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Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO (ARCHER 1042)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01465802
Recruitment Status : Completed
First Posted : November 6, 2011
Results First Posted : August 17, 2016
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Small Cell Lung Cancer (NSCLC)
Interventions Drug: Dacomitinib
Drug: Doxycycline
Drug: Probiotic
Drug: Alclometasone cream
Enrollment 236
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description Open-label dacomitinib 45 milligram (mg) tablets orally (PO) taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05 percent (%) applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Period Title: Overall Study
Started 66 66 7 67 [1] 25
Completed 33 42 7 38 13
Not Completed 33 24 0 29 12
Reason Not Completed
Study terminated by sponsor             1             0             0             1             7
Withdrawal by Subject             7             7             0             8             1
Lost to Follow-up             1             1             0             0             0
Reason not specified             9             4             0             10             2
Death             15             12             0             10             2
[1]
An additional 5 participants were enrolled in Cohort II but not treated.
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg) Total
Hide Arm/Group Description Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal. Total of all reporting groups
Overall Number of Baseline Participants 66 66 7 67 25 231
Hide Baseline Analysis Population Description
As Treated Population - included all participants who received at least 1 dose of study treatment assigned at enrollment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 66 participants 7 participants 67 participants 25 participants 231 participants
65.0  (10.38) 64.4  (10.55) 61.3  (7.67) 66.0  (9.63) 64.2  (14.29) 64.9  (10.59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 66 participants 7 participants 67 participants 25 participants 231 participants
Female
38
  57.6%
27
  40.9%
2
  28.6%
24
  35.8%
18
  72.0%
109
  47.2%
Male
28
  42.4%
39
  59.1%
5
  71.4%
43
  64.2%
7
  28.0%
122
  52.8%
1.Primary Outcome
Title Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
Hide Description

SDAEI of all causality and all grades were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.

95% confidence interval (CI) calculated using exact method based on binomial distribution.

After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 1 was not conducted in Cohort I Arm C.

Time Frame First 8 Weeks of Treatment
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Hide Analysis Population Description
Evaluable Population - included all participants who received the study treatment assigned at enrollment, but did not discontinue dacomitinib treatment less than 6 weeks from first dosing due to either disease progression or death.
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 58 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
79.3
(66.6 to 88.8)
75.0
(61.6 to 85.6)
2.Primary Outcome
Title Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
Hide Description

SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. Adverse events (AEs) were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 4.0).

95% CI calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 2 was not conducted in Cohort I Arm C.

Time Frame First 8 Weeks of Treatment
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Hide Analysis Population Description
Evaluable Population
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 58 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
46.6
(33.3 to 60.1)
23.2
(13.0 to 36.4)
3.Primary Outcome
Title Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I
Hide Description

Patient Reported Outcomes (PROs) of Health Related Quality of Life (HRQoL) & disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions & functioning. Individual scaled scores & total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if greater than (>) 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.

Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.

Time Frame First 8 Weeks of Treatment
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Hide Analysis Population Description
PRO Skindex Analysis Population: participants that met primary endpoint analysis & Skindex specific criteria: a) Skindex completion criteria (as above) for initial visit & end of Cycle 2 or EoT visit; b) Skindex completion criteria for at least 5 of 6 visits between initial visit & end of Cycle 2 visit. n = number of participants completing scale.
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 42 42 4
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Symptoms: Cycle 1 Day 8 (n=41, 42, 4) 2.3  (10.12) -1.1  (10.91) 9.4  (14.18)
Symptoms: Cycle 1 Day 15 (n=41, 42, 3) 21.4  (30.98) 5.0  (19.82) 30.6  (42.56)
Symptoms: Cycle 1 Day 22 (n=42, 40, 4) 18.0  (25.76) 6.8  (20.45) 32.3  (25.54)
Symptoms: Cycle 2 Day 1 (n=41, 42, 4) 14.7  (23.74) 6.3  (15.38) 14.6  (18.48)
Symptoms: Cycle 2 Day 8 (n=42, 39, 4) 17.8  (26.78) 9.8  (20.00) 13.5  (19.36)
Symptoms: Cycle 2 Day 15 (n=37, 40, 4) 16.6  (21.10) 9.2  (19.54) 19.8  (28.74)
Symptoms: Cycle 2 Day 22 (n=35, 39, 4) 15.4  (22.34) 12.9  (22.72) 14.6  (15.40)
Symptoms: EoT (n=7, 3, 0) 13.1  (32.85) 16.7  (19.09) NA [1]   (NA)
Emotion: Cycle 1 Day 8 (n=41, 42, 4) 3.7  (21.08) -2.5  (12.11) 7.3  (14.68)
Emotion: Cycle 1 Day 15 (n=41, 42, 3) 20.7  (28.51) 2.9  (17.14) 29.8  (45.03)
Emotion: Cycle 1 Day 22 (n=42, 40, 4) 17.7  (27.67) 3.7  (16.07) 37.7  (32.44)
Emotion: Cycle 2 Day 1 (n=41, 42, 4) 15.6  (25.15) 6.5  (15.25) 23.4  (30.15)
Emotion: Cycle 2 Day 8 (n=42, 39, 4) 15.1  (25.55) 6.3  (17.28) 21.6  (35.76)
Emotion: Cycle 2 Day 15 (n=37, 40, 4) 13.0  (22.70) 8.4  (20.20) 21.0  (40.49)
Emotion: Cycle 2 Day 22 (n=35, 39, 4) 14.8  (25.91) 12.0  (23.73) 10.9  (17.39)
Emotion: EoT (n=7, 3, 0) 9.9  (21.27) 22.2  (21.34) NA [2]   (NA)
Functioning: Cycle 1 Day 8 (n=41, 42, 4) 3.1  (17.60) -1.2  (5.50) -0.8  (1.67)
Functioning: Cycle 1 Day 15 (n=41, 42, 3) 11.1  (21.41) 0.6  (7.47) 24.4  (42.34)
Functioning: Cycle 1 Day 22 (n=42, 40, 4) 11.7  (21.68) 1.9  (8.86) 33.3  (31.39)
Functioning: Cycle 2 Day 1 (n=41, 42, 4) 8.5  (21.53) 2.1  (7.72) 20.0  (21.26)
Functioning: Cycle 2 Day 8 (n=42, 39, 4) 7.0  (18.51) 2.4  (9.52) 12.5  (20.79)
Functioning: Cycle 2 Day 15 (n=37, 40, 4) 8.3  (22.20) 2.7  (10.58) 13.3  (22.44)
Functioning: Cycle 2 Day 22 (n=35, 39, 4) 7.8  (22.32) 5.4  (13.78) 14.2  (20.44)
Functioning: EoT (n=7, 3, 0) 8.6  (11.84) 14.4  (25.02) NA [2]   (NA)
Total: Cycle 1 Day 8 (n=41, 42, 4) 3.2  (15.91) -1.7  (8.07) 5.3  (9.36)
Total: Cycle 1 Day 15 (n=41, 42, 3) 17.9  (25.09) 2.7  (13.08) 28.4  (43.52)
Total: Cycle 1 Day 22 (n=42, 40, 4) 15.9  (23.39) 4.0  (13.33) 35.0  (29.97)
Total: Cycle 2 Day 1 (n=41, 42, 4) 13.1  (20.74) 5.1  (11.65) 20.2  (21.75)
Total: Cycle 2 Day 8 (n=42, 39, 4) 13.2  (21.17) 6.0  (13.49) 16.8  (24.54)
Total: Cycle 2 Day 15 (n=37, 40, 4) 12.4  (20.39) 6.8  (14.84) 18.4  (31.50)
Total: Cycle 2 Day 22 (n=35, 39, 4) 12.7  (21.24) 10.1  (18.36) 12.9  (17.22)
Total: EoT (n=7, 3, 0) 10.3  (18.79) 18.4  (18.64) NA [2]   (NA)
[1]
NA = not applicable. The number of participants completing the scale at this timepoint was 0.
[2]
The number of participants completing the scale at this timepoint was 0.
4.Primary Outcome
Title Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Hide Description

Diarrhea AEs of all causality, all grade and Grade ≥2 were evaluated in participants in Cohort II. AEs were graded for severity using the NCI-CTCAE, Version 4.0.

95% CI calculated using exact method based on binomial distribution.

Time Frame First 8 Weeks of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population
Arm/Group Title Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
All Causality, All Grade
83.1
(71.0 to 91.6)
All Causality, Grade ≥2
39.0
(26.5 to 52.6)
5.Primary Outcome
Title Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II
Hide Description

Diarrhea severity was assessed using the modified-OMDQ. This questionnaire is comprised of 6 questions in total; however, only two items relate to diarrhea symptoms (item 5 and item 6). Symptoms scores were developed for both the full questionnaire and for the diarrhea-only questions for each completed survey. Mucositis questions were transformed to a score range of 0 to 10. Increasing OMDQ values are associated with greater symptom burden.

Modified OMDQ completion criteria were defined as completion of all 4 questions (questions 2, 4, 5 and 6).

M/T = mouth and throat.

Time Frame Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
PRO Modified OMDQ Analysis Population; participants meeting primary endpoint analysis & modified OMDQ specific criteria: a) Modified OMDQ completion criteria for initial visit & end of Cycle 2 or EoT visit; b) Completion criteria for at least 5 of 6 visits between initial & end of Cycle 2 visit. n = number of participants completing scale.
Arm/Group Title Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: Score on a scale
M/T Soreness Categories: Cycle 1 Day 8 (n=37) 0.8  (2.05)
M/T Soreness Categories: Cycle 1 Day 15 (n=37) 2.5  (3.12)
M/T Soreness Categories: Cycle 1 Day 22 (n=37) 2.6  (2.97)
M/T Soreness Categories: Cycle 2 Day 1 (n=37) 2.5  (2.43)
M/T Soreness Categories: Cycle 2 Day 8 (n=35) 1.9  (2.30)
M/T Soreness Categories: Cycle 2 Day 15 (n=36) 1.7  (1.97)
M/T Soreness Categories: Cycle 2 Day 22 (n=27) 1.6  (1.85)
M/T Soreness Categories: Cycle 3 Day 1 (n=19) 2.1  (2.09)
M/T Soreness Categories: Cycle 4 Day 1 (n=13) 1.7  (2.14)
M/T Soreness Categories: Cycle 5 Day 1 (n=10) 1.0  (1.29)
M/T Soreness Categories: Cycle 6 Day 1 (n=8) 0.3  (0.88)
M/T Soreness Categories: EoT (n=30) 1.4  (2.34)
M/T Soreness Categories: Follow-up (n=22) 0.3  (2.48)
M/T Soreness Scale: Cycle 1 Day 8 (n=37) 1.0  (2.00)
M/T Soreness Scale: Cycle 1 Day 15 (n=37) 2.5  (3.00)
M/T Soreness Scale: Cycle 1 Day 22 (n=37) 2.2  (2.51)
M/T Soreness Scale: Cycle 2 Day 1 (n=37) 2.2  (2.28)
M/T Soreness Scale: Cycle 2 Day 8 (n=35) 1.7  (1.97)
M/T Soreness Scale: Cycle 2 Day 15 (n=36) 1.6  (1.83)
M/T Soreness Scale: Cycle 2 Day 22 (n=27) 1.9  (2.45)
M/T Soreness Scale: Cycle 3 Day 1 (n=19) 2.2  (2.81)
M/T Soreness Scale: Cycle 4 Day 1 (n=13) 1.6  (2.81)
M/T Soreness Scale: Cycle 5 Day 1 (n=10) 1.0  (1.76)
M/T Soreness Scale: Cycle 6 Day 1 (n=8) 0.1  (0.35)
M/T Soreness Scale: EoT (n=30) 1.3  (1.78)
M/T Soreness Scale: Follow-up (n=22) 0.5  (1.68)
Diarrhea Categories: Cycle 1 Day 8 (n=37) 2.1  (2.67)
Diarrhea Categories: Cycle 1 Day 15 (n=37) 3.2  (2.94)
Diarrhea Categories: Cycle 1 Day 22 (n=36) 3.9  (3.19)
Diarrhea Categories: Cycle 2 Day 1 (n=37) 3.0  (2.83)
Diarrhea Categories: Cycle 2 Day 8 (n=34) 2.2  (3.00)
Diarrhea Categories: Cycle 2 Day 15 (n=36) 2.1  (3.13)
Diarrhea Categories: Cycle 2 Day 22 (n=27) 2.7  (3.10)
Diarrhea Categories: Cycle 3 Day 1 (n=19) 2.8  (2.75)
Diarrhea Categories: Cycle 4 Day 1 (n=13) 2.3  (3.14)
Diarrhea Categories: Cycle 5 Day 1 (n=10) 3.8  (3.39)
Diarrhea Categories: Cycle 6 Day 1 (n=8) 1.9  (2.22)
Diarrhea Categories: EoT (n=30) 1.9  (3.39)
Diarrhea Categories: Follow-up (n=22) -0.1  (0.94)
Diarrhea Scale: Cycle 1 Day 8 (n=37) 1.2  (1.89)
Diarrhea Scale: Cycle 1 Day 15 (n=37) 2.4  (2.55)
Diarrhea Scale: Cycle 1 Day 22 (n=36) 3.0  (2.96)
Diarrhea Scale: Cycle 2 Day 1 (n=37) 2.5  (2.61)
Diarrhea Scale: Cycle 2 Day 8 (n=34) 2.0  (2.75)
Diarrhea Scale: Cycle 2 Day 15 (n=35) 1.7  (2.71)
Diarrhea Scale: Cycle 2 Day 22 (n=27) 2.0  (2.16)
Diarrhea Scale: Cycle 3 Day 1 (n=19) 2.4  (2.34)
Diarrhea Scale: Cycle 4 Day 1 (n=13) 1.8  (2.13)
Diarrhea Scale: Cycle 5 Day 1 (n=10) 2.7  (2.31)
Diarrhea Scale: Cycle 6 Day 1 (n=8) 1.5  (1.93)
Diarrhea Scale: EoT (n=30) 1.6  (2.87)
Diarrhea Scale: Follow-up (n=22) -0.1  (0.71)
6.Primary Outcome
Title Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II
Hide Description

SDAEI of all causality and all grades were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.

95% CI calculated using exact method based on binomial distribution.

Time Frame First 8 Weeks of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Population
Arm/Group Title Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
79.7
(67.2 to 89.0)
7.Primary Outcome
Title Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Hide Description

SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. AEs were graded for severity using the NCI-CTCAE, Version 4.0.

95% CI calculated using exact method based on binomial distribution.

Time Frame First 8 Weeks of Treatment
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Evaluable Population
Arm/Group Title Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)
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Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 59
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
35.6
(23.6 to 49.1)
8.Primary Outcome
Title Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II
Hide Description

PROs of HRQoL and disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions & functioning. Individual scaled scores & total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if > 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.

Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.

Time Frame Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
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PRO Skindex Analysis Population
Arm/Group Title Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Symptoms: Cycle 1 Day 8 (n=40) 0.1  (8.31)
Symptoms: Cycle 1 Day 15 (n=40) 11.4  (21.25)
Symptoms: Cycle 1 Day 22 (n=40) 11.4  (18.17)
Symptoms: Cycle 2 Day 1 (n=40) 11.4  (19.84)
Symptoms: Cycle 2 Day 8 (n=38) 13.5  (20.88)
Symptoms: Cycle 2 Day 15 (n=38) 14.7  (17.83)
Symptoms: Cycle 2 Day 22 (n=30) 13.6  (16.30)
Symptoms: Cycle 3 Day 1 (n=21) 12.7  (19.56)
Symptoms: Cycle 4 Day 1 (n=15) 11.9  (18.69)
Symptoms: Cycle 5 Day 1 (n=11) 8.0  (22.24)
Symptoms: Cycle 6 Day 1 (n=8) 12.0  (32.15)
Symptoms: EoT (n=33) 10.4  (21.33)
Symptoms: Follow-up (n=23) 7.1  (23.15)
Emotion: Cycle 1 Day 8 (n=40) 1.0  (11.79)
Emotion: Cycle 1 Day 15 (n=40) 8.7  (23.57)
Emotion: Cycle 1 Day 22 (n=40) 12.3  (24.63)
Emotion: Cycle 2 Day 1 (n=40) 10.2  (21.36)
Emotion: Cycle 2 Day 8 (n=38) 10.3  (21.77)
Emotion: Cycle 2 Day 15 (n=37) 13.5  (17.10)
Emotion: Cycle 2 Day 22 (n= 30) 12.6  (19.86)
Emotion: Cycle 3 Day 1 (n=21) 11.0  (17.97)
Emotion: Cycle 4 Day 1 (n=14) 11.5  (14.65)
Emotion: Cycle 5 Day 1 (n=11) 7.8  (21.43)
Emotion: Cycle 6 Day 1 (n=8) 6.8  (22.67)
Emotion: EoT (n=33) 8.5  (23.38)
Emotion: Follow-up (n=23) 7.1  (22.74)
Functioning: Cycle 1 Day 8 (n=40) 0.5  (3.58)
Functioning: Cycle 1 Day 15 (n=40) 4.3  (13.34)
Functioning: Cycle 1 Day 22 (n=40) 8.8  (17.55)
Functioning: Cycle 2 Day 1 (n=40) 7.3  (15.25)
Functioning: Cycle 2 Day 8 (n=38) 6.2  (15.33)
Functioning: Cycle 2 Day 15 (n=38) 7.0  (11.75)
Functioning: Cycle 2 Day 22 (n=30) 7.2  (10.06)
Functioning: Cycle 3 Day 1 (n=21) 5.9  (8.09)
Functioning: Cycle 4 Day 1 (n=15) 6.9  (10.12)
Functioning: Cycle 5 Day 1 (n=11) 5.5  (12.93)
Functioning: Cycle 6 Day 1 (n=8) 7.1  (15.58)
Functioning: EoT (n=33) 7.7  (17.35)
Functioning: Follow-up (n=23) 5.4  (18.55)
Total: Cycle 1 Day 8 (n=40) 0.6  (6.83)
Total: Cycle 1 Day 15 (n=40) 8.0  (18.73)
Total: Cycle 1 Day 22 (n=40) 11.0  (19.59)
Total: Cycle 2 Day 1 (n=40) 9.6  (17.38)
Total: Cycle 2 Day 8 (n=38) 9.9  (17.79)
Total: Cycle 2 Day 15 (n=38) 11.8  (14.13)
Total: Cycle 2 Day 22 (n=30) 11.2  (14.14)
Total: Cycle 3 Day 1 (n=21) 9.8  (14.11)
Total: Cycle 4 Day 1 (n=15) 10.2  (12.49)
Total: Cycle 5 Day 1 (n=11) 7.1  (18.60)
Total: Cycle 6 Day 1 (n=8) 8.2  (22.43)
Total: EoT (n=33) 8.7  (19.74)
Total: Follow-up (n=23) 6.6  (20.52)
9.Primary Outcome
Title Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Hide Description

AUC0-24 is the area under the plasma concentration-time curve (AUC) from time 0 to 24 hours post-dose. AUC0-120 is the AUC from time 0 to 120 hours post-dose. AUC was calculated by the linear trapezoidal method using a non-compartmental pharmacokinetic (PK) analysis.

ng*hr/mL = nanogram hours per milliliter

Time Frame Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
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Dose-Compliant participants only. Participants were considered dose-compliant when they received all planned doses at the same dose level right before sample collection.
Arm/Group Title Cohort III (Dacomitinib 45 mg)
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Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Dacomitinib AUC0-24
1712.88
(35%)
Dacomitinib AUC0-120
5743.60
(32%)
PF-05199265 AUC0-24
184.62
(139%)
PF-05199265 AUC0-120
742.32
(129%)
10.Primary Outcome
Title Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Hide Description Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter
Time Frame Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
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Hide Analysis Population Description
Dose-Compliant participants only. Participants were considered dose-compliant when they received all planned doses at the same dose level right before sample collection.
Arm/Group Title Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Dacomitinib Cmax
79.68
(36%)
PF-05199265 Cmax
8.5176
(137%)
11.Primary Outcome
Title Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Hide Description Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
Time Frame Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
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Hide Analysis Population Description
Dose-Compliant participants only. Participants were considered dose-compliant when they received all planned doses at the same dose level right before sample collection.
Arm/Group Title Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 23
Median (Full Range)
Unit of Measure: hours (hr)
Dacomitinib Tmax
5.850
(0 to 24.30)
PF-05199265 Tmax
5.980
(0 to 24.30)
12.Secondary Outcome
Title Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III
Hide Description Medications used concomitantly for SDAEIs, diarrhea and mucositis were evaluated for all participants who received dacomitinib on a continuous basis with a preemptive prophylactic (Cohorts I and II) or as an interrupted dosing regimen (Cohort III).
Time Frame Screening to the Post-Teatment Follow-Up Visit (at least 28 days and no more than 35 days after the end of dacomitinib treatment due to progression of disease, intolerance to dacomitinib treatment, or participant withdrawal)
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As Treated Population
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 66 66 7 67 25
Measure Type: Number
Unit of Measure: Percentage of Participants
Any Concomitant Drug 69.7 60.6 85.7 82.1 88.0
Any Non-Drug Treatment 16.7 16.7 42.9 20.9 44.0
13.Secondary Outcome
Title Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Hide Description AUCtau was the AUC from time 0 to the end of the dosing interval, where the dosing interval was 24 hours. AUCtau was calculated by the linear/log trapezoidal method using a non-compartmental PK analysis.
Time Frame Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
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Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection.

Number of participants analyzed is the number of participants contributing to the summary statistics.

Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 27 27 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Dacomitinib AUC0-tau
1801.96
(59%)
1869.23
(37%)
1412.42
(63%)
PF-05199265 AUC0-tau
164.520
(89%)
112.306
(139%)
366.933
(107%)
14.Secondary Outcome
Title Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Hide Description Cmax was obtained from direct inspection of the data.
Time Frame Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
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Hide Analysis Population Description

Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection.

Number of participants analyzed is the number of participants contributing to the summary statistics.

Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 31 27 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Dacomitinib Cmax
88.15
(57%)
89.79
(36%)
98.08
(89%)
PF-05199265 Cmax
7.7426
(80%)
5.2901
(141%)
8.8545
(260%)
15.Secondary Outcome
Title Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Hide Description Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
Time Frame Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description

Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection.

Number of participants analyzed is the number of participants contributing to the summary statistics.

Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 31 27 3
Median (Full Range)
Unit of Measure: hr
Dacomitinib Tmax
4.000
(0 to 24.00)
6.000
(0 to 24.30)
6.580
(4.02 to 22.20)
PF-05199265 Tmax
4.050
(0 to 24.10)
4.020
(0 to 24.30)
6.580
(0 to 22.20)
16.Secondary Outcome
Title Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I
Hide Description CL/F was calculated as dose/AUCtau.
Time Frame Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
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Hide Analysis Population Description

Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection.

Number of participants analyzed is the number of participants contributing to the summary statistics.

Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Overall Number of Participants Analyzed 31 27 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters per hour
29.94
(85%)
24.07
(37%)
34.24
(45%)
17.Secondary Outcome
Title Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III
Hide Description

Ctrough was the pre-dose plasma concentration of dacomitinib at steady state obtained from direct inspection of the data.

Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.

Time Frame Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Hide Outcome Measure Data
Hide Analysis Population Description
Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection in Cohorts I, II and III.
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 34 32 5 15 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 3 Day 1 (n=13, 15, 3, 14, 15)
65.477
(50%)
65.063
(55%)
56.212
(46%)
66.338
(58%)
55.780
(40%)
Cycle 4 Day 1 (n=8, 7, 2, 5, 13)
61.592
(36%)
67.109
(29%)
65.466
(49%)
71.116
(49%)
55.644
(42%)
Cycle 5 Day 1 (n=3, 6, 2, 3, 12)
89.970
(38%)
68.012
(39%)
69.649
(63%)
66.082
(33%)
53.116
(44%)
Cycle 6 Day 1 (n=2, 5, 1, 2, 10)
15.578
(1208%)
72.856
(47%)
46.000 [1] 
(NA%)
9.201
(3760%)
52.603
(52%)
Cycle 7 Day 1 (n=2, 1, 1, 1, 8)
59.086
(47%)
40.900 [1] 
(NA%)
59.900 [1] 
(NA%)
42.600 [1] 
(NA%)
55.685
(21%)
Cycle 8 Day 1 (n=2, 2, 1, 2, 8)
61.430
(90%)
58.988
(31%)
47.00 [1] 
(NA%)
64.296
(35%)
51.559
(24%)
Cycle 9 Day 1 (n=2, 2, 1, 2, 6)
64.747
(72%)
58.928
(31%)
46.000 [1] 
(NA%)
64.115
(30%)
44.865
(50%)
Cycle 10 Day 1 (n=1, 2, 1, 2, 4)
51.400 [1] 
(NA%)
54.041
(48%)
58.800 [1] 
(NA%)
71.695
(26%)
55.362
(32%)
[1]
Geometric mean coefficient of variation is not calculable as n=1.
18.Secondary Outcome
Title Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III
Hide Description

Ctrough was the pre-dose plasma concentration of the dacomitinib metabolite PF-05199265 at steady state obtained from direct inspection of the data.

Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.

Time Frame Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Hide Outcome Measure Data
Hide Analysis Population Description
Dose-Compliant participants only. Participants were considered dose-compliant when they received at least 14 consecutive doses at the same dose level right before sample collection in Cohorts I, II and III.
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description:
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment).
Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
Overall Number of Participants Analyzed 34 32 5 15 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 3 Day 1 (n=13, 15, 3, 14, 15)
6.988
(60%)
4.653
(133%)
10.220
(11%)
7.814
(59%)
9.967
(149%)
Cycle 4 Day 1 (n=8, 7, 2, 5, 13)
5.555
(71%)
5.271
(242%)
8.522
(15%)
6.848
(82%)
11.759
(113%)
Cycle 5 Day 1 (n=3, 6, 2, 3, 12)
4.356
(55%)
4.989
(58%)
8.522
(10%)
5.850
(115%)
10.510
(124%)
Cycle 6 Day 1 (n=2, 5, 1, 2, 10)
5.020
(70%)
6.523
(123%)
8.150 [1] 
(NA%)
1.261
(937%)
7.844
(125%)
Cycle 7 Day 1 (n=2, 1, 1, 1, 8)
4.850
(49%)
23.900 [1] 
(NA%)
8.560 [1] 
(NA%)
6.680 [1] 
(NA%)
8.203
(105%)
Cycle 8 Day 1 (n=2, 2, 1, 2, 8)
5.349
(54%)
6.085
(476%)
10.100 [1] 
(NA%)
10.844
(38%)
8.205
(117%)
Cycle 9 Day 1 (n=2, 2, 1, 2, 6)
4.271
(34%)
6.448
(612%)
9.720 [1] 
(NA%)
9.159
(58%)
6.963
(88%)
Cycle 10 Day 1 (n=1, 2, 1, 2, 4)
3.460 [1] 
(NA%)
6.892
(305%)
10.700 [1] 
(NA%)
9.442
(26%)
6.364
(154%)
[1]
Geometric mean coefficient of variation is not calculable as n=1.
Time Frame Reported AEs and serious AEs (SAEs) included events starting from the time participant had taken at least 1 dose of study drug through and including 28 calendar days after the last dose of study drug, with a median of 12 weeks.
Adverse Event Reporting Description The same event may appear as both an AE & SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant & non-serious in another, or 1 participant may have experienced both a serious & non-serious event during the study. Summaries inclusive of events occurring after start of treatment.
 
Arm/Group Title Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Hide Arm/Group Description Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline placebo capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS single-blind (participant blinded) doxycycline 100 mg capsules PO taken twice daily for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO taken once daily until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal PLUS open-label VSL#3 probiotic 4 capsules PO taken once daily or 1 sachet PO taken once daily starting on either Days -7, -6, -5 or -4 per site/participant preference, and continuing through Cycle 1 Day 28 (for a total of up to 5 weeks [range of 32 to 35 days]) PLUS open-label topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks (prophylactic treatment). Open-label dacomitinib 45 mg tablets PO, taken once daily Cycle 1 Day 1 through and including Cycle 1 Day 10; no dacomitinib was taken on Cycle 1 Days 11, 12, 13 and 14; resumption of dacomitinib 45 mg PO once daily taken continuously from Cycle 1 Day 15 onwards until progression of disease, intolerance to dacomitinib treatment, or participant withdrawal.
All-Cause Mortality
Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/66 (37.88%)   27/66 (40.91%)   3/7 (42.86%)   22/67 (32.84%)   6/25 (24.00%) 
Blood and lymphatic system disorders           
Anaemia  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  1/25 (4.00%) 
Febrile neutropenia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Leukocytosis  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pancytopenia  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Cardiac disorders           
Cardiac arrest  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Cardiac tamponade  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Cardio-respiratory arrest  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Cardiogenic shock  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Myocardial infarction  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pericardial effusion  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Supraventricular tachycardia  1  0/66 (0.00%)  2/66 (3.03%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Eye disorders           
Diplopia  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Constipation  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Diarrhoea  1  1/66 (1.52%)  2/66 (3.03%)  1/7 (14.29%)  1/67 (1.49%)  1/25 (4.00%) 
Duodenal ulcer perforation  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Gastrointestinal haemorrhage  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Intestinal obstruction  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Intra-abdominal haemorrhage  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Nausea  1  0/66 (0.00%)  4/66 (6.06%)  0/7 (0.00%)  1/67 (1.49%)  1/25 (4.00%) 
Small intestinal obstruction  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Vomiting  1  0/66 (0.00%)  3/66 (4.55%)  0/7 (0.00%)  2/67 (2.99%)  1/25 (4.00%) 
General disorders           
Asthenia  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Chest pain  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Disease progression  1  7/66 (10.61%)  7/66 (10.61%)  0/7 (0.00%)  8/67 (11.94%)  1/25 (4.00%) 
Mucosal inflammation  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Non-cardiac chest pain  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Pain  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Pyrexia  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Infections and infestations           
Acute sinusitis  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Cholecystitis infective  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Clostridium difficile colitis  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Enterocolitis infectious  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Gastroenteritis  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Osteomyelitis  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pneumonia  1  2/66 (3.03%)  0/66 (0.00%)  1/7 (14.29%)  5/67 (7.46%)  1/25 (4.00%) 
Septic shock  1  2/66 (3.03%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Injury, poisoning and procedural complications           
Fall  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Femoral neck fracture  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Femur fracture  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Rib fracture  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Spinal fracture  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Toxicity to various agents  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Investigations           
Blood creatinine increased  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Platelet count decreased  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  1/25 (4.00%) 
Weight decreased  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  5/66 (7.58%)  3/66 (4.55%)  0/7 (0.00%)  1/67 (1.49%)  1/25 (4.00%) 
Electrolyte imbalance  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Hypokalaemia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  1/25 (4.00%) 
Metabolic acidosis  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Metabolic alkalosis  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Back pain  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Lung cancer metastatic  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Malignant pleural effusion  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Non-small cell lung cancer metastatic  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pancreatic carcinoma  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Nervous system disorders           
Aphasia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Cerebral haemorrhage  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Cerebral infarction  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Cerebrovascular accident  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Transient ischaemic attack  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Renal and urinary disorders           
Acute kidney injury  1  3/66 (4.55%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Haematuria  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Hydronephrosis  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Renal impairment  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Dyspnoea  1  1/66 (1.52%)  2/66 (3.03%)  1/7 (14.29%)  1/67 (1.49%)  1/25 (4.00%) 
Hypoxia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Pleural effusion  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pleuritic pain  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pneumonitis  1  0/66 (0.00%)  2/66 (3.03%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Pneumothorax  1  2/66 (3.03%)  2/66 (3.03%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Pulmonary embolism  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Respiratory distress  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Respiratory failure  1  0/66 (0.00%)  2/66 (3.03%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Skin and subcutaneous tissue disorders           
Perivascular dermatitis  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Subcutaneous emphysema  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Embolism  1  0/66 (0.00%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  1/25 (4.00%) 
Hypotension  1  0/66 (0.00%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Hypovolaemic shock  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  0/25 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) Cohort III (Dacomitinib 45 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   65/66 (98.48%)   66/66 (100.00%)   7/7 (100.00%)   64/67 (95.52%)   25/25 (100.00%) 
Blood and lymphatic system disorders           
Anaemia  1  10/66 (15.15%)  7/66 (10.61%)  3/7 (42.86%)  5/67 (7.46%)  3/25 (12.00%) 
Cardiac disorders           
Tachycardia  1  1/66 (1.52%)  4/66 (6.06%)  0/7 (0.00%)  3/67 (4.48%)  0/25 (0.00%) 
Ear and labyrinth disorders           
Deafness  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Tinnitus  1  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Eye disorders           
Dry eye  1  5/66 (7.58%)  4/66 (6.06%)  0/7 (0.00%)  2/67 (2.99%)  3/25 (12.00%) 
Eye pain  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  2/25 (8.00%) 
Ocular hyperaemia  1  2/66 (3.03%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  2/25 (8.00%) 
Vision blurred  1  0/66 (0.00%)  1/66 (1.52%)  2/7 (28.57%)  0/67 (0.00%)  1/25 (4.00%) 
Gastrointestinal disorders           
Abdominal distension  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  2/67 (2.99%)  2/25 (8.00%) 
Abdominal pain  1  7/66 (10.61%)  7/66 (10.61%)  0/7 (0.00%)  3/67 (4.48%)  3/25 (12.00%) 
Abdominal pain upper  1  4/66 (6.06%)  3/66 (4.55%)  0/7 (0.00%)  2/67 (2.99%)  2/25 (8.00%) 
Cheilitis  1  3/66 (4.55%)  1/66 (1.52%)  1/7 (14.29%)  3/67 (4.48%)  1/25 (4.00%) 
Constipation  1  9/66 (13.64%)  14/66 (21.21%)  2/7 (28.57%)  8/67 (11.94%)  3/25 (12.00%) 
Diarrhoea  1  54/66 (81.82%)  52/66 (78.79%)  7/7 (100.00%)  54/67 (80.60%)  23/25 (92.00%) 
Dry mouth  1  4/66 (6.06%)  5/66 (7.58%)  1/7 (14.29%)  4/67 (5.97%)  6/25 (24.00%) 
Dyspepsia  1  3/66 (4.55%)  10/66 (15.15%)  0/7 (0.00%)  2/67 (2.99%)  3/25 (12.00%) 
Food poisoning  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Gastritis  1  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Glossodynia  1  0/66 (0.00%)  4/66 (6.06%)  0/7 (0.00%)  1/67 (1.49%)  0/25 (0.00%) 
Haemorrhoids  1  0/66 (0.00%)  1/66 (1.52%)  0/7 (0.00%)  1/67 (1.49%)  2/25 (8.00%) 
Lip swelling  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Nausea  1  28/66 (42.42%)  31/66 (46.97%)  2/7 (28.57%)  20/67 (29.85%)  4/25 (16.00%) 
Oesophagitis  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Oral mucosal erythema  1  2/66 (3.03%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Oral pain  1  2/66 (3.03%)  4/66 (6.06%)  0/7 (0.00%)  7/67 (10.45%)  2/25 (8.00%) 
Stomatitis  1  10/66 (15.15%)  12/66 (18.18%)  3/7 (42.86%)  14/67 (20.90%)  16/25 (64.00%) 
Vomiting  1  16/66 (24.24%)  23/66 (34.85%)  3/7 (42.86%)  14/67 (20.90%)  5/25 (20.00%) 
General disorders           
Asthenia  1  4/66 (6.06%)  7/66 (10.61%)  2/7 (28.57%)  3/67 (4.48%)  1/25 (4.00%) 
Chest discomfort  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  2/25 (8.00%) 
Chills  1  5/66 (7.58%)  0/66 (0.00%)  4/7 (57.14%)  1/67 (1.49%)  1/25 (4.00%) 
Fatigue  1  24/66 (36.36%)  27/66 (40.91%)  3/7 (42.86%)  20/67 (29.85%)  5/25 (20.00%) 
Influenza like illness  1  1/66 (1.52%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  4/25 (16.00%) 
Malaise  1  0/66 (0.00%)  2/66 (3.03%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Mucosal inflammation  1  19/66 (28.79%)  21/66 (31.82%)  2/7 (28.57%)  12/67 (17.91%)  5/25 (20.00%) 
Oedema peripheral  1  6/66 (9.09%)  4/66 (6.06%)  1/7 (14.29%)  4/67 (5.97%)  3/25 (12.00%) 
Pain  1  5/66 (7.58%)  7/66 (10.61%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Pyrexia  1  3/66 (4.55%)  4/66 (6.06%)  1/7 (14.29%)  0/67 (0.00%)  4/25 (16.00%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Immune system disorders           
Immunosuppression  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Infections and infestations           
Bronchitis  1  2/66 (3.03%)  2/66 (3.03%)  0/7 (0.00%)  1/67 (1.49%)  2/25 (8.00%) 
Cellulitis  1  1/66 (1.52%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  2/25 (8.00%) 
Cystitis  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  1/25 (4.00%) 
Folliculitis  1  0/66 (0.00%)  1/66 (1.52%)  2/7 (28.57%)  0/67 (0.00%)  0/25 (0.00%) 
Fungal skin infection  1  1/66 (1.52%)  2/66 (3.03%)  0/7 (0.00%)  4/67 (5.97%)  0/25 (0.00%) 
Herpes zoster  1  1/66 (1.52%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  2/25 (8.00%) 
Mucosal infection  1  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Otitis externa  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Paronychia  1  12/66 (18.18%)  10/66 (15.15%)  3/7 (42.86%)  9/67 (13.43%)  16/25 (64.00%) 
Pneumonia  1  2/66 (3.03%)  2/66 (3.03%)  1/7 (14.29%)  2/67 (2.99%)  2/25 (8.00%) 
Rash pustular  1  4/66 (6.06%)  2/66 (3.03%)  0/7 (0.00%)  7/67 (10.45%)  2/25 (8.00%) 
Upper respiratory tract infection  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  3/67 (4.48%)  7/25 (28.00%) 
Urinary tract infection  1  8/66 (12.12%)  7/66 (10.61%)  1/7 (14.29%)  2/67 (2.99%)  3/25 (12.00%) 
Vulvovaginal mycotic infection  1  1/66 (1.52%)  2/66 (3.03%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Injury, poisoning and procedural complications           
Contusion  1  3/66 (4.55%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  2/25 (8.00%) 
Fall  1  5/66 (7.58%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  1/25 (4.00%) 
Limb injury  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Rib fracture  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  2/66 (3.03%)  0/66 (0.00%)  2/7 (28.57%)  2/67 (2.99%)  3/25 (12.00%) 
Aspartate aminotransferase increased  1  6/66 (9.09%)  1/66 (1.52%)  1/7 (14.29%)  3/67 (4.48%)  3/25 (12.00%) 
Blood alkaline phosphatase increased  1  3/66 (4.55%)  1/66 (1.52%)  0/7 (0.00%)  4/67 (5.97%)  1/25 (4.00%) 
Blood creatinine increased  1  8/66 (12.12%)  5/66 (7.58%)  1/7 (14.29%)  3/67 (4.48%)  1/25 (4.00%) 
Transaminases increased  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Weight decreased  1  15/66 (22.73%)  15/66 (22.73%)  2/7 (28.57%)  8/67 (11.94%)  7/25 (28.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  24/66 (36.36%)  22/66 (33.33%)  3/7 (42.86%)  25/67 (37.31%)  14/25 (56.00%) 
Dehydration  1  15/66 (22.73%)  15/66 (22.73%)  1/7 (14.29%)  9/67 (13.43%)  1/25 (4.00%) 
Hyperkalaemia  1  0/66 (0.00%)  1/66 (1.52%)  1/7 (14.29%)  2/67 (2.99%)  0/25 (0.00%) 
Hypermagnesaemia  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Hypoalbuminaemia  1  8/66 (12.12%)  1/66 (1.52%)  1/7 (14.29%)  2/67 (2.99%)  2/25 (8.00%) 
Hypokalaemia  1  9/66 (13.64%)  10/66 (15.15%)  0/7 (0.00%)  10/67 (14.93%)  2/25 (8.00%) 
Hypomagnesaemia  1  7/66 (10.61%)  14/66 (21.21%)  1/7 (14.29%)  8/67 (11.94%)  1/25 (4.00%) 
Hyponatraemia  1  4/66 (6.06%)  7/66 (10.61%)  2/7 (28.57%)  2/67 (2.99%)  2/25 (8.00%) 
Hypophosphataemia  1  2/66 (3.03%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  2/66 (3.03%)  7/66 (10.61%)  0/7 (0.00%)  4/67 (5.97%)  0/25 (0.00%) 
Back pain  1  3/66 (4.55%)  5/66 (7.58%)  1/7 (14.29%)  6/67 (8.96%)  3/25 (12.00%) 
Flank pain  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  0/67 (0.00%)  2/25 (8.00%) 
Muscle spasms  1  4/66 (6.06%)  6/66 (9.09%)  1/7 (14.29%)  1/67 (1.49%)  2/25 (8.00%) 
Musculoskeletal chest pain  1  3/66 (4.55%)  4/66 (6.06%)  0/7 (0.00%)  5/67 (7.46%)  1/25 (4.00%) 
Musculoskeletal pain  1  2/66 (3.03%)  1/66 (1.52%)  1/7 (14.29%)  6/67 (8.96%)  6/25 (24.00%) 
Myalgia  1  1/66 (1.52%)  2/66 (3.03%)  0/7 (0.00%)  0/67 (0.00%)  5/25 (20.00%) 
Pain in extremity  1  3/66 (4.55%)  4/66 (6.06%)  0/7 (0.00%)  1/67 (1.49%)  2/25 (8.00%) 
Nervous system disorders           
Dizziness  1  6/66 (9.09%)  2/66 (3.03%)  1/7 (14.29%)  2/67 (2.99%)  4/25 (16.00%) 
Dysgeusia  1  5/66 (7.58%)  7/66 (10.61%)  0/7 (0.00%)  7/67 (10.45%)  2/25 (8.00%) 
Headache  1  5/66 (7.58%)  5/66 (7.58%)  1/7 (14.29%)  1/67 (1.49%)  5/25 (20.00%) 
Hypoaesthesia  1  1/66 (1.52%)  2/66 (3.03%)  0/7 (0.00%)  0/67 (0.00%)  4/25 (16.00%) 
Psychiatric disorders           
Anxiety  1  4/66 (6.06%)  3/66 (4.55%)  1/7 (14.29%)  3/67 (4.48%)  1/25 (4.00%) 
Confusional state  1  2/66 (3.03%)  1/66 (1.52%)  0/7 (0.00%)  2/67 (2.99%)  2/25 (8.00%) 
Insomnia  1  4/66 (6.06%)  9/66 (13.64%)  1/7 (14.29%)  3/67 (4.48%)  4/25 (16.00%) 
Renal and urinary disorders           
Dysuria  1  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Haematuria  1  3/66 (4.55%)  1/66 (1.52%)  0/7 (0.00%)  5/67 (7.46%)  3/25 (12.00%) 
Pollakiuria  1  1/66 (1.52%)  1/66 (1.52%)  1/7 (14.29%)  3/67 (4.48%)  1/25 (4.00%) 
Proteinuria  1  1/66 (1.52%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  1/25 (4.00%) 
Reproductive system and breast disorders           
Benign prostatic hyperplasia  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  1/67 (1.49%)  3/25 (12.00%) 
Genital rash  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  8/66 (12.12%)  6/66 (9.09%)  3/7 (42.86%)  7/67 (10.45%)  8/25 (32.00%) 
Dysphonia  1  2/66 (3.03%)  0/66 (0.00%)  0/7 (0.00%)  3/67 (4.48%)  2/25 (8.00%) 
Dyspnoea  1  8/66 (12.12%)  9/66 (13.64%)  2/7 (28.57%)  8/67 (11.94%)  4/25 (16.00%) 
Epistaxis  1  10/66 (15.15%)  4/66 (6.06%)  1/7 (14.29%)  6/67 (8.96%)  7/25 (28.00%) 
Haemoptysis  1  4/66 (6.06%)  6/66 (9.09%)  0/7 (0.00%)  3/67 (4.48%)  2/25 (8.00%) 
Hiccups  1  0/66 (0.00%)  1/66 (1.52%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Nasal congestion  1  1/66 (1.52%)  1/66 (1.52%)  0/7 (0.00%)  1/67 (1.49%)  5/25 (20.00%) 
Oropharyngeal pain  1  5/66 (7.58%)  2/66 (3.03%)  1/7 (14.29%)  2/67 (2.99%)  2/25 (8.00%) 
Pleural effusion  1  4/66 (6.06%)  2/66 (3.03%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Productive cough  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  2/67 (2.99%)  7/25 (28.00%) 
Rhinitis allergic  1  1/66 (1.52%)  3/66 (4.55%)  0/7 (0.00%)  2/67 (2.99%)  7/25 (28.00%) 
Rhinorrhoea  1  7/66 (10.61%)  2/66 (3.03%)  2/7 (28.57%)  3/67 (4.48%)  4/25 (16.00%) 
Sputum increased  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  2/66 (3.03%)  4/66 (6.06%)  0/7 (0.00%)  3/67 (4.48%)  4/25 (16.00%) 
Dermatitis acneiform  1  16/66 (24.24%)  12/66 (18.18%)  2/7 (28.57%)  20/67 (29.85%)  18/25 (72.00%) 
Dry skin  1  27/66 (40.91%)  19/66 (28.79%)  2/7 (28.57%)  15/67 (22.39%)  14/25 (56.00%) 
Erythema  1  12/66 (18.18%)  10/66 (15.15%)  1/7 (14.29%)  7/67 (10.45%)  3/25 (12.00%) 
Hypertrichosis  1  0/66 (0.00%)  0/66 (0.00%)  2/7 (28.57%)  1/67 (1.49%)  0/25 (0.00%) 
Ingrowing nail  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  1/67 (1.49%)  0/25 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  7/66 (10.61%)  5/66 (7.58%)  0/7 (0.00%)  4/67 (5.97%)  6/25 (24.00%) 
Papule  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  2/67 (2.99%)  1/25 (4.00%) 
Pruritus  1  7/66 (10.61%)  13/66 (19.70%)  3/7 (42.86%)  13/67 (19.40%)  17/25 (68.00%) 
Pruritus generalised  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  2/67 (2.99%)  0/25 (0.00%) 
Rash  1  28/66 (42.42%)  29/66 (43.94%)  5/7 (71.43%)  25/67 (37.31%)  5/25 (20.00%) 
Rash erythematous  1  1/66 (1.52%)  1/66 (1.52%)  1/7 (14.29%)  1/67 (1.49%)  1/25 (4.00%) 
Rash maculo-papular  1  3/66 (4.55%)  8/66 (12.12%)  1/7 (14.29%)  8/67 (11.94%)  7/25 (28.00%) 
Rash papular  1  2/66 (3.03%)  4/66 (6.06%)  0/7 (0.00%)  0/67 (0.00%)  2/25 (8.00%) 
Skin exfoliation  1  5/66 (7.58%)  8/66 (12.12%)  0/7 (0.00%)  5/67 (7.46%)  0/25 (0.00%) 
Skin fissures  1  2/66 (3.03%)  6/66 (9.09%)  1/7 (14.29%)  9/67 (13.43%)  5/25 (20.00%) 
Skin lesion  1  4/66 (6.06%)  0/66 (0.00%)  0/7 (0.00%)  2/67 (2.99%)  0/25 (0.00%) 
Trichorrhexis  1  0/66 (0.00%)  0/66 (0.00%)  2/7 (28.57%)  0/67 (0.00%)  0/25 (0.00%) 
Vascular disorders           
Hyperaemia  1  0/66 (0.00%)  0/66 (0.00%)  1/7 (14.29%)  0/67 (0.00%)  0/25 (0.00%) 
Hypertension  1  0/66 (0.00%)  0/66 (0.00%)  0/7 (0.00%)  0/67 (0.00%)  2/25 (8.00%) 
Hypotension  1  9/66 (13.64%)  3/66 (4.55%)  1/7 (14.29%)  4/67 (5.97%)  0/25 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01465802    
Other Study ID Numbers: A7471042
First Submitted: October 20, 2011
First Posted: November 6, 2011
Results First Submitted: April 15, 2016
Results First Posted: August 17, 2016
Last Update Posted: January 9, 2019