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Trial of BIBW 2992 (Afatinib) + Cetuximab in Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01090011
Recruitment Status : Completed
First Posted : March 19, 2010
Results First Posted : July 21, 2014
Last Update Posted : October 2, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: Cetuximab
Drug: BIBW 2992
Enrollment 171
Recruitment Details  
Pre-assignment Details 171 patients were entered and treated in the study.
Arm/Group Title Total Patients
Hide Arm/Group Description All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events.
Period Title: Overall Study
Started 171
Completed 0
Not Completed 171
Reason Not Completed
Progressive disease             128
Adverse Event             32
Protocol Violation             1
Refusal to start/continue medication             5
Other reason not defined above             5
Arm/Group Title Total Patients
Hide Arm/Group Description All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events.
Overall Number of Baseline Participants 171
Hide Baseline Analysis Population Description
Treated set which includeed all patients enrolled in the trial who were documented to have taken at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 171 participants
58.1  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants
Female
119
  69.6%
Male
52
  30.4%
1.Primary Outcome
Title The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT).
Hide Description

A DLT was defined as an AE or laboratory abnormality that a) related to the study regimen; b) or met any of the following criteria:

  • CTCAE Grade 2 or higher decrease in cardiac left ventricular function
  • CTCAE Grade 2 diarrhea lasting for 7 or more days, despite appropriate use of standard anti-diarrheal therapy
  • CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for at least 2 days
  • CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days
  • CTCAE Grade ≥3 rash despite standard medical management
  • CTCAE Grade ≥3 fatigue lasting for more than 7 days
  • CTCAE Grade 4 hypomagnesaemia or Grade 3 hypomagnesaemia with clinical significant sequelae
  • All other toxicities of CTCAE Grade ≥3 (except alopecia, and allergic reaction) leading to an interruption of afatinib and/or cetuximab for more than 14 days until recovery to baseline or Grade 1, whichever was higher.
Time Frame from day 1 treatment until progression or undue toxicity, up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set for Cohort One. Cohort one was based on the data from the first treatment cycle where four patients received 'Afatinib 40+Cetuximab 250' and six patients received 'Afatinib 40+Cetuximab 500'.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with Acquired Resistance (AR) to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 6
Measure Type: Number
Unit of Measure: participants
0 0
2.Secondary Outcome
Title Highest CTCAE Grade
Hide Description Safety of afatinib when administered together with cetuximab as indicated by intensity and incidence of adverse events, graded according to the U.S. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version (v) 3.0
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the Maximum Tolerated Dose (MTD) determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
Patients with highest CTCAE Grade 1 0 0.8 10.8 2.8
Patients with highest CTCAE Grade 2 25.0 26.2 24.3 19.4
Patients with highest CTCAE Grade 3 50.0 54.0 48.6 52.8
Patients with highest CTCAE Grade 4 25.0 4.0 5.4 8.3
Patients with highest CTCAE Grade 5 0 15.1 10.8 16.7
3.Secondary Outcome
Title Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters
Hide Description [Not Specified]
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
Haemoglobin - low (N=4,124,35,35) 0 12.9 20.0 2.9
White blood cell ct. - low (N=4,124,35,35) 0 3.2 0 2.9
Neutrophils - low (N=4,124,35,35) 0 4.0 0 2.9
Sodium - low (N=4,124,35,35) 0 5.6 0 2.9
Potassium - low (N=4,124,35,35) 0 5.6 2.9 5.7
Potassium - high (N=4,124,35,35) 0 4.0 0 0
Calcium - low (N=4,124,35,35) 0 6.5 8.6 5.7
Calcium - high (N=4,124,35,35) 0 1.6 0 0
Magnesium - low (N=4,124,34,35) 0 9.7 0 11.4
AST/GOT, SGOT - high (N=4,123,35,35) 0 3.3 0 2.9
ALT/GPT, SGPT - high (N=4,123,35,35) 0 11.4 0 8.6
Alkaline phosphatase - high (N=4,124,35,35) 25.0 4.8 2.9 5.7
Blood urea nitrogen - high (N=missing,105,28,28) 0 5.7 3.6 0
Creatinine - high (N=4,123,33,35) 0 2.4 0 0
Creatinine clearance - low (N=4,123,33,35) 0 3.3 0 2.9
Bilirubin,total - high (N=4,124,35,35) 0 4.8 2.9 5.7
Sodium - high (N=4,124,35,35) 0 0.8 0 0
4.Secondary Outcome
Title Frequency (%) of Patients With Adverse Events Leading to Dose Reduction
Hide Description [Not Specified]
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
25.0 37.3 13.5 22.2
5.Secondary Outcome
Title Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation
Hide Description Frequency (%) of patients with adverse events leading to treatment discontinuation
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
50.0 23.8 2.7 19.4
6.Secondary Outcome
Title Frequency (%) of Patients With Adverse Events Leading to Death
Hide Description [Not Specified]
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
0.0 15.1 10.8 16.7
7.Secondary Outcome
Title Frequency (%) of Patients With Related Serious Adverse Events
Hide Description Frequency (%) of patients with drug-related serious adverse events
Time Frame From first drug administration to 28 days after discontinuation of drug intake up to 915 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
0.0 10.3 5.4 2.8
8.Secondary Outcome
Title Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm
Hide Description Area Under the Concentration-time Curve (AUC) of Afatinib in plasma at steady state over a uniform dosing interval tau (15 days) (AUCtau,ss) after oral administration of Afatinib and cetuximab combination therapy
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
1300
(21.8%)
935
(59.8%)
9.Secondary Outcome
Title Concentration of Afatinib in Plasma for the Combination Arm
Hide Description Minimum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmin,ss). Maximum measured concentration of Afatinib in plasma at steady state over 15 day dosing interval (Cmax,ss).
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmin,ss,15
33.9
(19.6%)
24.4
(53.7%)
Cmax,ss,15
83.8
(19.8%)
52.3
(73.2%)
10.Secondary Outcome
Title Peak-trough Fluctuation (PTF)
Hide Description Peak-trough fluctuation (PTF) of plasma afatinib for the combination arm. PTF = 100*(Cmax-Cmin)/Caverage where Caverage = AUC/time, where time equals 24 hours.
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: % of average concentration
91.6
(15.9%)
73.8
(55.2%)
11.Secondary Outcome
Title t1/2,ss
Hide Description Terminal half-life of Afatinib in plasma at steady state (t1/2,ss)
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
22.4
(24.5%)
NA [1] 
(NA%)
[1]
No descriptive statistics calculated due to insufficient number of participants with data
12.Secondary Outcome
Title MRTpo,ss
Hide Description mean residence time of Afatinib in the body at steady state after oral administration (MRTpo,ss) for 15 days
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
32.6
(23.4%)
NA [1] 
(NA%)
[1]
no descriptive statistics calculated due to insufficient number of participants with data
13.Secondary Outcome
Title CL/F,ss,15
Hide Description Apparent clearance of afatinib in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/min
511
(21.8%)
713
(59.8%)
14.Secondary Outcome
Title Vz/F,ss
Hide Description Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss) for 15 days
Time Frame Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 3 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
991
(44.8%)
NA [1] 
(NA%)
[1]
no descriptive statistics calculated due to insufficient number of participants with data
15.Secondary Outcome
Title Predose Plasma Concentrations of Afatinib for the Combination Arm
Hide Description Predose plasma concentrations (Cpre,ss) of Afatinib at Course 1, Visit 2, 3, 4 and 5, at Course 2, Visit 1 and 2 and at Course 3, Visit 1.
Time Frame Up to 57 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic dataset (PKS)
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cpre,ss,8 (N=4,25)
33.2
(38.3%)
28.3
(62.3%)
Cpre,ss,15 (N=3,28)
33.9
(19.6%)
27.1
(51.3%)
Cpre,ss,16 (N=3,0)
36.4
(15.8%)
NA [1] 
(NA%)
Cpre,ss,22 (N=3,21)
33.5
(1.30%)
28.3
(64.3%)
Cpre,ss,29 (N=3,20)
33.4
(21.8%)
27.7
(56.8%)
Cpre,ss,43 (N=3,19)
33.5
(14.9%)
26.0
(98.4%)
Cpre,ss,57 (N=3,0)
36.6
(4.51%)
NA [1] 
(NA%)
[1]
no descriptive statistics calculated due to insufficient number of participants with data
16.Secondary Outcome
Title Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1)
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Disease control = CR + PR + SD.
Time Frame up to 116 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
75.0
(19.4 to 99.4)
70.6
(61.9 to 78.4)
56.8
(39.5 to 72.9)
50.0
(32.9 to 67.1)
17.Secondary Outcome
Title Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1)
Hide Description

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesion(s); Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Objective tumor response = CR + PR.

Time Frame up to 116 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Measure Type: Number
Unit of Measure: percentage of patients
0.0 28.6 5.4 11.1
18.Secondary Outcome
Title Duration of Objective Response (According to RECIST v1.1)
Hide Description Duration of objective response was measured from the time measurements criteria were met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since treatment started).
Time Frame up to 116 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Mean (Standard Deviation)
Unit of Measure: months
0  (0) 9.00  (6.94) 3.90  (0.07) 5.80  (2.36)
19.Secondary Outcome
Title Duration of Disease Control (According to RECIST v1.1)
Hide Description Duration of disease control was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence SD, PR or CR.
Time Frame up to 116 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Mean (Standard Deviation)
Unit of Measure: months
7.40  (5.54) 7.40  (5.45) 4.90  (3.08) 5.90  (4.51)
20.Secondary Outcome
Title Progression-Free Survival (PFS) Time
Hide Description Progression-Free Survival was defined as the duration of time from start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to RECIST 1.1) or death.
Time Frame up to 116 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set. 32 patients in the Afa40-mono group had disease progression and were transitioned to treatment with Afa40+Ctx500. Thus the total of 203 patients (4+126+37+36) minus the 32 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description:

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250)

Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg (Afa40 Mono)

Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib)

Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)

Overall Number of Participants Analyzed 4 126 37 36
Median (95% Confidence Interval)
Unit of Measure: months
4.2
(1.4 to 13.8)
4.6
(4.2 to 6.3)
2.7
(1.1 to 3.7)
2.9
(1.8 to 4.8)
Time Frame Up to 915 days
Adverse Event Reporting Description 32 patients in the 'Afa40-mono' group had disease progression and were transitioned to treatment with 'Afa40+Ctx500'. Thus the total of 203 patients (4+126+37+36) minus the 321 patients counted in both 'Afa-mono' and 'Afa40+Ctx500' treatments arms equals 171, the total number of patients started in participant flow section.
 
Arm/Group Title Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Hide Arm/Group Description Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 250 mg/m2 (Afa40+Ctx250) Combination Arm (includes the initial dose escalation and expansion cohort of upfront afatinib plus cetuximab in patients with AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500) Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib) Afatinib 40 mg (Afa40 Mono) Sequential Arm (includes patients who received afatinib monotherapy and upon progression the combination of afatinib and cetuximab at the MTD determined in the combination arm. Patients still needed to have met the criteria for AR to erlotinib or gefitinib) Afatinib 40 mg + cetuximab 500 mg/m2 (Afa40+Ctx500)
All-Cause Mortality
Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/4 (75.00%)   63/126 (50.00%)   12/37 (32.43%)   15/36 (41.67%) 
Blood and lymphatic system disorders         
Leukocytosis  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Cardiac disorders         
Atrial fibrillation  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Endocrine disorders         
Steroid withdrawal syndrome  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Eye disorders         
Diplopia  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders         
Abdominal discomfort  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Abdominal distension  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Abdominal pain  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Ascites  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Diarrhoea  1  0/4 (0.00%)  4/126 (3.17%)  1/37 (2.70%)  0/36 (0.00%) 
Dysphagia  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Gastritis  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Gastrointestinal haemorrhage  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Gastrooesophageal reflux disease  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Nausea  1  0/4 (0.00%)  4/126 (3.17%)  2/37 (5.41%)  1/36 (2.78%) 
Vomiting  1  0/4 (0.00%)  6/126 (4.76%)  3/37 (8.11%)  1/36 (2.78%) 
General disorders         
Catheter site pain  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Chest pain  1  1/4 (25.00%)  1/126 (0.79%)  1/37 (2.70%)  0/36 (0.00%) 
Chills  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Death  1  0/4 (0.00%)  2/126 (1.59%)  1/37 (2.70%)  0/36 (0.00%) 
Fatigue  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  0/36 (0.00%) 
General physical health deterioration  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Mucosal inflammation  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Oedema peripheral  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Pain  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Pyrexia  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  2/36 (5.56%) 
Sudden death  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hepatobiliary disorders         
Hepatic failure  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hepatic function abnormal  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hyperbilirubinaemia  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Immune system disorders         
Drug hypersensitivity  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  0/36 (0.00%) 
Hypersensitivity  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Infections and infestations         
Cellulitis  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Cystitis  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Gastroenteritis  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Gastroenteritis viral  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Infectious pleural effusion  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Meningitis aseptic  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Pneumonia  1  0/4 (0.00%)  3/126 (2.38%)  1/37 (2.70%)  3/36 (8.33%) 
Sepsis  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Streptococcal infection  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Urinary tract infection  1  0/4 (0.00%)  2/126 (1.59%)  1/37 (2.70%)  1/36 (2.78%) 
Viral infection  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Injury, poisoning and procedural complications         
Fall  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Femur fracture  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hip fracture  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Spinal compression fracture  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Spinal fracture  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Investigations         
Biopsy lung  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Dehydration  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  0/36 (0.00%) 
Failure to thrive  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hypercalcaemia  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Hypokalaemia  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hyponatraemia  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Back pain  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Bone pain  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Musculoskeletal chest pain  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Musculoskeletal pain  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Pain in extremity  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Spinal pain  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Bladder cancer  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Malignant neoplasm progression  1  2/4 (50.00%)  6/126 (4.76%)  2/37 (5.41%)  4/36 (11.11%) 
Metastasis  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Neoplasm progression  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Nervous system disorders         
Cerebrovascular accident  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Convulsion  1  0/4 (0.00%)  4/126 (3.17%)  0/37 (0.00%)  0/36 (0.00%) 
Depressed level of consciousness  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Dizziness  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Drug withdrawal headache  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Embolic cerebral infarction  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Generalised tonic-clonic seizure  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Headache  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Spinal cord compression  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Syncope  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  1/36 (2.78%) 
Psychiatric disorders         
Confusional state  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hallucination  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Mental status changes  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Cough  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Dyspnoea  1  0/4 (0.00%)  14/126 (11.11%)  2/37 (5.41%)  2/36 (5.56%) 
Haemoptysis  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hypoxia  1  0/4 (0.00%)  4/126 (3.17%)  1/37 (2.70%)  0/36 (0.00%) 
Lung infiltration  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Pleural effusion  1  0/4 (0.00%)  6/126 (4.76%)  1/37 (2.70%)  0/36 (0.00%) 
Pneumonitis  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Pneumothorax  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Pulmonary embolism  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  1/36 (2.78%) 
Pulmonary mass  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Respiratory failure  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  1/36 (2.78%) 
Surgical and medical procedures         
Pain management  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Surgery  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Vascular disorders         
Deep vein thrombosis  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  1/36 (2.78%) 
Embolism  1  0/4 (0.00%)  0/126 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Hypotension  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Arm - Afa40+Ctx250 Combination Arm - Afa40+Ctx500 Sequential Arm - Afatanib Monotherapy (Afa40 Mono) Sequential Arm - Combination Therapy (Afa40+Ctx500)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   126/126 (100.00%)   36/37 (97.30%)   36/36 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  3/36 (8.33%) 
Ear and labyrinth disorders         
Ear pain  1  1/4 (25.00%)  2/126 (1.59%)  0/37 (0.00%)  1/36 (2.78%) 
Ear pruritus  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Eye disorders         
Dry eye  1  0/4 (0.00%)  13/126 (10.32%)  2/37 (5.41%)  3/36 (8.33%) 
Eye irritation  1  0/4 (0.00%)  9/126 (7.14%)  1/37 (2.70%)  1/36 (2.78%) 
Lacrimation increased  1  0/4 (0.00%)  9/126 (7.14%)  0/37 (0.00%)  0/36 (0.00%) 
Vision blurred  1  0/4 (0.00%)  8/126 (6.35%)  2/37 (5.41%)  5/36 (13.89%) 
Gastrointestinal disorders         
Abdominal pain  1  0/4 (0.00%)  10/126 (7.94%)  0/37 (0.00%)  2/36 (5.56%) 
Abdominal pain upper  1  1/4 (25.00%)  4/126 (3.17%)  0/37 (0.00%)  1/36 (2.78%) 
Aphthous stomatitis  1  1/4 (25.00%)  2/126 (1.59%)  2/37 (5.41%)  0/36 (0.00%) 
Cheilitis  1  0/4 (0.00%)  13/126 (10.32%)  3/37 (8.11%)  0/36 (0.00%) 
Constipation  1  1/4 (25.00%)  32/126 (25.40%)  3/37 (8.11%)  6/36 (16.67%) 
Diarrhoea  1  2/4 (50.00%)  92/126 (73.02%)  27/37 (72.97%)  13/36 (36.11%) 
Dry mouth  1  1/4 (25.00%)  14/126 (11.11%)  0/37 (0.00%)  4/36 (11.11%) 
Glossodynia  1  1/4 (25.00%)  5/126 (3.97%)  1/37 (2.70%)  2/36 (5.56%) 
Haemorrhoids  1  0/4 (0.00%)  4/126 (3.17%)  1/37 (2.70%)  2/36 (5.56%) 
Large intestinal haemorrhage  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Lip dry  1  0/4 (0.00%)  1/126 (0.79%)  2/37 (5.41%)  1/36 (2.78%) 
Nausea  1  3/4 (75.00%)  64/126 (50.79%)  11/37 (29.73%)  12/36 (33.33%) 
Oral pain  1  0/4 (0.00%)  8/126 (6.35%)  0/37 (0.00%)  1/36 (2.78%) 
Stomatitis  1  1/4 (25.00%)  16/126 (12.70%)  4/37 (10.81%)  3/36 (8.33%) 
Tongue ulceration  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  2/36 (5.56%) 
Vomiting  1  1/4 (25.00%)  51/126 (40.48%)  7/37 (18.92%)  6/36 (16.67%) 
General disorders         
Asthenia  1  0/4 (0.00%)  7/126 (5.56%)  1/37 (2.70%)  3/36 (8.33%) 
Chest discomfort  1  0/4 (0.00%)  4/126 (3.17%)  0/37 (0.00%)  2/36 (5.56%) 
Chest pain  1  2/4 (50.00%)  6/126 (4.76%)  1/37 (2.70%)  2/36 (5.56%) 
Chills  1  0/4 (0.00%)  14/126 (11.11%)  2/37 (5.41%)  3/36 (8.33%) 
Face oedema  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Fatigue  1  3/4 (75.00%)  69/126 (54.76%)  16/37 (43.24%)  14/36 (38.89%) 
Feeling cold  1  0/4 (0.00%)  7/126 (5.56%)  1/37 (2.70%)  2/36 (5.56%) 
Mucosal inflammation  1  0/4 (0.00%)  32/126 (25.40%)  4/37 (10.81%)  2/36 (5.56%) 
Oedema peripheral  1  0/4 (0.00%)  12/126 (9.52%)  3/37 (8.11%)  4/36 (11.11%) 
Pain  1  1/4 (25.00%)  14/126 (11.11%)  1/37 (2.70%)  4/36 (11.11%) 
Pyrexia  1  0/4 (0.00%)  21/126 (16.67%)  8/37 (21.62%)  6/36 (16.67%) 
Xerosis  1  0/4 (0.00%)  53/126 (42.06%)  0/37 (0.00%)  0/36 (0.00%) 
Immune system disorders         
Drug hypersensitivity  1  0/4 (0.00%)  9/126 (7.14%)  0/37 (0.00%)  1/36 (2.78%) 
Infections and infestations         
Bronchitis  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  2/36 (5.56%) 
Candida infection  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  2/36 (5.56%) 
Eye infection  1  0/4 (0.00%)  4/126 (3.17%)  0/37 (0.00%)  2/36 (5.56%) 
Eyelid infection  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  2/36 (5.56%) 
Fungal infection  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  2/36 (5.56%) 
Impetigo  1  0/4 (0.00%)  12/126 (9.52%)  0/37 (0.00%)  0/36 (0.00%) 
Localised infection  1  0/4 (0.00%)  5/126 (3.97%)  0/37 (0.00%)  2/36 (5.56%) 
Nail infection  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  5/36 (13.89%) 
Nasopharyngitis  1  0/4 (0.00%)  9/126 (7.14%)  1/37 (2.70%)  1/36 (2.78%) 
Paronychia  1  2/4 (50.00%)  62/126 (49.21%)  6/37 (16.22%)  12/36 (33.33%) 
Pneumonia  1  0/4 (0.00%)  0/126 (0.00%)  2/37 (5.41%)  0/36 (0.00%) 
Rhinitis  1  0/4 (0.00%)  6/126 (4.76%)  2/37 (5.41%)  1/36 (2.78%) 
Skin infection  1  0/4 (0.00%)  6/126 (4.76%)  0/37 (0.00%)  3/36 (8.33%) 
Upper respiratory tract infection  1  0/4 (0.00%)  6/126 (4.76%)  3/37 (8.11%)  3/36 (8.33%) 
Urinary tract infection  1  0/4 (0.00%)  11/126 (8.73%)  5/37 (13.51%)  6/36 (16.67%) 
Investigations         
Haemoglobin decreased  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  2/36 (5.56%) 
Weight decreased  1  1/4 (25.00%)  10/126 (7.94%)  5/37 (13.51%)  4/36 (11.11%) 
Metabolism and nutrition disorders         
Appetite disorder  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Decreased appetite  1  2/4 (50.00%)  28/126 (22.22%)  7/37 (18.92%)  8/36 (22.22%) 
Dehydration  1  0/4 (0.00%)  2/126 (1.59%)  2/37 (5.41%)  5/36 (13.89%) 
Hypercalcaemia  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  1/36 (2.78%) 
Hyperglycaemia  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  2/36 (5.56%) 
Hypocalcaemia  1  0/4 (0.00%)  9/126 (7.14%)  0/37 (0.00%)  0/36 (0.00%) 
Hypokalaemia  1  0/4 (0.00%)  23/126 (18.25%)  3/37 (8.11%)  2/36 (5.56%) 
Hypomagnesaemia  1  1/4 (25.00%)  37/126 (29.37%)  3/37 (8.11%)  11/36 (30.56%) 
Hyponatraemia  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  3/36 (8.33%) 
Hypophosphataemia  1  0/4 (0.00%)  0/126 (0.00%)  0/37 (0.00%)  2/36 (5.56%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/4 (0.00%)  17/126 (13.49%)  1/37 (2.70%)  5/36 (13.89%) 
Back pain  1  1/4 (25.00%)  27/126 (21.43%)  9/37 (24.32%)  10/36 (27.78%) 
Flank pain  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  2/36 (5.56%) 
Muscle spasms  1  1/4 (25.00%)  14/126 (11.11%)  3/37 (8.11%)  4/36 (11.11%) 
Musculoskeletal pain  1  1/4 (25.00%)  11/126 (8.73%)  2/37 (5.41%)  2/36 (5.56%) 
Myalgia  1  0/4 (0.00%)  12/126 (9.52%)  1/37 (2.70%)  1/36 (2.78%) 
Pain in extremity  1  1/4 (25.00%)  12/126 (9.52%)  1/37 (2.70%)  3/36 (8.33%) 
Pain in jaw  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Nervous system disorders         
Cognitive disorder  1  0/4 (0.00%)  1/126 (0.79%)  2/37 (5.41%)  1/36 (2.78%) 
Dizziness  1  0/4 (0.00%)  17/126 (13.49%)  6/37 (16.22%)  6/36 (16.67%) 
Dysgeusia  1  0/4 (0.00%)  10/126 (7.94%)  0/37 (0.00%)  2/36 (5.56%) 
Headache  1  1/4 (25.00%)  53/126 (42.06%)  10/37 (27.03%)  10/36 (27.78%) 
Memory impairment  1  0/4 (0.00%)  1/126 (0.79%)  2/37 (5.41%)  1/36 (2.78%) 
Neuropathy peripheral  1  0/4 (0.00%)  11/126 (8.73%)  0/37 (0.00%)  0/36 (0.00%) 
Peripheral motor neuropathy  1  1/4 (25.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Peripheral sensory neuropathy  1  1/4 (25.00%)  7/126 (5.56%)  1/37 (2.70%)  0/36 (0.00%) 
Psychiatric disorders         
Anxiety  1  0/4 (0.00%)  2/126 (1.59%)  0/37 (0.00%)  2/36 (5.56%) 
Depression  1  0/4 (0.00%)  5/126 (3.97%)  2/37 (5.41%)  1/36 (2.78%) 
Insomnia  1  0/4 (0.00%)  11/126 (8.73%)  5/37 (13.51%)  5/36 (13.89%) 
Renal and urinary disorders         
Dysuria  1  1/4 (25.00%)  9/126 (7.14%)  0/37 (0.00%)  0/36 (0.00%) 
Haemoglobinuria  1  0/4 (0.00%)  1/126 (0.79%)  0/37 (0.00%)  2/36 (5.56%) 
Reproductive system and breast disorders         
Pelvic pain  1  0/4 (0.00%)  0/126 (0.00%)  2/37 (5.41%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/4 (50.00%)  41/126 (32.54%)  10/37 (27.03%)  11/36 (30.56%) 
Dysphonia  1  0/4 (0.00%)  10/126 (7.94%)  3/37 (8.11%)  2/36 (5.56%) 
Dyspnoea  1  1/4 (25.00%)  33/126 (26.19%)  7/37 (18.92%)  7/36 (19.44%) 
Epistaxis  1  2/4 (50.00%)  25/126 (19.84%)  5/37 (13.51%)  2/36 (5.56%) 
Hiccups  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Hypoxia  1  0/4 (0.00%)  2/126 (1.59%)  2/37 (5.41%)  1/36 (2.78%) 
Nasal congestion  1  0/4 (0.00%)  2/126 (1.59%)  2/37 (5.41%)  0/36 (0.00%) 
Nasal dryness  1  0/4 (0.00%)  3/126 (2.38%)  3/37 (8.11%)  0/36 (0.00%) 
Oropharyngeal pain  1  1/4 (25.00%)  13/126 (10.32%)  2/37 (5.41%)  1/36 (2.78%) 
Pleural effusion  1  0/4 (0.00%)  2/126 (1.59%)  2/37 (5.41%)  1/36 (2.78%) 
Pulmonary embolism  1  0/4 (0.00%)  2/126 (1.59%)  3/37 (8.11%)  1/36 (2.78%) 
Rhinorrhoea  1  0/4 (0.00%)  15/126 (11.90%)  4/37 (10.81%)  4/36 (11.11%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  1/4 (25.00%)  16/126 (12.70%)  2/37 (5.41%)  5/36 (13.89%) 
Dermatitis acneiform  1  1/4 (25.00%)  22/126 (17.46%)  7/37 (18.92%)  9/36 (25.00%) 
Dry skin  1  2/4 (50.00%)  39/126 (30.95%)  5/37 (13.51%)  13/36 (36.11%) 
Erythema  1  0/4 (0.00%)  14/126 (11.11%)  0/37 (0.00%)  1/36 (2.78%) 
Exfoliative rash  1  1/4 (25.00%)  3/126 (2.38%)  1/37 (2.70%)  2/36 (5.56%) 
Hair growth abnormal  1  0/4 (0.00%)  3/126 (2.38%)  0/37 (0.00%)  3/36 (8.33%) 
Hirsutism  1  0/4 (0.00%)  17/126 (13.49%)  0/37 (0.00%)  0/36 (0.00%) 
Hyperhidrosis  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  1/36 (2.78%) 
Pain of skin  1  0/4 (0.00%)  10/126 (7.94%)  0/37 (0.00%)  0/36 (0.00%) 
Photosensitivity reaction  1  0/4 (0.00%)  8/126 (6.35%)  0/37 (0.00%)  0/36 (0.00%) 
Pruritus  1  1/4 (25.00%)  50/126 (39.68%)  1/37 (2.70%)  6/36 (16.67%) 
Rash  1  1/4 (25.00%)  106/126 (84.13%)  14/37 (37.84%)  17/36 (47.22%) 
Rash erythematous  1  2/4 (50.00%)  2/126 (1.59%)  0/37 (0.00%)  0/36 (0.00%) 
Rash macular  1  2/4 (50.00%)  1/126 (0.79%)  0/37 (0.00%)  0/36 (0.00%) 
Skin fissures  1  1/4 (25.00%)  78/126 (61.90%)  5/37 (13.51%)  16/36 (44.44%) 
Skin hypertrophy  1  0/4 (0.00%)  2/126 (1.59%)  2/37 (5.41%)  0/36 (0.00%) 
Skin irritation  1  0/4 (0.00%)  7/126 (5.56%)  0/37 (0.00%)  1/36 (2.78%) 
Skin reaction  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Vascular disorders         
Haematoma  1  1/4 (25.00%)  1/126 (0.79%)  0/37 (0.00%)  1/36 (2.78%) 
Haemorrhage  1  0/4 (0.00%)  7/126 (5.56%)  0/37 (0.00%)  0/36 (0.00%) 
Hot flush  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Intra-abdominal haematoma  1  1/4 (25.00%)  0/126 (0.00%)  0/37 (0.00%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01090011    
Other Study ID Numbers: 1200.71
2009-015911-42 ( EudraCT Number: EudraCT )
First Submitted: March 10, 2010
First Posted: March 19, 2010
Results First Submitted: January 9, 2014
Results First Posted: July 21, 2014
Last Update Posted: October 2, 2015