.
Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide dosing (defined as temozolomide administered more than 5 days/28 day cycle).
Active infectious disease requiring intravenous therapy.
Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
Patient is <3 years free of another primary malignancy except: if the other primary malignancy is either not currently clinically significant or does not require active intervention (such as a basal cell skin cancer or a cervical carcinoma in situ). Existence of any other malignant disease is not allowed.
Cardiac left ventricular function with resting ejection fraction <50%.
Absolute neutrophil count (ANC) less than 1500/mm3.
Platelet count less than 100,000/mm3.
Bilirubin greater than 1.5 x upper limit of institutional norm.
Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm.
Serum creatinine greater than 1.5 x upper limit of institutional norm.
Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
Pregnancy or breast-feeding.
Patients unable to comply with the protocol.
Known pre-existing interstitial lung disease (ILD).
Phase I part only:
1. Less than four weeks from prior treatment with bevacizumab.
Phase II Part only:
Prior EGFR-directed therapy.
Prior bevacizumab therapy.
Patients presenting with second or higher number of episodes of recurrence.
Requirement of treatment with any of the prohibited concomitant medications listed in Section 4.2.2 (Restrictions regarding concomitant treatment).
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
1200.36.0016 Boehringer Ingelheim Investigational Site
Birmingham
Alabama
United States
1200.36.0012 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
This study consists of 2 parts (phase I and phase II) with separate participants.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
FG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
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
Not provided
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
TMZ 21/28
TMZ
BIBW 2992 plus TMZ
Drug
BIBW 2992 once daily plus TMZ 21/28 days
BIBW 2992 plus TMZ
Objective Tumor Response in Phase II
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review. Only data collected until cut-off date July 15, 2016 were considered.
From randomization to until the date of first documented progression or data cutoff on July 15, 2016, whichever came first, with a mean treatment duration of 110.0 days
Progression-free Survival (PFS)- Phase II Part
Progression-free survival was defined as the duration between randomization and the date of the first of the two following events: progression or death.
from date of randomization until the date of first documented progression or death by any cause, whichever came first, assessed up to 9 Months.
AUCÏ„,ss for Afatinib
Area under the plasma concentration-time curve of afatinib after multiple administration (AUCτ,ss) of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide (TMZ).
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24 h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Cmax,ss for Afatinib
maximum measured plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide.
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Tmax,ss for Afatinib
time from dosing to the maximum plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
AUC (0-8) for Temozolomide
Area under the plasma concentration-time curve over the time interval from zero to 08h (AUC (0-8)) of temozolomide in presence and absence of afatinib.
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Cmax for Temozolomide
maximum measured plasma concentration following the first dose of uniform intervals Ï„ (Cmax) of temozolomide in presence and absence of afatinib.
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Tmax for Temozolomide
time from dosing to the maximum plasma concentration following the first dose of uniform intervals Ï„ (tmax) of temozolomide in presence and absence of afatinib.
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
t1/2 for Temozolomide
terminal half-life (t1/2) of temozolomide in presence and absence of afatinib
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Phase II - Trough Plasma Concentration of Afatinib
Trough plasma concentration of afatinib after multiple administration of 40 mg afatinib administered as monotherapy or in combination with 75 mg/m² temozolomide
Before (-0.05 h) the drug administration of afatinib on Day 15 of Cycle 2 & 3
Number of Participants With EGFRvIII Assessed by IHC Test.
Number of participants with the epidermal growth factor receptor variant III (EGFRvIII) assessed by IHC test for the evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFRvIII by immunohistochemistry (IHC) test.
Baseline (during screening)
Number of Participants With MGMT Marker Assessed by IHC Test.
Number of participants with MGMT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for O6-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry (IHC) test.
Baseline (during screening)
Number of Participants With EGFR Marker Assessed by IHC Test.
Number of participants with EGFR marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (IHC) test
Baseline (during screening)
Number of Participants With PTEN Marker Assessed by IHC Test.
Number of participants with PTEN marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Phosphatase and Tensin Homologue - a tumor suppressor gene/protein (PTEN) by immunohistochemistry (IHC) test.
Baseline (during screening)
Number of Participants With PAKT Marker Assessed by IHC Test.
Number of participants with PAKT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Serinethreonine kinase (PAKT) by immunohistochemistry (IHC) test.
Baseline (during screening)
Number of Participants With EGFR Assessed by FISH
Number of participants with EGFR assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFR by fluorescent in situ hybridization (FISH).
Baseline (during screening)
Number of Participants With PTEN Assessed by FISH
Number of participants with PTEN assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for PTEN by fluorescent in situ hybridization (FISH).
Baseline (during screening)
Number of Participants With Chromosomes (CEP7) Assessed by FISH
Number of participants with Chromosomes (CEP7) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP7) by fluorescent in situ hybridization (FISH).
Baseline (during screening)
Number of Participants With Chromosomes (CEP10) Assessed by FISH
Number of participants with Chromosomes (CEP10) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP10) by fluorescent in situ hybridization (FISH).
Baseline (during screening)
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
Safety was assessed based on number of participants with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, All Serious Adverse events (AE) and other significant AEs (according to International Conference on Harmonisation (ICH) E3).
From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological
From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Safety of Afatinib assesed based on Number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
From first administration of treatment until 28 days after last drug administration, up to 491 days.
Causes of Death - Phase I
Cause of the death reported during on treatment was due to disease progression.
From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
Safety was assessed based on number of participants with investigator defined drug-related AEs, AE leading to dose reduction, Adverse events (AEs) leading to discontinuation of trial drug and All Serious Adverse events (SAE).
From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological.
From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Safety of Afatinib assessed based on the number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
From first administration of treatment until 28 days after last drug administration, up to 518 days.
Causes of Death - Phase II
Causes of death during on treatment.
From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Clinically Relevant Abnormalities for Decreased Cardiac Left Ventricular Function - Phase II
Number of participants with Clinically Relevant Abnormalities for decreased Cardiac left ventricular function.
From first administration of treatment until 28 days after last drug administration, up to 518 days.
Phoenix
Arizona
United States
1200.36.0005 Boehringer Ingelheim Investigational Site
Duarte
California
United States
1200.36.0014 Boehringer Ingelheim Investigational Site
Los Angeles
California
United States
1200.36.0019 Boehringer Ingelheim Investigational Site
Orlando
Florida
United States
1200.36.0023 Boehringer Ingelheim Investigational Site
Atlanta
Georgia
United States
1200.36.0008 Boehringer Ingelheim Investigational Site
Louisville
Kentucky
United States
1200.36.0002 Boehringer Ingelheim Investigational Site
Boston
Massachusetts
United States
1200.36.0003 Boehringer Ingelheim Investigational Site
Detroit
Michigan
United States
1200.36.0009 Boehringer Ingelheim Investigational Site
New York
New York
United States
1200.36.0001 Boehringer Ingelheim Investigational Site
Durham
North Carolina
United States
1200.36.0007 Boehringer Ingelheim Investigational Site
Charleston
South Carolina
United States
1200.36.0020 Boehringer Ingelheim Investigational Site
Memphis
Tennessee
United States
1200.36.0017 Boehringer Ingelheim Investigational Site
Dallas
Texas
United States
1200.36.0010 Boehringer Ingelheim Investigational Site
Houston
Texas
United States
1200.36.0011 Boehringer Ingelheim Investigational Site
Charlottesville
Virginia
United States
1200.36.0022 Boehringer Ingelheim Investigational Site
Seattle
Washington
United States
1200.36.1005 Boehringer Ingelheim Investigational Site
Calgary
Alberta
Canada
1200.36.1010 Boehringer Ingelheim Investigational Site
Winnipeg
Manitoba
Canada
1200.36.1009 Boehringer Ingelheim Investigational Site
Moncton
New Brunswick
Canada
1200.36.1011 Boehringer Ingelheim Investigational Site
Halifax
Nova Scotia
Canada
1200.36.1008 Boehringer Ingelheim Investigational Site
Hamilton
Ontario
Canada
1200.36.1001 Boehringer Ingelheim Investigational Site
Kingston
Ontario
Canada
1200.36.1003 Boehringer Ingelheim Investigational Site
Toronto
Ontario
Canada
1200.36.1004 Boehringer Ingelheim Investigational Site
Toronto
Ontario
Canada
1200.36.1007 Boehringer Ingelheim Investigational Site
Fleurimont
Quebec
Canada
1200.36.1002 Boehringer Ingelheim Investigational Site
Montreal
Quebec
Canada
1200.36.1006 Boehringer Ingelheim Investigational Site
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
FG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
FG003
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
FG004
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
FG005
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
FG0006 subjectsEntered
FG0018 subjectsEntered
FG00218 subjectsEntered
FG00339 subjectsRandomized
FG00441 subjectsRandomized
FG00539 subjectsRandomized
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0006 subjects
FG0018 subjects
FG00218 subjects
FG00339 subjects
FG00441 subjects
FG00539 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0024 subjects
FG0034 subjects
FG0041 subjects
FG0058 subjects
Dose Limiting Toxicity (DLT)
FG0002 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Progressive disease
FG0004 subjects
FG0017 subjects
FG0029 subjects
FG00328 subjects
FG004
Refused to continue medication
FG0000 subjects
FG0011 subjects
FG0022 subjects
FG0033 subjects
FG004
Other reason not described above
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0034 subjects
FG004
For Phase I part, all patients who were treated with at least one dose of the study medication. For Phase II part, all patients who were randomized and have taken at least one dose of the study medication.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
BG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
BG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
BG003
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
BG004
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
BG005
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0018
BG00218
BG00339
BG00441
BG00539
BG006151
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
BG00051.7± 12.4
BG00151.6± 14.2
BG00251.0± 9.4
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0012
BG002
Race/Ethnicity, Customized
Number
Number of participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0000
BG0011
BG002
Karnofsky performance score
The scale range is from 100 (Normal no complaints) to 0 (dead). This score was used in Phase II randomization stratification and in some efficacy analyses.
Number
Number of participants
Title
Denominators
Categories
70
Title
Measurements
BG0001
BG0011
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
Number of Participants With DLT- Phase I
Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
Posted
Number
participants
From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Units
Counts
Participants
OG0006
OG0018
OG00218
Title
Denominators
Categories
Title
Measurements
OG0002
OG0010
OG0024
Primary
Progression-free Survival (PFS-6) at Six Months - Phase II
PFS-6 is defined as probability of patients surviving to six months after randomization without progression. Disease progression was evaluated by an independent review committee and by the investigators, independently. The evaluation by the independent review committee was used for the primary outcome measure. The measurement "Number" the estimated PFS-6 value from the Kaplan-Meier curve of PFS.
Randomised Set (RS). The randomised set includes all patients who were randomised to receive treatment in the Phase II part of the trial.
Posted
Number
95% Confidence Interval
probablity of survival
At six months after randomization
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Secondary
Objective Tumor Response in Phase I
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.
Patients treated in Phase I part
Posted
Number
participants
From treatment start until the date of first documented progression or data cutoff at May 12, 2011, whichever came first, with a mean treatment duration of 69.7 days.
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Secondary
Objective Tumor Response in Phase II
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review. Only data collected until cut-off date July 15, 2016 were considered.
RS
Posted
Number
participants
From randomization to until the date of first documented progression or data cutoff on July 15, 2016, whichever came first, with a mean treatment duration of 110.0 days
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Secondary
Progression-free Survival (PFS)- Phase II Part
Progression-free survival was defined as the duration between randomization and the date of the first of the two following events: progression or death.
Randomized set
Posted
Median
Full Range
Months
from date of randomization until the date of first documented progression or death by any cause, whichever came first, assessed up to 9 Months.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
AUCÏ„,ss for Afatinib
Area under the plasma concentration-time curve of afatinib after multiple administration (AUCτ,ss) of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide (TMZ).
PKS Set and the patients who had enough PK samples for calculation of AUC. Pharmacokinetic set (PKS) : All patients who provided at least one blood sample were included in the Pharmacokinetic (PK) analysis.
Posted
Geometric Mean
Standard Deviation
ng·h/mL
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24 h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of temozolomide).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of temozolomide).
Units
Counts
Secondary
Cmax,ss for Afatinib
maximum measured plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide.
PKS set
Posted
Geometric Mean
Standard Deviation
ng/mL
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of temozolomide).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of temozolomide).
Units
Counts
Participants
Secondary
Tmax,ss for Afatinib
time from dosing to the maximum plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide
PKS set
Posted
Median
Full Range
hour
Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of temozolomide).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of TMZ)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of temozolomide).
Units
Counts
Participants
Secondary
AUC (0-8) for Temozolomide
Area under the plasma concentration-time curve over the time interval from zero to 08h (AUC (0-8)) of temozolomide in presence and absence of afatinib.
PKS set
Posted
Geometric Mean
Geometric Coefficient of Variation
ng·h/mL
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of Afatinib).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of Afatinib).
Units
Counts
Participants
Secondary
Cmax for Temozolomide
maximum measured plasma concentration following the first dose of uniform intervals Ï„ (Cmax) of temozolomide in presence and absence of afatinib.
PKS set
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of Afatinib).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of Afatinib).
Units
Counts
Participants
Secondary
Tmax for Temozolomide
time from dosing to the maximum plasma concentration following the first dose of uniform intervals Ï„ (tmax) of temozolomide in presence and absence of afatinib.
PKS set
Posted
Median
Full Range
h
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of Afatinib).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of Afatinib).
Units
Counts
Participants
Secondary
t1/2 for Temozolomide
terminal half-life (t1/2) of temozolomide in presence and absence of afatinib
PKS set
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
ID
Title
Description
OG000
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Presence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in presence of Afatinib).
OG001
Phase I - Afatinib 50mg+TMZ 75mg/m^2 (in Absence of Afatinib)
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part (in absence of Afatinib).
Units
Counts
Participants
OG000
Secondary
Phase II - Trough Plasma Concentration of Afatinib
Trough plasma concentration of afatinib after multiple administration of 40 mg afatinib administered as monotherapy or in combination with 75 mg/m² temozolomide
PKS
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Before (-0.05 h) the drug administration of afatinib on Day 15 of Cycle 2 & 3
ID
Title
Description
OG000
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG001
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Participants
OG000
Secondary
Number of Participants With EGFRvIII Assessed by IHC Test.
Number of participants with the epidermal growth factor receptor variant III (EGFRvIII) assessed by IHC test for the evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFRvIII by immunohistochemistry (IHC) test.
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With MGMT Marker Assessed by IHC Test.
Number of participants with MGMT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for O6-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry (IHC) test.
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With EGFR Marker Assessed by IHC Test.
Number of participants with EGFR marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (IHC) test
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With PTEN Marker Assessed by IHC Test.
Number of participants with PTEN marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Phosphatase and Tensin Homologue - a tumor suppressor gene/protein (PTEN) by immunohistochemistry (IHC) test.
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Secondary
Number of Participants With PAKT Marker Assessed by IHC Test.
Number of participants with PAKT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Serinethreonine kinase (PAKT) by immunohistochemistry (IHC) test.
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With EGFR Assessed by FISH
Number of participants with EGFR assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFR by fluorescent in situ hybridization (FISH).
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Participants
Secondary
Number of Participants With PTEN Assessed by FISH
Number of participants with PTEN assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for PTEN by fluorescent in situ hybridization (FISH).
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Participants
Secondary
Number of Participants With Chromosomes (CEP7) Assessed by FISH
Number of participants with Chromosomes (CEP7) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP7) by fluorescent in situ hybridization (FISH).
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With Chromosomes (CEP10) Assessed by FISH
Number of participants with Chromosomes (CEP10) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP10) by fluorescent in situ hybridization (FISH).
Randomized set
Posted
Number
Participants
Baseline (during screening)
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Secondary
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
Safety was assessed based on number of participants with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, All Serious Adverse events (AE) and other significant AEs (according to International Conference on Harmonisation (ICH) E3).
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 491 days.
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Secondary
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 491 days.
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Secondary
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Safety of Afatinib assesed based on Number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 491 days.
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Secondary
Causes of Death - Phase I
Cause of the death reported during on treatment was due to disease progression.
Treated set
Posted
Number
deaths
From first administration of treatment until 28 days after last drug administration, up to 491 days.
ID
Title
Description
OG000
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
OG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
Units
Counts
Participants
Secondary
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
Safety was assessed based on number of participants with investigator defined drug-related AEs, AE leading to dose reduction, Adverse events (AEs) leading to discontinuation of trial drug and All Serious Adverse events (SAE).
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 518 days.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Secondary
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological.
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 518 days.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Secondary
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Safety of Afatinib assessed based on the number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 518 days.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Secondary
Causes of Death - Phase II
Causes of death during on treatment.
Treated set
Posted
Number
deaths
From first administration of treatment until 28 days after last drug administration, up to 518 days.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Participants
Secondary
Number of Participants With Clinically Relevant Abnormalities for Decreased Cardiac Left Ventricular Function - Phase II
Number of participants with Clinically Relevant Abnormalities for decreased Cardiac left ventricular function.
Treated set
Posted
Number
Participants
From first administration of treatment until 28 days after last drug administration, up to 518 days.
ID
Title
Description
OG000
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
OG001
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
OG002
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
Units
Counts
Time Frame
From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
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 I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
2
6
6
6
EG001
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
1
8
8
8
EG002
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase I part
10
18
18
18
EG003
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m^2 for 21 days followed by 7 days off - Phase II part
6
39
36
39
EG004
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
10
41
40
41
EG005
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m^2 for 21 days followed by 7 days off - Phase II part.
13
39
37
39
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG0030 affected39 at risk
EG0041 affected41 at risk
EG0050 affected39 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Spontaneous haematoma
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Necrotising fasciitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Sepsis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Altered state of consciousness
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Headache
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Hemiparesis
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Hydrocephalus
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Neurological decompensation
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Acute prerenal failure
Renal and urinary disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
General physical health deterioration
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Seizure
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Disease progression
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Influenza like illness
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Aphasia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0022 affected18 at risk
EG003
Grand mal convulsion
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Paralysis
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Delirium
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Thrombosis
Vascular disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphopenia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG0035 affected39 at risk
EG0040 affected41 at risk
EG0050 affected39 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Deafness bilateral
Ear and labyrinth disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dry eye
Eye disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Eye pain
Eye disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Vision blurred
Eye disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0002 affected6 at risk
EG0010 affected8 at risk
EG0024 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0014 affected8 at risk
EG00213 affected18 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected8 at risk
EG0022 affected18 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected8 at risk
EG0027 affected18 at risk
EG003
Infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Localised infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Paronychia
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Rash pustular
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0012 affected8 at risk
EG0020 affected18 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Weight decreased
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Weight increased
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0023 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0025 affected18 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected8 at risk
EG0027 affected18 at risk
EG003
Increased appetite
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0023 affected18 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Amnesia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Aphasia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cognitive disorder
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0023 affected18 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Headache
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0002 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Hemiparesis
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Motor dysfunction
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Speech disorder
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Tremor
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0021 affected18 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected8 at risk
EG0022 affected18 at risk
EG003
Depression
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0022 affected18 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Panic attack
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0012 affected8 at risk
EG0023 affected18 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0017 affected8 at risk
EG00213 affected18 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0023 affected18 at risk
EG003
Chills
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0012 affected8 at risk
EG0029 affected18 at risk
EG003
Gait disturbance
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oedema peripheral
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Temperature intolerance
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Influenza
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Malignant neoplasm progression
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Seizure
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Sensory disturbance
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Ingrowing nail
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Dyschezia
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oral discomfort
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Tongue discolouration
Gastrointestinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Feeling cold
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Irritability
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Malaise
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oedema
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Pain
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Thirst
General disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Candidiasis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Rhinovirus infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Vaginal infection
Infections and infestations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Toxicity to various agents
Injury, poisoning and procedural complications
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Electrocardiogram abnormal
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Lipase increased
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Liver function test abnormal
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
White blood cells urine
Investigations
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Myopathy
Musculoskeletal and connective tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Ataxia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0021 affected18 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0002 affected6 at risk
EG0011 affected8 at risk
EG0023 affected18 at risk
EG003
Hemianopia
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Mental impairment
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Partial seizures
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Peroneal nerve palsy
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Sedation
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Syncope
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0020 affected18 at risk
EG003
Vasogenic cerebral oedema
Nervous system disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Affect lability
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Genital discomfort
Reproductive system and breast disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Vulvovaginal discomfort
Reproductive system and breast disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0001 affected6 at risk
EG0010 affected8 at risk
EG0020 affected18 at risk
EG003
Pruritus generalised
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Rash generalised
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0022 affected18 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected8 at risk
EG0021 affected18 at risk
EG003
Hypotension
Vascular disorders
MedDRA 14.0 and 19.0
Systematic Assessment
EG0000 affected6 at risk
EG0011 affected8 at risk
EG0021 affected18 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
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
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
D005910
Glioma
Ancestor Terms
ID
Term
D018302
Neoplasms, Neuroepithelial
D017599
Neuroectodermal Tumors
D009373
Neoplasms, Germ Cell and Embryonal
D009370
Neoplasms by Histologic Type
D009369
Neoplasms
D009375
Neoplasms, Glandular and Epithelial
D009380
Neoplasms, Nerve Tissue
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000077716
Afatinib
D000077204
Temozolomide
Ancestor Terms
ID
Term
D000577
Amides
D009930
Organic Chemicals
D011799
Quinazolines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D006571
Heterocyclic Compounds
D003606
Dacarbazine
D014226
Triazenes
D007093
Imidazoles
D001393
Azoles
D006573
Heterocyclic Compounds, 1-Ring
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
38 subjects
FG00528 subjects
1 subjects
FG0052 subjects
1 subjects
FG0051 subjects
56.9
± 10.62
BG00456.6± 9.44
BG00555.4± 11.02
BG00656.3± 10.3
8
BG00314
BG00414
BG00518
BG00658
Male
BG0004
BG0016
BG00210
BG00325
BG00427
BG00521
BG00693
0
BG0030
BG0041
BG0051
BG0063
Black/African American
Title
Measurements
BG0000
BG0010
BG0022
BG0032
BG0040
BG0052
BG0066
Hawaiian/Pacific Isle
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0051
BG0061
White
Title
Measurements
BG0006
BG0017
BG00216
BG00337
BG00440
BG00535
BG006141
BG0021
BG0039
BG0049
BG00512
BG00633
80
Title
Measurements
BG0001
BG0011
BG0022
BG00313
BG00412
BG0059
BG00638
90
Title
Measurements
BG0002
BG0014
BG00211
BG00312
BG00417
BG00515
BG00661
100
Title
Measurements
BG0002
BG0012
BG0024
BG0035
BG0043
BG0053
BG00619
Units
Counts
Participants
OG00039
OG00141
OG00239
Title
Denominators
Categories
Title
Measurements
OG0000.230(0.09 to 0.37)
OG0010.030(0.00 to 0.09)
OG0020.103(0.00 to 0.21)
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
OG002
z-test
0.148
P-value is from an approximate normal test for the 6 month time point.
95
Superiority or Other
OG000
OG001
z-test
0.008
P-value is an approximate normal test for the six month time point.
95
Superiority or Other
Units
Counts
Participants
OG0006
OG0018
OG00218
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
Units
Counts
Participants
OG00039
OG00141
OG00239
Title
Denominators
Categories
Title
Measurements
OG0004(2.9 to 24.2)
OG0011(0.1 to 12.9)
OG0023(1.6 to 20.9)
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
OG002
Fisher Exact
1.0000
95
Superiority or Other
OG000
OG001
Fisher Exact
0.1954
95
Superiority or Other
Participants
OG00039
OG00141
OG00239
Title
Denominators
Categories
Title
Measurements
OG0001.87(1.15 to 3.68)
OG0010.99(0.95 to 1.84)
OG0021.53(0.99 to 1.87)
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 was calculated from Cox proportional hazard model stratified by age class (<=50 vs. >50 years old) and baseline Karnofsky Performance Scale (KPS) score (70, 80 vs. 90, 100). P-value was two-sided from log-rank test stratified by the same variables.
Log Rank
0.0320
Cox Proportional Hazard
1.780
2-Sided
95
1.088
2.912
Superiority or Other
OG000
OG002
Hazard ratio was calculated from Cox proportional hazard model stratified by age class (<=50 vs. >50 years old) and baseline KPS score (70, 80 vs. 90, 100). P-value was two-sided from log-rank test stratified by the same variables.