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LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

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ClinicalTrials.gov Identifier: NCT01085136
Recruitment Status : Completed
First Posted : March 11, 2010
Results First Posted : October 3, 2014
Last Update Posted : April 4, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: Investigator´s choice of chemotherapy
Drug: BIBW 2992
Enrollment 1154
Recruitment Details  
Pre-assignment Details PD = Progression Disease
Arm/Group Title Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme). Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics). Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Period Title: Part A
Started 1154 0 [1] 0
Randomized to Part B 206 [2] 0 0
Completed 831 [3] 0 0
Not Completed 323 0 0
Reason Not Completed
Other Adverse event             223             0             0
Protocol Violation             3             0             0
Lost to Follow-up             3             0             0
Refusal to continue trial medication             64             0             0
Other reason not defined above             30             0             0
[1]
Only Afatinib monotherapy administered in Part A
[2]
Discontinued Part A -Randomized to Part B
[3]
Randomized to Part B & completed trial as per protocol, had PD, clinical progression.
Period Title: Part B
Started 0 [1] 138 68
Completed 0 [1] 87 [2] 42 [2]
Not Completed 0 51 26
Reason Not Completed
Other AE             0             29             8
Refusal to continue trial medication             0             12             7
Not treated             0             4             8
Other reason not defined above             0             6             3
[1]
Afatinib monotherapy not administered in Part B
[2]
Completed trial as per protocol, had progressive disease, clinical signs or symptoms of progression
Arm/Group Title Afatinib Monotherapy (Part A)
Hide Arm/Group Description Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
Overall Number of Baseline Participants 1154
Hide Baseline Analysis Population Description
Treated set, i.e. all patients who were documented to have taken at least 1 dose of afatinib 50 mg in Part A of the trial and all patients who received at least 1 dose of trial medication in Part B.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1154 participants
<=18 years
0
   0.0%
Between 18 and 65 years
741
  64.2%
>=65 years
413
  35.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1154 participants
60.1  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1154 participants
Female
654
  56.7%
Male
500
  43.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1154 participants
Eastern Asian 491
Caucasian 459
Other 29
Unknown 175
Baseline Eastern Cooperative Oncology Group (ECOG) performance score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1154 participants
0 341
1 691
2 122
[1]
Measure Description: Subjects were graded based on following ECOG PS grade criteria: Grade 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory & able to carry out work of a light nature. Grade 2: Ambulatory & capable of all selfcare but unable to carry out any work activities. Up & about more than 50% of waking hours. Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. Grade 4: Completely disabled. Totally confined to bed or chair. Grade 5: Dead.
Smoking history  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1154 participants
Never smoked 615
<15 pack years & stopped >1 year before diagnosis 132
Other current or ex−smoker 407
Histologic classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1154 participants
Adenocarcinoma 985
Squamous 90
Other 78
Missing 1
1.Primary Outcome
Title Progression Free Survival (Part B)
Hide Description

Progression free survival (PFS) time as determined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 from day of randomization until disease progression or death for patients randomised to combination therapy with afatinib plus paclitaxel or to investigator's choice of chemotherapy.

Median was calculated from the Kaplan−Meier curve.

Time Frame From randomization until disease progression or death; Up to 32 months
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set: This analysis set consist of all randomised patients irrespective of whether treated or not.
Arm/Group Title Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description:
Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Overall Number of Participants Analyzed 138 68
Median (95% Confidence Interval)
Unit of Measure: Months
5.55
(5.06 to 6.31)
2.89
(1.87 to 3.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib Plus Paclitaxel (Part B), Investigators Choice of Chemotherapy (Part B)
Comments Hazard ratio is calculated from Cox proportional hazard model with treatment as the only factor, stratified by gender and maximum duration of erlotinib or gefitinib (<6 months vs >=6 months).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0030
Comments P−value is calculated from two−sided stratified log−rank test
Method stratified log−rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.44 to 0.85
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (Part A)
Hide Description

Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A.

Median was calculated from the Kaplan−Meier curve.

Time Frame From first dose administration until disease progression or death; Up to 51 months
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib Monotherapy (Part A)
Hide Arm/Group Description:
Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
Overall Number of Participants Analyzed 1154
Median (95% Confidence Interval)
Unit of Measure: Months
3.15
(2.83 to 3.71)
3.Secondary Outcome
Title Overall Survival (Part B)
Hide Description

Overall survival (OS) as determined by the time from randomization to death in part B.

Median was calculated from the Kaplan−Meier curve.

Time Frame From randomization until death; Up to 32 months
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description:
Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Overall Number of Participants Analyzed 138 68
Median (95% Confidence Interval)
Unit of Measure: Months
12.25
(10.91 to 14.88)
13.08
(9.86 to 15.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib Plus Paclitaxel (Part B), Investigators Choice of Chemotherapy (Part B)
Comments Hazard ratio was calculated from Cox proportional hazard model with treatment as the only factor, stratified by gender and maximum duration of erlotinib or gefitinib (<6 months vs >=6 months).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7905
Comments [Not Specified]
Method Stratified log−rank test.
Comments P−value is calculated from two−sided stratified log−rank test.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.76 to 1.44
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Objective Response (Part A)
Hide Description Objective response defined as the best overall response of complete response [CR]: disappearance of all target lesion & partial response [PR]: ≥30% decrease in the sum of the longest diameter of target lesions , taking as reference the baseline sum longest diameter of Afatinib monotherapy according to RECIST 1.1 for Part A.
Time Frame Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib Monotherapy (Part A)
Hide Arm/Group Description:
Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
Overall Number of Participants Analyzed 1154
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
8.5
(6.9 to 10.3)
5.Secondary Outcome
Title Objective Response (Part B)
Hide Description Objective response (CR, PR) of Afatinib/paclitaxel combination therapy and comparator chemotherapy in Part B after progression in Part A according to RECIST 1.1 .
Time Frame Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Set
Arm/Group Title Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description:
Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Overall Number of Participants Analyzed 138 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
31.2
(23.6 to 39.6)
13.2
(6.2 to 23.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib Plus Paclitaxel (Part B), Investigators Choice of Chemotherapy (Part B)
Comments Odds ratio, 95% Confidence Interval (CI) and p−value (two−sided) from logistic regression stratified for maximum treatment duration of prior erlotinib or gefitinib (>=6 months vs <6 months) and gender.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.980
Confidence Interval (2-Sided) 95%
1.357 to 6.543
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Intensity and Incidence of Adverse Events (AEs) for Part A & Part B.
Hide Description Safety of Afatinib as indicated by intensity and incidence of adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0 both for Part A and Part B. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time Frame From first administration of treatment until 28 days after last drug administration, up to 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, up to 32 Months (Part B)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set
Arm/Group Title Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description:
Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Overall Number of Participants Analyzed 1154 134 60
Measure Type: Number
Unit of Measure: Percentage of participants
Grade 1 8.6 4.5 8.3
Grade 2 28.0 26.1 26.7
Grade 3 41.1 44.0 38.3
Grade 4 4.9 9.7 6.7
Grade 5 16.6 12.7 6.7
Time Frame From first administration of treatment until 28 days after last drug administration, upto 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, upto 32 Months (Part B).
Adverse Event Reporting Description Part A-events that started within the period defined by the first administration of afatinib until randomization into Part B or 28 days after the last administration of afatinib, whichever occurred first. Part B-events that started within the period from randomization through 28 days after the last administration of trial medication.
 
Arm/Group Title Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Hide Arm/Group Description Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme). Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics). Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
All-Cause Mortality
Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   471/1154 (40.81%)   54/134 (40.30%)   19/60 (31.67%) 
Blood and lymphatic system disorders       
Anaemia  1  4/1154 (0.35%)  1/134 (0.75%)  0/60 (0.00%) 
Febrile neutropenia  1  0/1154 (0.00%)  1/134 (0.75%)  1/60 (1.67%) 
Leukopenia  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Neutropenia  1  0/1154 (0.00%)  1/134 (0.75%)  1/60 (1.67%) 
Disseminated intravascular coagulation  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Thrombocytopenia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Cardiac disorders       
Arrhythmia  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Acute coronary syndrome  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Acute left ventricular failure  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Atrial fibrillation  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Atrioventricular block complete  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Bradycardia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Cardiac failure  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Cardiac tamponade  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Cardiopulmonary failure  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Coronary artery disease  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Left ventricular dysfunction  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Myocardial infarction  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Pericardial effusion  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Tachycardia  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Congenital, familial and genetic disorders       
Tracheo-oesophageal fistula  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Eye disorders       
Diplopia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Retinal detachment  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Vision blurred  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  6/1154 (0.52%)  2/134 (1.49%)  1/60 (1.67%) 
Ascites  1  4/1154 (0.35%)  1/134 (0.75%)  0/60 (0.00%) 
Diarrhoea  1  59/1154 (5.11%)  6/134 (4.48%)  0/60 (0.00%) 
Gastrointestinal disorder  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Gingival bleeding  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Haemorrhoids  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Nausea  1  8/1154 (0.69%)  1/134 (0.75%)  0/60 (0.00%) 
Pancreatitis  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Rectal haemorrhage  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Rectal prolapse  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Vomiting  1  18/1154 (1.56%)  1/134 (0.75%)  0/60 (0.00%) 
Abdominal pain upper  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Constipation  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Duodenal ulcer  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Dysphagia  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Epigastric discomfort  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Gastritis haemorrhagic  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Gastrointestinal hypomotility  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Gastrooesophageal reflux disease  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Haematemesis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Ileus  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Ileus paralytic  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Intestinal obstruction  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Jejunal perforation  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pancreatitis acute  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Peritoneal haemorrhage  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Small intestinal obstruction  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Stomatitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Vomiting projectile  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
General disorders       
Adverse drug reaction  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Asthenia  1  8/1154 (0.69%)  1/134 (0.75%)  0/60 (0.00%) 
Chest pain  1  8/1154 (0.69%)  1/134 (0.75%)  1/60 (1.67%) 
Extravasation  1  0/1154 (0.00%)  0/134 (0.00%)  1/60 (1.67%) 
General physical health deterioration  1  45/1154 (3.90%)  7/134 (5.22%)  1/60 (1.67%) 
Pyrexia  1  9/1154 (0.78%)  1/134 (0.75%)  1/60 (1.67%) 
Chest discomfort  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Death  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Fatigue  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Gravitational oedema  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hyperthermia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Local swelling  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Malaise  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Mucosal inflammation  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Multi-organ failure  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Oedema  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pain  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Performance status decreased  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Sudden death  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Cholangitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Cholestasis  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Hepatic failure  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hepatic mass  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hepatic pain  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hepatitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Liver injury  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Infections and infestations       
Bacterial infection  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Bronchitis  1  2/1154 (0.17%)  2/134 (1.49%)  0/60 (0.00%) 
Cellulitis  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Empyema  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Infectious pleural effusion  1  1/1154 (0.09%)  1/134 (0.75%)  0/60 (0.00%) 
Lower respiratory tract infection  1  5/1154 (0.43%)  2/134 (1.49%)  0/60 (0.00%) 
Nasopharyngitis  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Pneumonia  1  42/1154 (3.64%)  4/134 (2.99%)  3/60 (5.00%) 
Pneumonia bacterial  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Respiratory tract infection  1  5/1154 (0.43%)  3/134 (2.24%)  0/60 (0.00%) 
Urinary tract infection  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Aspergillus infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Catheter site infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Device related infection  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Endocarditis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Erysipelas  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Escherichia sepsis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Fungal infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Gastroenteritis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Herpes zoster  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Infection  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Kidney infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Laryngitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Lobar pneumonia  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Localised infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Lung abscess  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Lung infection  1  11/1154 (0.95%)  0/134 (0.00%)  0/60 (0.00%) 
Lymphangitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Meningitis bacterial  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Paronychia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Peritonitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Respiratory tract infection viral  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Sepsis  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Septic shock  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Skin bacterial infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Staphylococcal infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Staphylococcal skin infection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Upper respiratory tract infection  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Urosepsis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Injury, poisoning and procedural complications       
Fracture displacement  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Overdose  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Compression fracture  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Fall  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Femoral neck fracture  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Femur fracture  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Ligament sprain  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pelvic fracture  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Post procedural complication  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Road traffic accident  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Spinal compression fracture  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Investigations       
Biopsy lymph gland abnormal  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Gene mutation identification test  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Weight decreased  1  0/1154 (0.00%)  2/134 (1.49%)  0/60 (0.00%) 
Glomerular filtration rate decreased  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Haemoglobin decreased  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Oxygen saturation decreased  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Staphylococcus test positive  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  12/1154 (1.04%)  2/134 (1.49%)  0/60 (0.00%) 
Dehydration  1  15/1154 (1.30%)  1/134 (0.75%)  0/60 (0.00%) 
Fluid retention  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypokalaemia  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Hyponatraemia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypophosphataemia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypoproteinaemia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypovolaemia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  11/1154 (0.95%)  1/134 (0.75%)  0/60 (0.00%) 
Musculoskeletal chest pain  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Osteoporosis  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Spinal pain  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Arthralgia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Bone pain  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Intervertebral disc protrusion  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Mobility decreased  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Muscular weakness  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Musculoskeletal pain  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Neck pain  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Osteonecrosis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pain in extremity  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pathological fracture  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant neoplasm progression  1  46/1154 (3.99%)  2/134 (1.49%)  0/60 (0.00%) 
Metastases to central nervous system  1  7/1154 (0.61%)  3/134 (2.24%)  1/60 (1.67%) 
Metastases to meninges  1  2/1154 (0.17%)  2/134 (1.49%)  0/60 (0.00%) 
Metastasis  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Neoplasm progression  1  19/1154 (1.65%)  2/134 (1.49%)  2/60 (3.33%) 
Pericarditis malignant  1  1/1154 (0.09%)  1/134 (0.75%)  0/60 (0.00%) 
Brain neoplasm  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Lung neoplasm  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Malignant ascites  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Malignant neoplasm of pleura  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Malignant pleural effusion  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Metastases to bone  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Metastases to liver  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Metastases to peritoneum  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Metastases to pleura  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Metastases to spine  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Metastatic pain  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Non-small cell lung cancer  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Parathyroid tumour benign  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Tumour compression  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Tumour pain  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Nervous system disorders       
Cognitive disorder  1  1/1154 (0.09%)  1/134 (0.75%)  0/60 (0.00%) 
Headache  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Hydrocephalus  1  0/1154 (0.00%)  0/134 (0.00%)  1/60 (1.67%) 
Intracranial pressure increased  1  3/1154 (0.26%)  1/134 (0.75%)  0/60 (0.00%) 
Nervous system disorder  1  1/1154 (0.09%)  0/134 (0.00%)  1/60 (1.67%) 
Seizure  1  6/1154 (0.52%)  1/134 (0.75%)  1/60 (1.67%) 
Altered state of consciousness  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Ataxia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Brain oedema  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Cerebral haemorrhage  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Cerebrovascular accident  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Cervicobrachial syndrome  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Dizziness  1  5/1154 (0.43%)  0/134 (0.00%)  0/60 (0.00%) 
Dysarthria  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Epilepsy  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Monoplegia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Paraparesis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Reversible ischaemic neurological deficit  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Sciatica  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Somnolence  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Speech disorder  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Spinal cord compression  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Syncope  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Psychiatric disorders       
Completed suicide  1  1/1154 (0.09%)  0/134 (0.00%)  1/60 (1.67%) 
Confusional state  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Depression  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Mental status changes  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  9/1154 (0.78%)  1/134 (0.75%)  0/60 (0.00%) 
Renal failure  1  4/1154 (0.35%)  1/134 (0.75%)  0/60 (0.00%) 
Anuria  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Haematuria  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Renal colic  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Urinary retention  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  67/1154 (5.81%)  5/134 (3.73%)  3/60 (5.00%) 
Haemoptysis  1  7/1154 (0.61%)  1/134 (0.75%)  0/60 (0.00%) 
Hypercapnia  1  0/1154 (0.00%)  0/134 (0.00%)  1/60 (1.67%) 
Interstitial lung disease  1  6/1154 (0.52%)  1/134 (0.75%)  1/60 (1.67%) 
Lung disorder  1  1/1154 (0.09%)  2/134 (1.49%)  0/60 (0.00%) 
Pleural effusion  1  49/1154 (4.25%)  3/134 (2.24%)  1/60 (1.67%) 
Pneumothorax  1  6/1154 (0.52%)  2/134 (1.49%)  0/60 (0.00%) 
Pulmonary embolism  1  17/1154 (1.47%)  4/134 (2.99%)  1/60 (1.67%) 
Respiratory arrest  1  1/1154 (0.09%)  1/134 (0.75%)  0/60 (0.00%) 
Respiratory failure  1  13/1154 (1.13%)  1/134 (0.75%)  0/60 (0.00%) 
Acute pulmonary oedema  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Acute respiratory distress syndrome  1  8/1154 (0.69%)  0/134 (0.00%)  0/60 (0.00%) 
Acute respiratory failure  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Asphyxia  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Atelectasis  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Choking  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Chronic obstructive pulmonary disease  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Cough  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Haemothorax  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hydrothorax  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypoxia  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Obstructive airways disorder  1  3/1154 (0.26%)  0/134 (0.00%)  0/60 (0.00%) 
Pleural fibrosis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pneumonia aspiration  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pneumonitis  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Productive cough  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Pulmonary haemorrhage  1  4/1154 (0.35%)  0/134 (0.00%)  0/60 (0.00%) 
Pulmonary oedema  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Respiratory acidosis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Thoracic haemorrhage  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Skin and subcutaneous tissue disorders       
Petechiae  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Rash  1  1/1154 (0.09%)  1/134 (0.75%)  0/60 (0.00%) 
Rash erythematous  1  0/1154 (0.00%)  1/134 (0.75%)  0/60 (0.00%) 
Skin erosion  1  0/1154 (0.00%)  0/134 (0.00%)  1/60 (1.67%) 
Decubitus ulcer  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Dermatitis acneiform  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Skin toxicity  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Surgical and medical procedures       
Lung transplant  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Partial lung resection  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Vascular disorders       
Shock  1  2/1154 (0.17%)  1/134 (0.75%)  0/60 (0.00%) 
Deep vein thrombosis  1  6/1154 (0.52%)  0/134 (0.00%)  0/60 (0.00%) 
Embolism  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Haemorrhage  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Hypotension  1  2/1154 (0.17%)  0/134 (0.00%)  0/60 (0.00%) 
Neurogenic shock  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Phlebitis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Raynaud's phenomenon  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Superior vena cava syndrome  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Thrombosis  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Venous thrombosis limb  1  1/1154 (0.09%)  0/134 (0.00%)  0/60 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Afatinib Monotherapy (Part A) Afatinib Plus Paclitaxel (Part B) Investigators Choice of Chemotherapy (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1129/1154 (97.83%)   128/134 (95.52%)   50/60 (83.33%) 
Blood and lymphatic system disorders       
Anaemia  1  80/1154 (6.93%)  33/134 (24.63%)  6/60 (10.00%) 
Leukopenia  1  5/1154 (0.43%)  20/134 (14.93%)  7/60 (11.67%) 
Neutropenia  1  7/1154 (0.61%)  26/134 (19.40%)  8/60 (13.33%) 
Gastrointestinal disorders       
Abdominal pain  1  90/1154 (7.80%)  11/134 (8.21%)  4/60 (6.67%) 
Abdominal pain upper  1  65/1154 (5.63%)  19/134 (14.18%)  4/60 (6.67%) 
Constipation  1  85/1154 (7.37%)  22/134 (16.42%)  10/60 (16.67%) 
Diarrhoea  1  964/1154 (83.54%)  72/134 (53.73%)  4/60 (6.67%) 
Nausea  1  252/1154 (21.84%)  28/134 (20.90%)  14/60 (23.33%) 
Stomatitis  1  303/1154 (26.26%)  14/134 (10.45%)  2/60 (3.33%) 
Vomiting  1  211/1154 (18.28%)  31/134 (23.13%)  4/60 (6.67%) 
Mouth ulceration  1  91/1154 (7.89%)  2/134 (1.49%)  0/60 (0.00%) 
General disorders       
Asthenia  1  200/1154 (17.33%)  47/134 (35.07%)  18/60 (30.00%) 
Chest pain  1  82/1154 (7.11%)  9/134 (6.72%)  2/60 (3.33%) 
Fatigue  1  136/1154 (11.79%)  32/134 (23.88%)  10/60 (16.67%) 
Mucosal inflammation  1  200/1154 (17.33%)  13/134 (9.70%)  0/60 (0.00%) 
Oedema peripheral  1  57/1154 (4.94%)  12/134 (8.96%)  2/60 (3.33%) 
Pyrexia  1  82/1154 (7.11%)  18/134 (13.43%)  7/60 (11.67%) 
Infections and infestations       
Bronchitis  1  21/1154 (1.82%)  7/134 (5.22%)  2/60 (3.33%) 
Conjunctivitis  1  79/1154 (6.85%)  12/134 (8.96%)  0/60 (0.00%) 
Nasopharyngitis  1  35/1154 (3.03%)  10/134 (7.46%)  2/60 (3.33%) 
Paronychia  1  342/1154 (29.64%)  23/134 (17.16%)  0/60 (0.00%) 
Pneumonia  1  68/1154 (5.89%)  8/134 (5.97%)  1/60 (1.67%) 
Rhinitis  1  54/1154 (4.68%)  7/134 (5.22%)  4/60 (6.67%) 
Upper respiratory tract infection  1  32/1154 (2.77%)  7/134 (5.22%)  1/60 (1.67%) 
Urinary tract infection  1  62/1154 (5.37%)  14/134 (10.45%)  1/60 (1.67%) 
Folliculitis  1  86/1154 (7.45%)  5/134 (3.73%)  0/60 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  28/1154 (2.43%)  8/134 (5.97%)  2/60 (3.33%) 
Haemoglobin decreased  1  11/1154 (0.95%)  7/134 (5.22%)  0/60 (0.00%) 
Weight decreased  1  132/1154 (11.44%)  16/134 (11.94%)  3/60 (5.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  304/1154 (26.34%)  37/134 (27.61%)  10/60 (16.67%) 
Hypokalaemia  1  51/1154 (4.42%)  12/134 (8.96%)  3/60 (5.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  46/1154 (3.99%)  8/134 (5.97%)  2/60 (3.33%) 
Back pain  1  94/1154 (8.15%)  8/134 (5.97%)  5/60 (8.33%) 
Musculoskeletal pain  1  48/1154 (4.16%)  8/134 (5.97%)  0/60 (0.00%) 
Myalgia  1  17/1154 (1.47%)  10/134 (7.46%)  7/60 (11.67%) 
Pain in extremity  1  60/1154 (5.20%)  8/134 (5.97%)  5/60 (8.33%) 
Nervous system disorders       
Dizziness  1  60/1154 (5.20%)  13/134 (9.70%)  4/60 (6.67%) 
Dysgeusia  1  25/1154 (2.17%)  7/134 (5.22%)  4/60 (6.67%) 
Headache  1  56/1154 (4.85%)  16/134 (11.94%)  6/60 (10.00%) 
Hypoaesthesia  1  6/1154 (0.52%)  9/134 (6.72%)  5/60 (8.33%) 
Neuropathy peripheral  1  8/1154 (0.69%)  16/134 (11.94%)  7/60 (11.67%) 
Paraesthesia  1  25/1154 (2.17%)  13/134 (9.70%)  2/60 (3.33%) 
Peripheral sensory neuropathy  1  4/1154 (0.35%)  8/134 (5.97%)  2/60 (3.33%) 
Psychiatric disorders       
Insomnia  1  39/1154 (3.38%)  9/134 (6.72%)  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  194/1154 (16.81%)  32/134 (23.88%)  13/60 (21.67%) 
Dysphonia  1  36/1154 (3.12%)  7/134 (5.22%)  2/60 (3.33%) 
Dyspnoea  1  194/1154 (16.81%)  34/134 (25.37%)  11/60 (18.33%) 
Epistaxis  1  151/1154 (13.08%)  19/134 (14.18%)  3/60 (5.00%) 
Oropharyngeal pain  1  30/1154 (2.60%)  10/134 (7.46%)  1/60 (1.67%) 
Productive cough  1  47/1154 (4.07%)  6/134 (4.48%)  4/60 (6.67%) 
Rhinorrhoea  1  61/1154 (5.29%)  6/134 (4.48%)  4/60 (6.67%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  39/1154 (3.38%)  47/134 (35.07%)  10/60 (16.67%) 
Nail disorder  1  41/1154 (3.55%)  9/134 (6.72%)  2/60 (3.33%) 
Pruritus  1  179/1154 (15.51%)  13/134 (9.70%)  3/60 (5.00%) 
Rash  1  629/1154 (54.51%)  30/134 (22.39%)  7/60 (11.67%) 
Skin fissures  1  101/1154 (8.75%)  10/134 (7.46%)  1/60 (1.67%) 
Acne  1  87/1154 (7.54%)  5/134 (3.73%)  0/60 (0.00%) 
Dry skin  1  164/1154 (14.21%)  6/134 (4.48%)  0/60 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  71/1154 (6.15%)  2/134 (1.49%)  0/60 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01085136     History of Changes
Other Study ID Numbers: 1200.42
2009-014563-39 ( EudraCT Number: EudraCT )
First Submitted: March 10, 2010
First Posted: March 11, 2010
Results First Submitted: October 1, 2014
Results First Posted: October 3, 2014
Last Update Posted: April 4, 2017