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ADAM-Afatinib Diarrhea Assessment and Management

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ClinicalTrials.gov Identifier: NCT01814553
Recruitment Status : Completed
First Posted : March 20, 2013
Results First Posted : October 31, 2016
Last Update Posted : October 31, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: afatinib
Drug: loperamide
Enrollment 40
Recruitment Details  
Pre-assignment Details PD: Progressive Disease (PD)
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Period Title: Overall Study
Started 18 22
Completed 0 0
Not Completed 18 22
Reason Not Completed
PD per clinical progression             6             8
Other Adverse Event             4             5
Withdrawal by Subject             1             1
Other than stated             7             8
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2) Total
Hide Arm/Group Description Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2. Total of all reporting groups
Overall Number of Baseline Participants 18 22 40
Hide Baseline Analysis Population Description
Treated Set : This analysis set includes all entered patients who received at least one dose of investigational treatment (afatinib) and for whom there was documentation that they took at least 1 dose.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 22 participants 40 participants
69.70  (10.80) 68.00  (6.50) 68.80  (8.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 22 participants 40 participants
Female
12
  66.7%
12
  54.5%
24
  60.0%
Male
6
  33.3%
10
  45.5%
16
  40.0%
1.Primary Outcome
Title Occurence of CTCAE Grade >= 2 Diarrhea
Hide Description Overall incidence of patients who experienced diarrhea during the first three courses of afatinib treatment.
Time Frame From first drug administration until 28 days after the end of third treatment course, up to 84 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description:
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Overall Number of Participants Analyzed 18 22
Measure Type: Number
Unit of Measure: Percentage of participants
72.20 31.80
2.Secondary Outcome
Title Time to Initial Onset of Diarrhea Grade 2 or Higher
Hide Description Time to initial onset of diarrhea grade 2 or higher
Time Frame From first drug administration until end of third treatment course, up to 84 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description:
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Overall Number of Participants Analyzed 13 7
Mean (Standard Deviation)
Unit of Measure: days
23.50  (22.64) 15.40  (14.97)
3.Secondary Outcome
Title Duration of First Episode of Diarrhea Grade 2 or Higher
Hide Description

Duration of first episode of diarrhea grade 2 or higher.

Please note that the nine patients experienced diarrhea episodes that were not managed according to the protocol specified afatinib treatment interruptions and dose reductions. No patients were excluded from the primary analysis.

Time Frame From first drug administration until end of third treatment course, up to 84 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description:
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Overall Number of Participants Analyzed 13 7
Mean (Standard Deviation)
Unit of Measure: days
3.10  (4.09) 7.60  (5.19)
4.Secondary Outcome
Title Changes in Intensity of Diarrhea Over Time
Hide Description Percentage of participants with grade 2 or higher diarrhea each week for the first 3 cycles of afatinib treatment
Time Frame Up to 12 weeks (equivalent to 3 courses)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description:
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Overall Number of Participants Analyzed 18 22
Measure Type: Number
Unit of Measure: Percentage of participants
Grade 2: Week 1 (N=2, 1) 11.10 4.50
Grade 2: Week 2 (N=4, 3) 22.20 13.60
Grade 2: Week 3 (N=3, 3) 16.70 13.60
Grade 2: Week 4 (N=6, 2) 33.30 9.10
Grade 2: Week 5 (N=2, 0) 11.10 0.00
Grade 2: Week 6 (N=0, 1) 0.00 4.80
Grade 2: Week 7 (N=2, 1) 11.80 5.00
Grade 2: Week 8 (N=3, 0) 17.60 0.00
Grade 2: Week 9 (N=2, 0) 11.80 0.00
Grade 2: Week 10 (N=0, 0) 0.00 0.00
Grade 2: Week 11 (N=2, 0) 11.80 0.00
Grade 2: Week 12 (N=1, 1) 5.90 6.30
Grade >=3: Week 1 (N=1, 1) 5.60 4.50
Grade >=3: Week 2 (N=2, 2) 11.10 9.10
Grade >=3: Week 3 (N=3, 1) 16.70 4.50
Grade >=3: Week 4 (N=0, 1) 0.00 4.50
Grade >=3: Week 5 (N=0, 0) 0.00 0.00
Grade >=3: Week 6 (N=0, 0) 0.00 0.00
Grade >=3: Week 7 (N=1, 0) 5.90 0.00
Grade >=3: Week 8 (N=0, 0) 0.00 0.00
Grade >=3: Week 9 (N=0, 0) 0.00 0.00
Grade >=3: Week 10 (N=1, 0) 5.90 0.00
Grade >=3: Week 11 (N=0, 0) 0.00 0.00
Grade >=3: Week 12 (N=0, 0) 0.00 0.00
5.Secondary Outcome
Title PFS
Hide Description

Progression-free survival (PFS). PFS was defined as the time from the start of treatment to an event occurred. In the analyses for the PFS endpoint, an event was defined as disease progression or death, whichever occurred earlier. Data for patients who did not die or progress during the trial were censored at the time of afatinib discontinuation or transition to commercially available afatinib. Median PFS is estimated using Kaplan-Meier method.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1).

Time Frame Every 08 weeks during the first 6 months of treatment, and every 12 weeks thereafter until the end of treatment.
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Hide Analysis Population Description
Treated Set
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description:
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours.
Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
Overall Number of Participants Analyzed 18 22
Median (95% Confidence Interval)
Unit of Measure: Months
15.40 [1] 
(5.50 to NA)
9.90 [1] 
(5.50 to NA)
[1]
The upper limit was not evaluable due to insufficient patients.
Time Frame From first drug administration until 28 days after the end of third treatment course, up to 112 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Hide Arm/Group Description Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and if any diarrhea was experienced Common Terminology Criteria for Adverse Events (CTCAE Grade 1), 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2 mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects were orally administered with the starting dose of Afatinib Film-coated tablets 40 mg once daily - with possible dose reductions to 30 mg and 20 mg and 2 tablets of loperamide 2 mg daily (i.e., 4 mg daily) starting on Course 1 Day 1. If any diarrhea was experienced (CTCAE Grade 1) by subjects, 2 tablets of loperamide 2 mg were to be taken immediately, followed by 1 tablet of loperamide 2mg with every subsequent loose bowel movement until bowel movements ceased for 12 hours. Subjects who experienced no diarrhea during Course 1 were allowed to reduce the loperamide dose to 2 mg daily and subjects who experienced no diarrhea during the first two courses discontinued daily prophylactic loperamide at the end of Course 2.
All-Cause Mortality
Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Afatinib 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   10/18 (55.56%)   5/22 (22.73%) 
Gastrointestinal disorders     
Diarrhoea  1  3/18 (16.67%)  0/22 (0.00%) 
Diverticular perforation  1  0/18 (0.00%)  1/22 (4.55%) 
Gastritis  1  0/18 (0.00%)  1/22 (4.55%) 
Gastrointestinal haemorrhage  1  0/18 (0.00%)  1/22 (4.55%) 
Vomiting  1  1/18 (5.56%)  0/22 (0.00%) 
General disorders     
Asthenia  1  0/18 (0.00%)  1/22 (4.55%) 
Oedema peripheral  1  1/18 (5.56%)  0/22 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  1/18 (5.56%)  0/22 (0.00%) 
Infections and infestations     
Abscess limb  1  1/18 (5.56%)  0/22 (0.00%) 
Cellulitis  1  1/18 (5.56%)  0/22 (0.00%) 
Lung infection  1  1/18 (5.56%)  0/22 (0.00%) 
Sepsis  1  1/18 (5.56%)  0/22 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/18 (0.00%)  2/22 (9.09%) 
Hypoglycaemia  1  1/18 (5.56%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  0/18 (0.00%)  1/22 (4.55%) 
Psychiatric disorders     
Mental status changes  1  1/18 (5.56%)  0/22 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/18 (5.56%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/18 (5.56%)  0/22 (0.00%) 
Dyspnoea  1  1/18 (5.56%)  0/22 (0.00%) 
Pleural effusion  1  1/18 (5.56%)  0/22 (0.00%) 
Pulmonary embolism  1  1/18 (5.56%)  0/22 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/18 (5.56%)  0/22 (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 40 mg + Loperamide (Cohort 1) Afatinib 40 mg + Loperamide Prophylactic (Cohort 2)
Affected / at Risk (%) Affected / at Risk (%)
Total   18/18 (100.00%)   22/22 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  5/18 (27.78%)  1/22 (4.55%) 
Iron deficiency anaemia  1  1/18 (5.56%)  0/22 (0.00%) 
Cardiac disorders     
Pericardial effusion  1  1/18 (5.56%)  0/22 (0.00%) 
Ear and labyrinth disorders     
Tinnitus  1  1/18 (5.56%)  0/22 (0.00%) 
Eye disorders     
Diplopia  1  1/18 (5.56%)  0/22 (0.00%) 
Eye pruritus  1  2/18 (11.11%)  0/22 (0.00%) 
Eyelash hyperpigmentation  1  1/18 (5.56%)  0/22 (0.00%) 
Eyelid irritation  1  1/18 (5.56%)  0/22 (0.00%) 
Eyelid rash  1  1/18 (5.56%)  0/22 (0.00%) 
Growth of eyelashes  1  1/18 (5.56%)  0/22 (0.00%) 
Lacrimation increased  1  0/18 (0.00%)  2/22 (9.09%) 
Macular degeneration  1  1/18 (5.56%)  0/22 (0.00%) 
Ocular hyperaemia  1  1/18 (5.56%)  0/22 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/18 (11.11%)  2/22 (9.09%) 
Chapped lips  1  1/18 (5.56%)  0/22 (0.00%) 
Constipation  1  2/18 (11.11%)  11/22 (50.00%) 
Defaecation urgency  1  1/18 (5.56%)  0/22 (0.00%) 
Diarrhoea  1  16/18 (88.89%)  18/22 (81.82%) 
Dry mouth  1  0/18 (0.00%)  3/22 (13.64%) 
Dyspepsia  1  2/18 (11.11%)  0/22 (0.00%) 
Faeces hard  1  0/18 (0.00%)  2/22 (9.09%) 
Frequent bowel movements  1  3/18 (16.67%)  1/22 (4.55%) 
Gastrooesophageal reflux disease  1  1/18 (5.56%)  0/22 (0.00%) 
Haemorrhoids  1  1/18 (5.56%)  1/22 (4.55%) 
Lip blister  1  1/18 (5.56%)  0/22 (0.00%) 
Lip dry  1  2/18 (11.11%)  0/22 (0.00%) 
Lip pain  1  1/18 (5.56%)  0/22 (0.00%) 
Lip swelling  1  1/18 (5.56%)  0/22 (0.00%) 
Mouth ulceration  1  1/18 (5.56%)  0/22 (0.00%) 
Nausea  1  12/18 (66.67%)  8/22 (36.36%) 
Retching  1  1/18 (5.56%)  0/22 (0.00%) 
Stomatitis  1  7/18 (38.89%)  6/22 (27.27%) 
Vomiting  1  3/18 (16.67%)  3/22 (13.64%) 
General disorders     
Asthenia  1  2/18 (11.11%)  0/22 (0.00%) 
Chest pain  1  1/18 (5.56%)  0/22 (0.00%) 
Chills  1  1/18 (5.56%)  0/22 (0.00%) 
Fatigue  1  8/18 (44.44%)  5/22 (22.73%) 
Gait disturbance  1  1/18 (5.56%)  1/22 (4.55%) 
Mucosal inflammation  1  8/18 (44.44%)  3/22 (13.64%) 
Non-cardiac chest pain  1  2/18 (11.11%)  1/22 (4.55%) 
Oedema peripheral  1  4/18 (22.22%)  1/22 (4.55%) 
Pyrexia  1  2/18 (11.11%)  0/22 (0.00%) 
Xerosis  1  1/18 (5.56%)  2/22 (9.09%) 
Infections and infestations     
Candida infection  1  1/18 (5.56%)  1/22 (4.55%) 
Cellulitis  1  1/18 (5.56%)  1/22 (4.55%) 
Conjunctivitis  1  1/18 (5.56%)  0/22 (0.00%) 
Ear infection  1  1/18 (5.56%)  0/22 (0.00%) 
Folliculitis  1  1/18 (5.56%)  0/22 (0.00%) 
Gastroenteritis viral  1  1/18 (5.56%)  0/22 (0.00%) 
Localised infection  1  1/18 (5.56%)  0/22 (0.00%) 
Nail infection  1  1/18 (5.56%)  0/22 (0.00%) 
Nasopharyngitis  1  1/18 (5.56%)  0/22 (0.00%) 
Paronychia  1  2/18 (11.11%)  1/22 (4.55%) 
Pneumonia  1  1/18 (5.56%)  0/22 (0.00%) 
Rash pustular  1  0/18 (0.00%)  2/22 (9.09%) 
Rhinitis  1  1/18 (5.56%)  0/22 (0.00%) 
Upper respiratory tract infection  1  0/18 (0.00%)  2/22 (9.09%) 
Urinary tract infection  1  4/18 (22.22%)  2/22 (9.09%) 
Wound infection  1  1/18 (5.56%)  0/22 (0.00%) 
Injury, poisoning and procedural complications     
Animal bite  1  1/18 (5.56%)  0/22 (0.00%) 
Fall  1  3/18 (16.67%)  1/22 (4.55%) 
Incision site pain  1  1/18 (5.56%)  0/22 (0.00%) 
Laceration  1  1/18 (5.56%)  1/22 (4.55%) 
Skin abrasion  1  2/18 (11.11%)  0/22 (0.00%) 
Investigations     
Blood creatine phosphokinase increased  1  1/18 (5.56%)  0/22 (0.00%) 
Blood creatinine increased  1  1/18 (5.56%)  1/22 (4.55%) 
Blood magnesium decreased  1  2/18 (11.11%)  0/22 (0.00%) 
Blood phosphorus decreased  1  2/18 (11.11%)  0/22 (0.00%) 
Weight decreased  1  5/18 (27.78%)  2/22 (9.09%) 
Metabolism and nutrition disorders     
Decreased appetite  1  7/18 (38.89%)  4/22 (18.18%) 
Dehydration  1  7/18 (38.89%)  5/22 (22.73%) 
Gout  1  0/18 (0.00%)  2/22 (9.09%) 
Hypercalcaemia  1  1/18 (5.56%)  0/22 (0.00%) 
Hyperglycaemia  1  3/18 (16.67%)  1/22 (4.55%) 
Hypocalcaemia  1  0/18 (0.00%)  3/22 (13.64%) 
Hypoglycaemia  1  3/18 (16.67%)  0/22 (0.00%) 
Hypokalaemia  1  6/18 (33.33%)  3/22 (13.64%) 
Hypomagnesaemia  1  2/18 (11.11%)  1/22 (4.55%) 
Hyponatraemia  1  2/18 (11.11%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/18 (16.67%)  1/22 (4.55%) 
Back pain  1  4/18 (22.22%)  1/22 (4.55%) 
Chondrocalcinosis pyrophosphate  1  1/18 (5.56%)  0/22 (0.00%) 
Costochondritis  1  1/18 (5.56%)  0/22 (0.00%) 
Muscle spasms  1  2/18 (11.11%)  0/22 (0.00%) 
Muscular weakness  1  0/18 (0.00%)  2/22 (9.09%) 
Musculoskeletal chest pain  1  1/18 (5.56%)  1/22 (4.55%) 
Musculoskeletal pain  1  0/18 (0.00%)  2/22 (9.09%) 
Myalgia  1  1/18 (5.56%)  0/22 (0.00%) 
Pain in extremity  1  4/18 (22.22%)  2/22 (9.09%) 
Pain in jaw  1  1/18 (5.56%)  0/22 (0.00%) 
Nervous system disorders     
Balance disorder  1  2/18 (11.11%)  0/22 (0.00%) 
Dizziness  1  2/18 (11.11%)  2/22 (9.09%) 
Dysgeusia  1  4/18 (22.22%)  4/22 (18.18%) 
Headache  1  3/18 (16.67%)  1/22 (4.55%) 
Lethargy  1  1/18 (5.56%)  0/22 (0.00%) 
Memory impairment  1  2/18 (11.11%)  0/22 (0.00%) 
Neuropathy peripheral  1  2/18 (11.11%)  1/22 (4.55%) 
Peripheral sensory neuropathy  1  1/18 (5.56%)  0/22 (0.00%) 
Psychiatric disorders     
Anxiety  1  1/18 (5.56%)  1/22 (4.55%) 
Insomnia  1  1/18 (5.56%)  3/22 (13.64%) 
Renal and urinary disorders     
Proteinuria  1  1/18 (5.56%)  0/22 (0.00%) 
Renal failure  1  2/18 (11.11%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/18 (22.22%)  4/22 (18.18%) 
Dyspnoea  1  1/18 (5.56%)  4/22 (18.18%) 
Dyspnoea exertional  1  1/18 (5.56%)  0/22 (0.00%) 
Epistaxis  1  2/18 (11.11%)  2/22 (9.09%) 
Hiccups  1  1/18 (5.56%)  0/22 (0.00%) 
Nasal dryness  1  0/18 (0.00%)  3/22 (13.64%) 
Nasal inflammation  1  2/18 (11.11%)  0/22 (0.00%) 
Nasal ulcer  1  2/18 (11.11%)  1/22 (4.55%) 
Pleural effusion  1  1/18 (5.56%)  0/22 (0.00%) 
Sneezing  1  1/18 (5.56%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  4/18 (22.22%)  0/22 (0.00%) 
Dermatitis  1  1/18 (5.56%)  0/22 (0.00%) 
Dermatitis acneiform  1  7/18 (38.89%)  8/22 (36.36%) 
Dry skin  1  8/18 (44.44%)  4/22 (18.18%) 
Erythema  1  1/18 (5.56%)  0/22 (0.00%) 
Hair growth abnormal  1  1/18 (5.56%)  0/22 (0.00%) 
Hair texture abnormal  1  1/18 (5.56%)  0/22 (0.00%) 
Hyperhidrosis  1  1/18 (5.56%)  0/22 (0.00%) 
Nail discolouration  1  1/18 (5.56%)  0/22 (0.00%) 
Nail disorder  1  2/18 (11.11%)  1/22 (4.55%) 
Nail toxicity  1  2/18 (11.11%)  0/22 (0.00%) 
Night sweats  1  3/18 (16.67%)  0/22 (0.00%) 
Onychoclasis  1  1/18 (5.56%)  0/22 (0.00%) 
Onychomadesis  1  2/18 (11.11%)  0/22 (0.00%) 
Pain of skin  1  1/18 (5.56%)  0/22 (0.00%) 
Pruritus  1  4/18 (22.22%)  3/22 (13.64%) 
Rash  1  7/18 (38.89%)  4/22 (18.18%) 
Rash macular  1  1/18 (5.56%)  0/22 (0.00%) 
Rash maculo-papular  1  2/18 (11.11%)  2/22 (9.09%) 
Rash pruritic  1  2/18 (11.11%)  0/22 (0.00%) 
Skin exfoliation  1  1/18 (5.56%)  0/22 (0.00%) 
Skin fissures  1  1/18 (5.56%)  3/22 (13.64%) 
Skin irritation  1  1/18 (5.56%)  0/22 (0.00%) 
Vascular disorders     
Hot flush  1  1/18 (5.56%)  0/22 (0.00%) 
Hypertension  1  1/18 (5.56%)  1/22 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
In this study, Nine patients experienced diarrhea episodes that were not managed according to the protocol specified afatinib treatment interruptions and dose reductions. No patients were excluded from the primary analysis.
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
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: NCT01814553     History of Changes
Other Study ID Numbers: 1200.167
First Submitted: March 4, 2013
First Posted: March 20, 2013
Results First Submitted: July 1, 2016
Results First Posted: October 31, 2016
Last Update Posted: October 31, 2016