Non Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
non-small cell lung cancer, advanced, previously treated
Brief summary
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).
Interventions
DRUGDacomitinib
Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
DRUGDoxycycline
Doxycycline or Doxycycline placebo BID for 4 weeks
DRUGProbiotic
VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)
DRUGAlclometasone cream
Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced Non-Small Cell Lung Cancer (NSCLC). * For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated. * For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed\>12 months prior to enrollment. * All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll. * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 * Estimated creatinine clearance ≥15 mL/min.
Exclusion criteria
* Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts). * Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts). * Patients with known diffuse interstitial lung disease (all cohorts). * Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | 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). | Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax. |
| Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II | First 8 Weeks of Treatment | 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. |
| 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 | Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up | 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. |
| Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II | First 8 Weeks of Treatment | 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. |
| Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II | First 8 Weeks of Treatment | 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. |
| Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up | 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. |
| 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 | 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). | 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 |
| Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | 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). | Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter |
| 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 | First 8 Weeks of Treatment | 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. |
| 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 | First 8 Weeks of Treatment | 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. |
| 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 | First 8 Weeks of Treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose | 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. |
| Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose | Cmax was obtained from direct inspection of the data. |
| Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose | Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax. |
| Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I | Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose | CL/F was calculated as dose/AUCtau. |
| Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10. | 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. |
| Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10. | 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. |
| 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 | 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) | 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). |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) 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). | 66 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) 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). | 66 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) 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). | 7 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) 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). | 67 |
| Cohort III (Dacomitinib 45 mg) 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. | 25 |
| Total | 231 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 15 | 12 | 0 | 10 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Reason not specified | 9 | 4 | 0 | 10 | 2 |
| Overall Study | Study terminated by sponsor | 1 | 0 | 0 | 1 | 7 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 0 | 8 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.0 Years STANDARD_DEVIATION 10.38 | 64.4 Years STANDARD_DEVIATION 10.55 | 61.3 Years STANDARD_DEVIATION 7.67 | 66.0 Years STANDARD_DEVIATION 9.63 | 64.2 Years STANDARD_DEVIATION 14.29 | 64.9 Years STANDARD_DEVIATION 10.59 |
| Sex: Female, Male Female | 38 Participants | 27 Participants | 2 Participants | 24 Participants | 18 Participants | 109 Participants |
| Sex: Female, Male Male | 28 Participants | 39 Participants | 5 Participants | 43 Participants | 7 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 65 / 66 | 66 / 66 | 7 / 7 | 64 / 67 | 25 / 25 |
| serious Total, serious adverse events | 25 / 66 | 27 / 66 | 3 / 7 | 22 / 67 | 6 / 25 |
Outcome results
Primary
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
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | PF-05199265 AUC0-120 | 742.32 ng*hr/mL | Geometric Coefficient of Variation 129 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Dacomitinib AUC0-24 | 1712.88 ng*hr/mL | Geometric Coefficient of Variation 35 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Dacomitinib AUC0-120 | 5743.60 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | PF-05199265 AUC0-24 | 184.62 ng*hr/mL | Geometric Coefficient of Variation 139 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 1 Day 15 (n=37) | 3.2 Score on a scale | Standard Deviation 2.94 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 2 Day 8 (n=34) | 2.2 Score on a scale | Standard Deviation 3 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 2 Day 15 (n=36) | 2.1 Score on a scale | Standard Deviation 3.13 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Follow-up (n=22) | -0.1 Score on a scale | Standard Deviation 0.94 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 1 Day 8 (n=37) | 1.2 Score on a scale | Standard Deviation 1.89 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 5 Day 1 (n=10) | 2.7 Score on a scale | Standard Deviation 2.31 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 1 Day 8 (n=37) | 0.8 Score on a scale | Standard Deviation 2.05 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 1 Day 15 (n=37) | 2.5 Score on a scale | Standard Deviation 3.12 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 1 Day 22 (n=37) | 2.6 Score on a scale | Standard Deviation 2.97 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 2 Day 1 (n=37) | 2.5 Score on a scale | Standard Deviation 2.43 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 2 Day 8 (n=35) | 1.9 Score on a scale | Standard Deviation 2.3 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 2 Day 15 (n=36) | 1.7 Score on a scale | Standard Deviation 1.97 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 2 Day 22 (n=27) | 1.6 Score on a scale | Standard Deviation 1.85 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 3 Day 1 (n=19) | 2.1 Score on a scale | Standard Deviation 2.09 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 4 Day 1 (n=13) | 1.7 Score on a scale | Standard Deviation 2.14 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 5 Day 1 (n=10) | 1.0 Score on a scale | Standard Deviation 1.29 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Cycle 6 Day 1 (n=8) | 0.3 Score on a scale | Standard Deviation 0.88 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: EoT (n=30) | 1.4 Score on a scale | Standard Deviation 2.34 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Categories: Follow-up (n=22) | 0.3 Score on a scale | Standard Deviation 2.48 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 1 Day 8 (n=37) | 1.0 Score on a scale | Standard Deviation 2 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 1 Day 15 (n=37) | 2.5 Score on a scale | Standard Deviation 3 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 1 Day 22 (n=37) | 2.2 Score on a scale | Standard Deviation 2.51 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 2 Day 1 (n=37) | 2.2 Score on a scale | Standard Deviation 2.28 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 2 Day 8 (n=35) | 1.7 Score on a scale | Standard Deviation 1.97 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 2 Day 15 (n=36) | 1.6 Score on a scale | Standard Deviation 1.83 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 2 Day 22 (n=27) | 1.9 Score on a scale | Standard Deviation 2.45 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 3 Day 1 (n=19) | 2.2 Score on a scale | Standard Deviation 2.81 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 4 Day 1 (n=13) | 1.6 Score on a scale | Standard Deviation 2.81 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 5 Day 1 (n=10) | 1.0 Score on a scale | Standard Deviation 1.76 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Cycle 6 Day 1 (n=8) | 0.1 Score on a scale | Standard Deviation 0.35 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: EoT (n=30) | 1.3 Score on a scale | Standard Deviation 1.78 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | M/T Soreness Scale: Follow-up (n=22) | 0.5 Score on a scale | Standard Deviation 1.68 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 1 Day 8 (n=37) | 2.1 Score on a scale | Standard Deviation 2.67 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 1 Day 22 (n=36) | 3.9 Score on a scale | Standard Deviation 3.19 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 2 Day 1 (n=37) | 3.0 Score on a scale | Standard Deviation 2.83 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 2 Day 22 (n=27) | 2.7 Score on a scale | Standard Deviation 3.1 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 3 Day 1 (n=19) | 2.8 Score on a scale | Standard Deviation 2.75 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 4 Day 1 (n=13) | 2.3 Score on a scale | Standard Deviation 3.14 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 5 Day 1 (n=10) | 3.8 Score on a scale | Standard Deviation 3.39 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: Cycle 6 Day 1 (n=8) | 1.9 Score on a scale | Standard Deviation 2.22 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Categories: EoT (n=30) | 1.9 Score on a scale | Standard Deviation 3.39 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 1 Day 15 (n=37) | 2.4 Score on a scale | Standard Deviation 2.55 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 1 Day 22 (n=36) | 3.0 Score on a scale | Standard Deviation 2.96 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 2 Day 1 (n=37) | 2.5 Score on a scale | Standard Deviation 2.61 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 2 Day 8 (n=34) | 2.0 Score on a scale | Standard Deviation 2.75 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 2 Day 15 (n=35) | 1.7 Score on a scale | Standard Deviation 2.71 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 2 Day 22 (n=27) | 2.0 Score on a scale | Standard Deviation 2.16 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 3 Day 1 (n=19) | 2.4 Score on a scale | Standard Deviation 2.34 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 4 Day 1 (n=13) | 1.8 Score on a scale | Standard Deviation 2.13 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Cycle 6 Day 1 (n=8) | 1.5 Score on a scale | Standard Deviation 1.93 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: EoT (n=30) | 1.6 Score on a scale | Standard Deviation 2.87 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Diarrhea Scale: Follow-up (n=22) | -0.1 Score on a scale | Standard Deviation 0.71 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 2 Day 8 (n=42, 39, 4) | 7.0 Score on a scale | Standard Deviation 18.51 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 1 Day 8 (n=41, 42, 4) | 3.7 Score on a scale | Standard Deviation 21.08 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 2 Day 8 (n=42, 39, 4) | 15.1 Score on a scale | Standard Deviation 25.55 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 2 Day 1 (n=41, 42, 4) | 8.5 Score on a scale | Standard Deviation 21.53 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 1 Day 15 (n=41, 42, 3) | 20.7 Score on a scale | Standard Deviation 28.51 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 1 Day 8 (n=41, 42, 4) | 2.3 Score on a scale | Standard Deviation 10.12 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 1 Day 22 (n=42, 40, 4) | 11.7 Score on a scale | Standard Deviation 21.68 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 1 Day 22 (n=42, 40, 4) | 17.7 Score on a scale | Standard Deviation 27.67 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 2 Day 22 (n=35, 39, 4) | 12.7 Score on a scale | Standard Deviation 21.24 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 1 Day 15 (n=41, 42, 3) | 11.1 Score on a scale | Standard Deviation 21.41 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 2 Day 1 (n=41, 42, 4) | 15.6 Score on a scale | Standard Deviation 25.15 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 2 Day 1 (n=41, 42, 4) | 13.1 Score on a scale | Standard Deviation 20.74 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 1 Day 8 (n=41, 42, 4) | 3.1 Score on a scale | Standard Deviation 17.6 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 1 Day 15 (n=41, 42, 3) | 21.4 Score on a scale | Standard Deviation 30.98 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: EoT (n=7, 3, 0) | 9.9 Score on a scale | Standard Deviation 21.27 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 2 Day 15 (n=37, 40, 4) | 13.0 Score on a scale | Standard Deviation 22.7 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 2 Day 15 (n=37, 40, 4) | 12.4 Score on a scale | Standard Deviation 20.39 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Emotion: Cycle 2 Day 22 (n=35, 39, 4) | 14.8 Score on a scale | Standard Deviation 25.91 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 1 Day 15 (n=41, 42, 3) | 17.9 Score on a scale | Standard Deviation 25.09 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 2 Day 22 (n=35, 39, 4) | 15.4 Score on a scale | Standard Deviation 22.34 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: EoT (n=7, 3, 0) | 8.6 Score on a scale | Standard Deviation 11.84 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 2 Day 1 (n=41, 42, 4) | 14.7 Score on a scale | Standard Deviation 23.74 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 1 Day 8 (n=41, 42, 4) | 3.2 Score on a scale | Standard Deviation 15.91 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 2 Day 22 (n=35, 39, 4) | 7.8 Score on a scale | Standard Deviation 22.32 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 2 Day 8 (n=42, 39, 4) | 17.8 Score on a scale | Standard Deviation 26.78 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 1 Day 22 (n=42, 40, 4) | 15.9 Score on a scale | Standard Deviation 23.39 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 1 Day 22 (n=42, 40, 4) | 18.0 Score on a scale | Standard Deviation 25.76 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: Cycle 2 Day 15 (n=37, 40, 4) | 16.6 Score on a scale | Standard Deviation 21.1 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: EoT (n=7, 3, 0) | 10.3 Score on a scale | Standard Deviation 18.79 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Functioning: Cycle 2 Day 15 (n=37, 40, 4) | 8.3 Score on a scale | Standard Deviation 22.2 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Symptoms: EoT (n=7, 3, 0) | 13.1 Score on a scale | Standard Deviation 32.85 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Total: Cycle 2 Day 8 (n=42, 39, 4) | 13.2 Score on a scale | Standard Deviation 21.17 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 2 Day 15 (n=37, 40, 4) | 2.7 Score on a scale | Standard Deviation 10.58 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 2 Day 22 (n=35, 39, 4) | 12.9 Score on a scale | Standard Deviation 22.72 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: EoT (n=7, 3, 0) | 14.4 Score on a scale | Standard Deviation 25.02 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 1 Day 22 (n=42, 40, 4) | 4.0 Score on a scale | Standard Deviation 13.33 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: EoT (n=7, 3, 0) | 18.4 Score on a scale | Standard Deviation 18.64 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 1 Day 8 (n=41, 42, 4) | -1.1 Score on a scale | Standard Deviation 10.91 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 1 Day 15 (n=41, 42, 3) | 5.0 Score on a scale | Standard Deviation 19.82 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 1 Day 22 (n=42, 40, 4) | 6.8 Score on a scale | Standard Deviation 20.45 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 2 Day 1 (n=41, 42, 4) | 6.3 Score on a scale | Standard Deviation 15.38 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 2 Day 8 (n=42, 39, 4) | 9.8 Score on a scale | Standard Deviation 20 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: Cycle 2 Day 15 (n=37, 40, 4) | 9.2 Score on a scale | Standard Deviation 19.54 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Symptoms: EoT (n=7, 3, 0) | 16.7 Score on a scale | Standard Deviation 19.09 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 1 Day 8 (n=41, 42, 4) | -2.5 Score on a scale | Standard Deviation 12.11 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 1 Day 15 (n=41, 42, 3) | 2.9 Score on a scale | Standard Deviation 17.14 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 1 Day 22 (n=42, 40, 4) | 3.7 Score on a scale | Standard Deviation 16.07 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 2 Day 1 (n=41, 42, 4) | 6.5 Score on a scale | Standard Deviation 15.25 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 2 Day 8 (n=42, 39, 4) | 6.3 Score on a scale | Standard Deviation 17.28 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 2 Day 15 (n=37, 40, 4) | 8.4 Score on a scale | Standard Deviation 20.2 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: Cycle 2 Day 22 (n=35, 39, 4) | 12.0 Score on a scale | Standard Deviation 23.73 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Emotion: EoT (n=7, 3, 0) | 22.2 Score on a scale | Standard Deviation 21.34 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 1 Day 8 (n=41, 42, 4) | -1.2 Score on a scale | Standard Deviation 5.5 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 1 Day 15 (n=41, 42, 3) | 0.6 Score on a scale | Standard Deviation 7.47 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 1 Day 22 (n=42, 40, 4) | 1.9 Score on a scale | Standard Deviation 8.86 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 2 Day 1 (n=41, 42, 4) | 2.1 Score on a scale | Standard Deviation 7.72 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 2 Day 8 (n=42, 39, 4) | 2.4 Score on a scale | Standard Deviation 9.52 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Functioning: Cycle 2 Day 22 (n=35, 39, 4) | 5.4 Score on a scale | Standard Deviation 13.78 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 1 Day 8 (n=41, 42, 4) | -1.7 Score on a scale | Standard Deviation 8.07 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 1 Day 15 (n=41, 42, 3) | 2.7 Score on a scale | Standard Deviation 13.08 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 2 Day 1 (n=41, 42, 4) | 5.1 Score on a scale | Standard Deviation 11.65 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 2 Day 8 (n=42, 39, 4) | 6.0 Score on a scale | Standard Deviation 13.49 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 2 Day 15 (n=37, 40, 4) | 6.8 Score on a scale | Standard Deviation 14.84 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Total: Cycle 2 Day 22 (n=35, 39, 4) | 10.1 Score on a scale | Standard Deviation 18.36 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 1 Day 8 (n=41, 42, 4) | 7.3 Score on a scale | Standard Deviation 14.68 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 2 Day 22 (n=35, 39, 4) | 12.9 Score on a scale | Standard Deviation 17.22 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 2 Day 1 (n=41, 42, 4) | 20.0 Score on a scale | Standard Deviation 21.26 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: EoT (n=7, 3, 0) | NA Score on a scale | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 2 Day 22 (n=35, 39, 4) | 14.2 Score on a scale | Standard Deviation 20.44 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 2 Day 8 (n=42, 39, 4) | 12.5 Score on a scale | Standard Deviation 20.79 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 2 Day 15 (n=37, 40, 4) | 19.8 Score on a scale | Standard Deviation 28.74 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 2 Day 8 (n=42, 39, 4) | 13.5 Score on a scale | Standard Deviation 19.36 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 2 Day 15 (n=37, 40, 4) | 13.3 Score on a scale | Standard Deviation 22.44 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 2 Day 1 (n=41, 42, 4) | 14.6 Score on a scale | Standard Deviation 18.48 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 2 Day 22 (n=35, 39, 4) | 14.6 Score on a scale | Standard Deviation 15.4 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 1 Day 22 (n=42, 40, 4) | 32.3 Score on a scale | Standard Deviation 25.54 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: EoT (n=7, 3, 0) | NA Score on a scale | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 2 Day 15 (n=37, 40, 4) | 18.4 Score on a scale | Standard Deviation 31.5 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 1 Day 8 (n=41, 42, 4) | 5.3 Score on a scale | Standard Deviation 9.36 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 1 Day 15 (n=41, 42, 3) | 30.6 Score on a scale | Standard Deviation 42.56 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 1 Day 22 (n=42, 40, 4) | 33.3 Score on a scale | Standard Deviation 31.39 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 1 Day 15 (n=41, 42, 3) | 28.4 Score on a scale | Standard Deviation 43.52 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 2 Day 15 (n=37, 40, 4) | 21.0 Score on a scale | Standard Deviation 40.49 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 1 Day 22 (n=42, 40, 4) | 35.0 Score on a scale | Standard Deviation 29.97 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 2 Day 22 (n=35, 39, 4) | 10.9 Score on a scale | Standard Deviation 17.39 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 2 Day 8 (n=42, 39, 4) | 21.6 Score on a scale | Standard Deviation 35.76 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Symptoms: Cycle 1 Day 8 (n=41, 42, 4) | 9.4 Score on a scale | Standard Deviation 14.18 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: EoT (n=7, 3, 0) | NA Score on a scale | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 2 Day 1 (n=41, 42, 4) | 23.4 Score on a scale | Standard Deviation 30.15 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: EoT (n=7, 3, 0) | NA Score on a scale | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 1 Day 8 (n=41, 42, 4) | -0.8 Score on a scale | Standard Deviation 1.67 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 1 Day 22 (n=42, 40, 4) | 37.7 Score on a scale | Standard Deviation 32.44 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 2 Day 1 (n=41, 42, 4) | 20.2 Score on a scale | Standard Deviation 21.75 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Functioning: Cycle 1 Day 15 (n=41, 42, 3) | 24.4 Score on a scale | Standard Deviation 42.34 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Emotion: Cycle 1 Day 15 (n=41, 42, 3) | 29.8 Score on a scale | Standard Deviation 45.03 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Total: Cycle 2 Day 8 (n=42, 39, 4) | 16.8 Score on a scale | Standard Deviation 24.54 |
Primary
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II
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
Population: PRO Skindex Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 1 Day 8 (n=40) | 0.1 Score on a scale | Standard Deviation 8.31 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 1 Day 22 (n=40) | 11.4 Score on a scale | Standard Deviation 18.17 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 2 Day 1 (n=40) | 11.4 Score on a scale | Standard Deviation 19.84 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 1 Day 15 (n=40) | 8.7 Score on a scale | Standard Deviation 23.57 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 3 Day 1 (n=21) | 11.0 Score on a scale | Standard Deviation 17.97 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: EoT (n=33) | 8.5 Score on a scale | Standard Deviation 23.38 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 2 Day 15 (n=38) | 7.0 Score on a scale | Standard Deviation 11.75 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 1 Day 8 (n=40) | 0.6 Score on a scale | Standard Deviation 6.83 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 2 Day 8 (n=38) | 9.9 Score on a scale | Standard Deviation 17.79 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 4 Day 1 (n=15) | 10.2 Score on a scale | Standard Deviation 12.49 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: EoT (n=33) | 8.7 Score on a scale | Standard Deviation 19.74 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 1 Day 15 (n=40) | 11.4 Score on a scale | Standard Deviation 21.25 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 2 Day 8 (n=38) | 13.5 Score on a scale | Standard Deviation 20.88 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 2 Day 15 (n=38) | 14.7 Score on a scale | Standard Deviation 17.83 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 2 Day 22 (n=30) | 13.6 Score on a scale | Standard Deviation 16.3 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 3 Day 1 (n=21) | 12.7 Score on a scale | Standard Deviation 19.56 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 4 Day 1 (n=15) | 11.9 Score on a scale | Standard Deviation 18.69 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 5 Day 1 (n=11) | 8.0 Score on a scale | Standard Deviation 22.24 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Cycle 6 Day 1 (n=8) | 12.0 Score on a scale | Standard Deviation 32.15 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: EoT (n=33) | 10.4 Score on a scale | Standard Deviation 21.33 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Symptoms: Follow-up (n=23) | 7.1 Score on a scale | Standard Deviation 23.15 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 1 Day 8 (n=40) | 1.0 Score on a scale | Standard Deviation 11.79 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 1 Day 22 (n=40) | 12.3 Score on a scale | Standard Deviation 24.63 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 2 Day 1 (n=40) | 10.2 Score on a scale | Standard Deviation 21.36 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 2 Day 8 (n=38) | 10.3 Score on a scale | Standard Deviation 21.77 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 2 Day 15 (n=37) | 13.5 Score on a scale | Standard Deviation 17.1 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 2 Day 22 (n= 30) | 12.6 Score on a scale | Standard Deviation 19.86 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 4 Day 1 (n=14) | 11.5 Score on a scale | Standard Deviation 14.65 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 5 Day 1 (n=11) | 7.8 Score on a scale | Standard Deviation 21.43 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Cycle 6 Day 1 (n=8) | 6.8 Score on a scale | Standard Deviation 22.67 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Emotion: Follow-up (n=23) | 7.1 Score on a scale | Standard Deviation 22.74 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 1 Day 8 (n=40) | 0.5 Score on a scale | Standard Deviation 3.58 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 1 Day 15 (n=40) | 4.3 Score on a scale | Standard Deviation 13.34 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 1 Day 22 (n=40) | 8.8 Score on a scale | Standard Deviation 17.55 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 2 Day 1 (n=40) | 7.3 Score on a scale | Standard Deviation 15.25 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 2 Day 8 (n=38) | 6.2 Score on a scale | Standard Deviation 15.33 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 2 Day 22 (n=30) | 7.2 Score on a scale | Standard Deviation 10.06 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 3 Day 1 (n=21) | 5.9 Score on a scale | Standard Deviation 8.09 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 4 Day 1 (n=15) | 6.9 Score on a scale | Standard Deviation 10.12 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 5 Day 1 (n=11) | 5.5 Score on a scale | Standard Deviation 12.93 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Cycle 6 Day 1 (n=8) | 7.1 Score on a scale | Standard Deviation 15.58 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: EoT (n=33) | 7.7 Score on a scale | Standard Deviation 17.35 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Functioning: Follow-up (n=23) | 5.4 Score on a scale | Standard Deviation 18.55 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 1 Day 15 (n=40) | 8.0 Score on a scale | Standard Deviation 18.73 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 1 Day 22 (n=40) | 11.0 Score on a scale | Standard Deviation 19.59 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 2 Day 1 (n=40) | 9.6 Score on a scale | Standard Deviation 17.38 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 2 Day 15 (n=38) | 11.8 Score on a scale | Standard Deviation 14.13 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 2 Day 22 (n=30) | 11.2 Score on a scale | Standard Deviation 14.14 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 3 Day 1 (n=21) | 9.8 Score on a scale | Standard Deviation 14.11 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 5 Day 1 (n=11) | 7.1 Score on a scale | Standard Deviation 18.6 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Cycle 6 Day 1 (n=8) | 8.2 Score on a scale | Standard Deviation 22.43 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II | Total: Follow-up (n=23) | 6.6 Score on a scale | Standard Deviation 20.52 |
Primary
Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | Dacomitinib Cmax | 79.68 ng/mL | Geometric Coefficient of Variation 36 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | PF-05199265 Cmax | 8.5176 ng/mL | Geometric Coefficient of Variation 137 |
Primary
Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
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).
Population: 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 | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | Dacomitinib Tmax | 5.850 hours (hr) | Full Range 53 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III | PF-05199265 Tmax | 5.980 hours (hr) | Full Range 126 |
Primary
Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
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
Population: Evaluable Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II | All Causality, All Grade | 83.1 Percentage of Participants |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II | All Causality, Grade ≥2 | 39.0 Percentage of Participants |
Primary
Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II
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
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II | 79.7 Percentage of Participants |
Primary
Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
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
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II | 35.6 Percentage of Participants |
Primary
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
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
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | 46.6 Percentage of Participants |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | 23.2 Percentage of Participants |
Primary
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
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | 79.3 Percentage of Participants |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | 75.0 Percentage of Participants |
Secondary
Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I | 29.94 Liters per hour | Geometric Coefficient of Variation 85 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I | 24.07 Liters per hour | Geometric Coefficient of Variation 37 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I | 34.24 Liters per hour | Geometric Coefficient of Variation 45 |
Secondary
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
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Dacomitinib AUC0-tau | 1801.96 ng*hr/mL | Geometric Coefficient of Variation 59 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | PF-05199265 AUC0-tau | 164.520 ng*hr/mL | Geometric Coefficient of Variation 89 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | PF-05199265 AUC0-tau | 112.306 ng*hr/mL | Geometric Coefficient of Variation 139 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Dacomitinib AUC0-tau | 1869.23 ng*hr/mL | Geometric Coefficient of Variation 37 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | PF-05199265 AUC0-tau | 366.933 ng*hr/mL | Geometric Coefficient of Variation 107 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Dacomitinib AUC0-tau | 1412.42 ng*hr/mL | Geometric Coefficient of Variation 63 |
Secondary
Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Cmax | 88.15 ng/mL | Geometric Coefficient of Variation 57 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Cmax | 7.7426 ng/mL | Geometric Coefficient of Variation 80 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Cmax | 89.79 ng/mL | Geometric Coefficient of Variation 36 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Cmax | 5.2901 ng/mL | Geometric Coefficient of Variation 141 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Cmax | 98.08 ng/mL | Geometric Coefficient of Variation 89 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Cmax | 8.8545 ng/mL | Geometric Coefficient of Variation 260 |
Secondary
Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 3.460 ng/mL | — |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 4.850 ng/mL | Geometric Coefficient of Variation 49 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 5.020 ng/mL | Geometric Coefficient of Variation 70 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 5.555 ng/mL | Geometric Coefficient of Variation 71 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 6.988 ng/mL | Geometric Coefficient of Variation 60 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 4.271 ng/mL | Geometric Coefficient of Variation 34 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 4.356 ng/mL | Geometric Coefficient of Variation 55 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 5.349 ng/mL | Geometric Coefficient of Variation 54 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 4.989 ng/mL | Geometric Coefficient of Variation 58 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 5.271 ng/mL | Geometric Coefficient of Variation 242 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 6.085 ng/mL | Geometric Coefficient of Variation 476 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 6.523 ng/mL | Geometric Coefficient of Variation 123 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 23.900 ng/mL | — |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 4.653 ng/mL | Geometric Coefficient of Variation 133 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 6.892 ng/mL | Geometric Coefficient of Variation 305 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 6.448 ng/mL | Geometric Coefficient of Variation 612 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 8.150 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 8.560 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 10.220 ng/mL | Geometric Coefficient of Variation 11 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 8.522 ng/mL | Geometric Coefficient of Variation 15 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 8.522 ng/mL | Geometric Coefficient of Variation 10 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 10.100 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 9.720 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 10.700 ng/mL | — |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 9.442 ng/mL | Geometric Coefficient of Variation 26 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 9.159 ng/mL | Geometric Coefficient of Variation 58 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 10.844 ng/mL | Geometric Coefficient of Variation 38 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 5.850 ng/mL | Geometric Coefficient of Variation 115 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 6.680 ng/mL | — |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 1.261 ng/mL | Geometric Coefficient of Variation 937 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 6.848 ng/mL | Geometric Coefficient of Variation 82 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 7.814 ng/mL | Geometric Coefficient of Variation 59 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 10.510 ng/mL | Geometric Coefficient of Variation 124 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 11.759 ng/mL | Geometric Coefficient of Variation 113 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 6.364 ng/mL | Geometric Coefficient of Variation 154 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 8.205 ng/mL | Geometric Coefficient of Variation 117 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 6.963 ng/mL | Geometric Coefficient of Variation 88 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 9.967 ng/mL | Geometric Coefficient of Variation 149 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 7.844 ng/mL | Geometric Coefficient of Variation 125 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 8.203 ng/mL | Geometric Coefficient of Variation 105 |
Secondary
Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 51.400 ng/mL | — |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 64.747 ng/mL | Geometric Coefficient of Variation 72 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 65.477 ng/mL | Geometric Coefficient of Variation 50 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 61.592 ng/mL | Geometric Coefficient of Variation 36 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 15.578 ng/mL | Geometric Coefficient of Variation 1208 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 59.086 ng/mL | Geometric Coefficient of Variation 47 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 89.970 ng/mL | Geometric Coefficient of Variation 38 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 61.430 ng/mL | Geometric Coefficient of Variation 90 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 68.012 ng/mL | Geometric Coefficient of Variation 39 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 72.856 ng/mL | Geometric Coefficient of Variation 47 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 58.988 ng/mL | Geometric Coefficient of Variation 31 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 65.063 ng/mL | Geometric Coefficient of Variation 55 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 54.041 ng/mL | Geometric Coefficient of Variation 48 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 58.928 ng/mL | Geometric Coefficient of Variation 31 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 40.900 ng/mL | — |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 67.109 ng/mL | Geometric Coefficient of Variation 29 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 65.466 ng/mL | Geometric Coefficient of Variation 49 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 56.212 ng/mL | Geometric Coefficient of Variation 46 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 69.649 ng/mL | Geometric Coefficient of Variation 63 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 46.000 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 59.900 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 47.00 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 46.000 ng/mL | — |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 58.800 ng/mL | — |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 71.695 ng/mL | Geometric Coefficient of Variation 26 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 64.115 ng/mL | Geometric Coefficient of Variation 30 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 71.116 ng/mL | Geometric Coefficient of Variation 49 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 42.600 ng/mL | — |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 66.082 ng/mL | Geometric Coefficient of Variation 33 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 64.296 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 9.201 ng/mL | Geometric Coefficient of Variation 3760 |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 66.338 ng/mL | Geometric Coefficient of Variation 58 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 6 Day 1 (n=2, 5, 1, 2, 10) | 52.603 ng/mL | Geometric Coefficient of Variation 52 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 3 Day 1 (n=13, 15, 3, 14, 15) | 55.780 ng/mL | Geometric Coefficient of Variation 40 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 7 Day 1 (n=2, 1, 1, 1, 8) | 55.685 ng/mL | Geometric Coefficient of Variation 21 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 10 Day 1 (n=1, 2, 1, 2, 4) | 55.362 ng/mL | Geometric Coefficient of Variation 32 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 9 Day 1 (n=2, 2, 1, 2, 6) | 44.865 ng/mL | Geometric Coefficient of Variation 50 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 5 Day 1 (n=3, 6, 2, 3, 12) | 53.116 ng/mL | Geometric Coefficient of Variation 44 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 8 Day 1 (n=2, 2, 1, 2, 8) | 51.559 ng/mL | Geometric Coefficient of Variation 24 |
| Cohort III (Dacomitinib 45 mg) | Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III | Cycle 4 Day 1 (n=8, 7, 2, 5, 13) | 55.644 ng/mL | Geometric Coefficient of Variation 42 |
Secondary
Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
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
Population: 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 | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Tmax | 4.000 hr | Full Range 67 |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Tmax | 4.050 hr | Full Range 82 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Tmax | 6.000 hr | Full Range 67 |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Tmax | 4.020 hr | Full Range 125 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | Dacomitinib Tmax | 6.580 hr | Full Range 108 |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I | PF-05199265 Tmax | 6.580 hr | Full Range 105 |
Secondary
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
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)
Population: As Treated Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Any Concomitant Drug | 69.7 Percentage of Participants |
| Cohort I: Arm A (Dacomitinib 45 mg + Doxycycline Placebo) | 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 | Any Non-Drug Treatment | 16.7 Percentage of Participants |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Any Concomitant Drug | 60.6 Percentage of Participants |
| Cohort I: Arm B (Dacomitinib 45 mg + Doxycycline 100 mg) | 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 | Any Non-Drug Treatment | 16.7 Percentage of Participants |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Any Concomitant Drug | 85.7 Percentage of Participants |
| Cohort I: Arm C (Dacomitinib 45mg+Alclometasone Diproprionate) | 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 | Any Non-Drug Treatment | 42.9 Percentage of Participants |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | 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 | Any Non-Drug Treatment | 20.9 Percentage of Participants |
| Cohort II (Dacomitinib 45mg + VSL#3 Probiotic + Alclometasone) | 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 | Any Concomitant Drug | 82.1 Percentage of Participants |
| Cohort III (Dacomitinib 45 mg) | 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 | Any Concomitant Drug | 88.0 Percentage of Participants |
| Cohort III (Dacomitinib 45 mg) | 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 | Any Non-Drug Treatment | 44.0 Percentage of Participants |