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Study to Investigate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years and Over With Moderate to Severe Atopic Dermatitis With the Option of Rescue Treatment in Flaring Subjects

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03627767
Collaborator
(none)
1,235
Enrollment
235
Locations
3
Arms
27.9
Actual Duration (Months)
5.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

B7451014 is a Phase 3 study to investigate PF-04965842 in patients aged 12 years and over with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. Subjects responding well to an initial open-label 12 week treatment of PF-04965842 (200 mg) taken orally once daily (QD) will be identified and randomized in a double-blind manner to receive 200 mg QD PF-04965842, 100 mg QD PF-04965842, or QD placebo. Efficacy and safety of 2 doses of PF-04965842 will be evaluated relative to placebo over 40 weeks. Subjects experiencing significant worsening of their symptoms, i.e., protocol-defined flare, enter 12 weeks rescue treatment and receive 200 mg PF-04965842 together with a marketed topical medicine. Eligible patients will have the option to enter a long-term extension study after completing the initial 12 week treatment, the 12 week rescue treatment, and the 40 week blinded treatment.

Condition or Disease Intervention/Treatment Phase
  • Drug: PF-04965842 100 mg
  • Drug: PF-04965842 200 mg
  • Drug: Placebo
 Phase 3

Detailed Description

Responder criteria for randomization at week 12 are defined as a) achieving an IGA of clear (0) or almost clear (1) (on a 5 point scale), b) a reduction from IGA baseline of 2 or more points, and c) reaching an EASI-75 response compared to baseline. Flare requiring rescue treatment is defined as a loss of at least 50% of the EASI response at Week 12 and an IGA score of 2 or higher.

Study Design

Study Type:
Interventional
Actual Enrollment :
1235 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A PHASE 3 RANDOMIZED WITHDRAWAL, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 IN SUBJECTS AGED 12 YEARS AND OVER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH THE OPTION OF RESCUE TREATMENT IN FLARING SUBJECTS
Actual Study Start Date :
Jun 11, 2018
Actual Primary Completion Date :
Sep 2, 2020
Actual Study Completion Date :
Oct 7, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-04965842 100 mg QD

Double-blind randomized treatment following open label run-in period.

Drug: PF-04965842 100 mg
PF-04965842 100 mg, administered as two tablets to be taken orally once daily for 40 weeks
Other Names:
  • Abrocitinib

    		•
    Experimental: PF-04965842 200 mg QD

    Double-blind randomized treatment following open label run-in period.

    Drug: PF-04965842 200 mg
    PF-04965842 200 mg, administered as two tablets to be taken orally once daily for 40 weeks
    Other Names:
  • Abrocitinib

    		•
    Placebo Comparator: Placebo QD

    Double-blind randomized treatment following open label run-in period.

    Drug: Placebo
    Placebo, administered as two tablets to be taken orally once daily for 40 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Loss of Response: Double-blind (DB) Period [From Day 1 of up to Week 40 of double blind period]

      Percentage of participants with loss of response requiring rescue treatment during double blind period was determined. Loss of response denoted as flare and was define as a loss of at least 50% of EASI total score at Week 12 and with an IGA score of 2 or higher. EASI quantifies severity of participant's atopic dermatitis (AD) based on both severity of lesion clinical signs and % of body surface area (BSA) affected. EASI is a composite scoring by AD clinical evaluator of degree of erythema, induration/papulation, excoriation, and lichenification for each of 4 body regions. EASI total score range from 0.0 to 72.0, with higher scores representing greater severity of AD. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores = more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate and 4 = severe.

    2. Time to Loss of Response: Double-blind Period [From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window was extended +/- 45 Days due to COVID 19)]

      Time (in days) to loss of response based on achieving IGA >=2 was measured from date of first dose of randomized treatment until last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) and based on EASI, loss of at least 50% of EASI response at Week 12 and IGA score of 2 or higher. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores=more severity), reflecting global consideration of erythema, induration and scaling with scores 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. EASI composite score evaluates degree of erythema, induration/papulation, excoriation, and lichenification.

    Secondary Outcome Measures

    1. Time to First Loss of Response Based on Investigator's Global Assessment (IGA) Score of 2 or Higher: Double-blind Period [From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window +/- 7 Days)]

      Time (in days) to loss of response based on achieving IGA >=2 (for the first time) as measured from date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue). IGA assesses severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep, dark red lesions.

    2. Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Weeks 12, 16, 28, 40, and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      IGA assessed severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep dark red lesions.

    3. Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=50% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema [E], induration/papulation [I], excoriation [Ex] and lichenification [L]) was scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin] and lower limbs [l] [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); where A = area score. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.

    4. Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.

    5. Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=90% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.

    6. Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=100% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.

    7. Percentage of Participants With Greater Than or Equal 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated worse disease status.

    8. Percent Change From Baseline in Body Surface Area (BSA) at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      4 body regions evaluated: head and neck, upper limbs, trunk (including axillae, groin/genitals), lower limbs (including buttocks) excluding scalp, palms, soles. BSA calculated by handprint method. Number (No) of handprints (size of participant's hand with fingers in closed position) fitting in affected area of a body region was estimated. Maximum No of handprints were 10, 20, 30, 40 for head and neck, upper limbs, trunk, and lower limbs respectively. Surface area (SA) of body region equivalent to 1 handprint: 1 handprint=10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. %Change BSA for a body region was calculated as=total No of handprints in a body region* %SA equivalent to 1 handprint. %BSA for an individual: arithmetic mean of %BSA of all 4 body regions, ranged from 0-100%, higher values=greater AD severity.

    9. Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3); severity scores added to give B (0-18). C: pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    10. Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch and Sleep Loss at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region-head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    11. Percentage of Participants With >=50% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    12. Percentage of Participants With >=75% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    13. Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      IGA assessed severity of AD on a 5-point scale (0-4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0=clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep, dark red lesions.

    14. Percent Change From Rescue Baseline in Total Eczema Area and Severity Index (EASI) Score at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.

    15. Percentage of Participants Achieving Greater Than or Equal to 4 Points Improvement From Rescue Baseline in Peak Pruritus Numeric Rating Scale (PP-NRS) at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity.

    16. Percent Change From Rescue Baseline in Percent Body Surface Area (BSA) at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin/genitals) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Overall % BSA for an individual % BSA of all 4 body regions, ranged from 0 to 100%, with higher values representing greater severity of AD.

    17. Percent Change From Rescue Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) Score of Itch and Sleep Loss at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    18. Percentage of Participants With 50% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    19. Percentage of Participants With 75% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period [Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12]

      SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.

    20. Percentage of Participants Achieving Patient Global Assessment (PtGA) Response of 'Clear (0)' or 'Almost Clear (1)' and Greater Than or Equal to 2 Points Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      Participant responded to the following question: "Overall, how would you describe your Atopic Dermatitis right now?" on a 5-point scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity.

    21. Change From Baseline in Dermatology Life Quality Index (DLQI) Score for Adults at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      DLQI was a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.

    22. Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score for Adolescents at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      CDLQI is a 10-item questionnaire that measures the impact of skin disease on adolescents (aged 12-17 years) quality of life over the last week. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all , 1 = only a little, 2 = quite a lot, 3 = very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give CDLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of children.

    23. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.

    24. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Depression Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms.

    25. Change From Baseline in Patient Oriented Eczema Measure (POEM) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      POEM was a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item scored as following: no days = 0, 1-2 days = 1, 3-4 days = 2, 5-6 days = 3 and, every day = 4. The total POEM score ranges from 0 to 28, where higher score indicated greater severity.

    26. Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period [Baseline, Weeks 12, 16, 28, 40 and 52]

      PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [darker or lighter], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participants had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 12 years of age or older with a minimum body weight of 40 kg

    • Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA10%, IGA 3, EASI 16, Pruritus NRS 4)

    • Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control

    Exclusion Criteria:

    • Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study

    • Prior treatment with JAK inhibitors

    • Other active nonAD inflammatory skin diseases or conditions affecting skin

    • Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator

    • Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Total Skin and Beauty Dermatology Center, PC Birmingham Alabama United States 35205
    2 University of Alabama at Birmingham, Dermatology at the Whitaker Clinic Birmingham Alabama United States 35233
    3 Clinical Research Center of Alabama, LLC Birmingham Alabama United States 35244
    4 Tien Q Nguyen MD Inc dba First OC Dermatology Fountain Valley California United States 92708
    5 Center for Dermatology Clinical Research, Inc. Fremont California United States 94538
    6 Beach Allergy and Asthma Specialty Group, A Medical Corporation Long Beach California United States 90808
    7 Dermatology Specialists, Inc. Oceanside California United States 92056
    8 University of California San Diego San Diego California United States 92122
    9 San Luis Dermatology and Laser Clinic San Luis Obispo California United States 93405
    10 Southern California Dermatology, Inc. Santa Ana California United States 92701
    11 Mosaic Dermatology Santa Monica California United States 90403
    12 Bay Pines VAHCS Bay Pines Florida United States 33744
    13 Skin Care Research, LLC Boca Raton Florida United States 33486
    14 Skin Research Institute Coral Gables Florida United States 33146
    15 Baumann Cosmetic and Research Institute Miami Florida United States 33137
    16 Park Avenue Dermatology Orange Park Florida United States 32073
    17 USF Asthma, Allergy & Immunology Clinical Research Unit Tampa Florida United States 33613
    18 Emory University Atlanta Georgia United States 30322
    19 Dermatologic Surgery Specialists, PC Macon Georgia United States 31217
    20 Midwest Allergy Sinus Asthma, SC Normal Illinois United States 61761
    21 NorthShore University HealthSystem Dermatology Clinical Trials Unit Skokie Illinois United States 60077
    22 Dawes Fretzin Clinical Research Group, LLC Indianapolis Indiana United States 46250
    23 Ds Research New Albany Indiana United States 47150
    24 The Indiana Clinical Trials Center Plainfield Indiana United States 46168
    25 Kansas City Dermatology, P.A. Overland Park Kansas United States 66215
    26 DXP Imaging Louisville Kentucky United States 40216
    27 Skin Sciences PLLC Louisville Kentucky United States 40217
    28 Qualmedica Research, LLC Owensboro Kentucky United States 42301
    29 Owensboro Dermatology Associates Owensboro Kentucky United States 42303
    30 Meridian Clinical Research, LLC Baton Rouge Louisiana United States 70808
    31 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    32 Tufts Medical Center Boston Massachusetts United States 02111
    33 Mayo Clinic Rochester Minnesota United States 55905
    34 MediSearch Clinical Trials Saint Joseph Missouri United States 64506
    35 Saint Louis University Dermatology Saint Louis Missouri United States 63104
    36 Forest Hills Dermatology Group Kew Gardens New York United States 11374
    37 Juva Skin and Laser Center New York New York United States 10022
    38 UR Dermatology at College Town Rochester New York United States 14620
    39 M3 - Wake Research, Inc. Raleigh North Carolina United States 27612
    40 Bexley Dermatology Research Bexley Ohio United States 43209
    41 Lynn Health Science Institute Oklahoma City Oklahoma United States 73112
    42 Newton Clinical Research Oklahoma City Oklahoma United States 73120
    43 Oregon Medical Research Center Portland Oregon United States 97223
    44 Paddington Testing Co, Inc. Philadelphia Pennsylvania United States 19103
    45 Health Concepts Rapid City South Dakota United States 57702
    46 Dermatology Treatment & Research Center, PA Dallas Texas United States 75230
    47 Innovate Research, LLC Fort Worth Texas United States 76244
    48 The University of Texas Health Science Center Houston Houston Texas United States 77030
    49 Ventavia Research Group Hurst Hurst Texas United States 76054
    50 Virginia Clinical Research, Inc Norfolk Virginia United States 23502
    51 Dermatology Associates of Seattle Seattle Washington United States 98101
    52 Dermatology Specialists of Spokane Spokane Washington United States 99202
    53 Framingham Centro Medico La Plata Buenos Aires Argentina B1902COS
    54 Hospital Universitario Austral Pilar Buenos Aires Argentina B1629ODT
    55 Servicio de Investigacion de Patolog-ias Alergicas del Instituto ABC Rosario Santa FE Argentina 2000
    56 CINME Centro de Investigaciones Metabolicas C.a.b.a. Argentina C1027AAP
    57 Buenos Aires Skin C.a.b.a. Argentina C1055AAO
    58 Psoriahue Medicina Interdisciplinaria C.a.b.a Argentina C1425DKG
    59 University Hospital Brussels Brussels Belgium 1090
    60 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
    61 University Hospital Antwerp Edegem Belgium 2650
    62 CETI - Centro de Estudos em Terapias Inovadoras LTDA. Curitiba PR Brazil 80030-110
    63 Instituto de Dermatologia e Estética do Brasil LTDA Rio de Janeiro RJ Brazil 22470-220
    64 Hospital De Clinicas De Porto Alegre Porto Alegre RS Brazil 90035-003
    65 Associacao dos Funcionarios Públicos do Estado do Rio Grande do Sul - Hospital Ernesto Dornelles Porto Alegre RS Brazil 90160-093
    66 Pesquisare Saude S/S Ltda Santo Andre SP Brazil 09.080-110
    67 Fundacao do ABC - Faculdade de Medicina do ABC Santo Andre SP Brazil 09060-870
    68 IBPClin Pesquisa Clinica Rio de Janeiro Brazil 20241-180
    69 MC Asklepii" OOD Dupnitsa Bulgaria 2600
    70 MHAT "Dr. Tota Venkova" AD Gabrovo Bulgaria 5300
    71 "Center of skin-venereal diseases" EOOD, Sofia Sofia Bulgaria 1404
    72 "DCC Fokus-5-Medical Establishment for OutpatientCare"EOOD Sofia Bulgaria 1463
    73 "Mc Sinexus Sofia" Eood Sofia Bulgaria 1784
    74 ACIBADEM City Clinic Diagnostic-Consultative Center EOOD Sofia Bulgaria 1784
    75 "ACIBADEM City Clinic Medical Center Varna" EOOD Varna Bulgaria 9000
    76 Dermatology Research Institute Calgary Alberta Canada T1Y0B4
    77 Stratica Medical Edmonton Alberta Canada T5K 1X3
    78 Alberta Dermasurgery Center Edmonton Alberta Canada T6G1C3
    79 Wiseman Dermatology Research Inc. Winnipeg Manitoba Canada R3M 3Z4
    80 Karma Clinical Trials, Inc. St. John's Newfoundland and Labrador Canada A1A 4Y3
    81 CCA Medical Research Ajax Ontario Canada L1S 7K8
    82 SimcoDerm Medical and Surgical Dermatology Center Barrie Ontario Canada L4M 7G1
    83 Lynderm Research Inc. Markham Ontario Canada L3P 1X2
    84 DermEdge Research Mississauga Ontario Canada L5H 1G9
    85 Dermatology Ottawa Research Centre Ottawa Ontario Canada K2C 3N2
    86 SKiN Centre for Dermatology Peterborough Ontario Canada K9J 5K2
    87 Office of Dr. Paul Adam Scarborough Ontario Canada M1B 4Z8
    88 AvantDerm Toronto Ontario Canada M5A 3R6
    89 K. Papp Clinical Research Waterloo Ontario Canada N2J 1C4
    90 XLR8 Medical Research Inc. Windsor Ontario Canada N8W 1E6
    91 Centre de Recherche Dermatologique du Quebec Metropolitain (CRDQ) Quebec Canada G1V 4X7
    92 Centro Medico SkinMed Limitada Santiago Region Metropolitana Chile 7580206
    93 Clinica Dermacross S.A. Santiago Region Metropolitana Chile 7640881
    94 Centro Internacional de Estudios Clinicos - CIEC Santiago Region Metropolitana Chile 8420383
    95 Hospital Clinico Universidad de Chile Santiago Región Metropolitana Chile 8380456
    96 Beijing Friendship Hospital, Capital Medical University Beijing Beijing China 100050
    97 The Second Affiliated Hospital of Army Medical University, PLA Chongqing Chongqing China 400037
    98 The First Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong China 510080
    99 The Third Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong China 510630
    100 The University of Hong Kong - Shenzhen Hospital Shenzhen Guangdong China 518053
    101 Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology Wuhan Hubei China 430030
    102 The Second Xiangya Hospital of Central South University Changsha Hunan China 410011
    103 The Third Xiangya Hospital of Central South University Changsha Hunan China 410013
    104 The First Affiliated Hospital With Nanjing University Nanjing Jiangsu China 210000
    105 Dermatology Hospital of Jiangxi Province Nanchang Jiangxi China 330000
    106 Jinan Central Hospital Jinan Shandong China 250013
    107 Huashan Hospital Fudan University Shanghai Shanghai China 200040
    108 Tianjin Medical University General Hospital, Dermatological Department Tianjin Tianjin China 300052
    109 The First Affiliated Hospital of Zhejiang University School of Medicine/Dermatology and STD Dept Hangzhou Zhejiang China 310003
    110 The Second Affiliated Hospital of Zhejiang University School of Medicine/Dermatology Dept Hangzhou Zhejiang China 310009
    111 Zhejiang Provincial People's Hospital/Dermatology Department Hangzhou Zhejiang China 310014
    112 Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang China 310016
    113 Peking University First Hospital Beijing China 100034
    114 Shanghai Changzheng Hospital Shanghai China 200003
    115 Shanghai Dermatology Hospital Shanghai China 200443
    116 Charite - Universitaetsmedizin Berlin, Klinik fuer Dermatologie, Venerologie und Allergologie Berlin Germany 10117
    117 Hautzentrum Friedrichshain Studien Berlin Germany 10247
    118 Rothhaar Studien GmbH Berlin Germany 10783
    119 Klinikum Bielefeld Rosenhoehe Bielefeld Germany 33647
    120 Universitaetsklinikum Bonn Bonn Germany 53127
    121 Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden Dresden Germany 01307
    122 Universitaetsklinikum Erlangen Erlangen Germany 91054
    123 Universitaetsklinikum Essen Essen Germany 45147
    124 SRH Wald-Klinikum Gera GmbH Gera Germany 07548
    125 Universitätsklinikum und Poliklinik für Dermatologie und Venerologie Halle Germany 06120
    126 Klinische Forschung Hamburg GmbH Hamburg Germany 20253
    127 TFS Trial Form Support GmbH Hamburg Germany 20537
    128 Katholisches Kinderkrankenhaus Wilhemstift Hamburg Germany 22149
    129 MENSINGDERMA research GmbH Hamburg Germany 22391
    130 Medizinische Hochschule Hannover Hannover Germany 30625
    131 Praxis Dr. med. Beate Schwarz Langenau Germany 89129
    132 Universitaetsklinikum Schleswig-Holstein Luebeck Germany 23538
    133 Hautaerztliche Gemeinschaftspraxis Dres. Leitz und Kollegen Stuttgart Germany 70178
    134 Soroka University Medical Center Beer Sheva Israel 8410101
    135 Rambam Health Care Campus Haifa Israel 3109601
    136 Rabin Medical Center Petah Tikva Israel 4941492
    137 The Chaim Sheba Medical Center Ramat-Gan Israel 5265601
    138 Tel-Aviv Sourasky Medical Center Tel-Aviv Israel 6423906
    139 AOU Policlinico Sant'Orsola Malpighi Bologna BO Italy 40138
    140 Universita' degli Studi G. D'Annunzio -CeSi-MeT Chieti CH Italy 66100
    141 IFO Istituto Dermatologico San Gallicano IRCCS, Roma RM Italy 00144
    142 Ospedale Cristo Re Roma Rome Italy 00167
    143 Azienda Ospedaliero Universitaria San Martino di Genova Genova Italy 16132
    144 Ospedale Luigi Sacco Milano Italy 20157
    145 Prof. Giovanni Pellacani AOU Policlinico di Modena Struttura Complessa di Dermatologia Modena Italy 41124
    146 Universita del Sacro Cuore, Policlinico Agostino Gemelli, Istituto Di Dermatologia Rome Italy 00168
    147 Riga 1st Hospital, Clinic of Dermatology and STD Riga Latvia LV - 1001
    148 Health and Aesthetics Ltd Riga Latvia LV-1009
    149 Health Centre 4 Ltd, Dermatology Clinics Riga Latvia LV-1013
    150 Outpatient Clinic Of Ventspils Ventspils Latvia LV3601
    151 Arke Estudios Clinicos S.A. de C.V. Cuauhtemoc Ciudad DE Mexico Mexico 06700
    152 Phylasis Clinicas Research S. de R.L. de C.V. Cuautitlan Izcalli Estado DE Mexico Mexico 54769
    153 JM Research SC Cuernavaca Morelos Mexico 62290
    154 Centro de Dermatologia de Monterrey Monterrey Nuevo LEON Mexico 64460
    155 Derma Norte del Bajio S.C Aguascalientes Mexico 20127
    156 Centro de Investigacion Integral Medivest S.C. Chihuahua Mexico 31203
    157 Universitair Medisch Centrum (UMC) Utrecht Utrecht Netherlands 3584 CX
    158 Nasz Lekarz Osrodek Badan Klinicznych Bydgoszcz Poland 85-065
    159 Centrum Medyczne SENSEMED Chorzow Poland 41-500
    160 Copernicus Podmiot Leczniczy Sp. z.o.o., Oddzial Dermatologii Gdansk Poland 80-152
    161 Uniwersyteckie Centrum Kliniczne, Klinika Dermatologii, Wenerologii i Alergologii Gdansk Poland 80-214
    162 Silmedic Sp. z o.o., Oddzial w Katowicach Katowice Poland 40-282
    163 Centrum Medyczne Angelius Provita Katowice Poland 40-611
    164 Pro Familia Altera Sp. z o.o. Katowice Poland 40-648
    165 Malopolskie Centrum Kliniczne Krakow Poland 30-149
    166 Centrum Badan Klinicznych JCI Krakow Poland 30-348
    167 Krakowskie Centrum Medyczne Sp. z o.o. Krakow Poland 31-501
    168 Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna Lodz Poland 90-242
    169 NZOZ "DERMED" Centrum Medyczne Sp. z o.o. - Oddzial w Lodzi Lodz Poland 90-265
    170 O?rodek Bada? Klinicznych Appletreeclinics Lodz Poland 90-349
    171 Dermoklinika-Centrum Medyczne s.c. Lodz Poland 90-436
    172 KO-MED Centra Kliniczne Lublin II Lublin Poland 20-362
    173 Dermedic Jacek Zdybski Ostrowiec Swietokrzyski Poland 27-400
    174 Laser Clinic S.C. dr Tomasz Kochanowski dr Andrzej Krolicki Szczecin Poland 70-332
    175 Alergo-Med Specjalistyczna Przychodnia Lekarska Sp. z o.o. Tarnow Poland 33-100
    176 Synexus Polska Sp. z o.o. Oddzial w Warszawie Warszawa Poland 01-192
    177 MTZ Clinical Research Sp. z o.o. Warszawa Poland 02-106
    178 Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie Warszawa Poland 02-507
    179 RCMed Oddzial Warszawa Warszawa Poland 02-657
    180 Klinika Ambroziak Sp. z o.o. Warszawa Poland 02-758
    181 ETG Warszawa Warszawa Poland 02-793
    182 Wojskowy Instytut Medyczny, Klinika Dermatologiczna Warszawa Poland 04-141
    183 Synexus Polska Sp. z o.o. Oddzial we Wroclawiu Wroclaw Poland 50-381
    184 Lukasz Matusiak "4Health' Wroclaw Poland 50-566
    185 Kliniczny Oddzial Chorob Wewnetrznych, Dermatologii i Alergologii Zabrze Poland 41-800
    186 SC Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL Brasov JUD. Brasov Romania 500283
    187 Cabinet Medical de Dermatovenerologie Prof. Dr. Orasan Remus Ioan Cluj-Napoca Jud. Cluj Romania 400105
    188 SC Delta Health Care SRL Bucuresti Romania 014142
    189 SBIH "Chelyabinsk Regional Clinical Dermatovenerology dispensary" Chelyabinsk Russian Federation 454048
    190 Limited Liability Company "Medical Center "Rheuma-Med" Kemerovo Russian Federation 650070
    191 Clinic of FSBEI HE Kirov SMU MOH Russia Kirov Russian Federation 610014
    192 FSBI "State Research Centre of Dermatovenereology and Cosmetology" MoH RF Moscow Russian Federation 107076
    193 NRC Institute of Immunology FMBA of Russia Moscow Russian Federation 115478
    194 SBI RR "Skin and Venereal Dispensary" Rostov-on-Don Russian Federation 344007
    195 SBI RR "Regional Clinical Skin and Veneral Dispensary" Ryazan Russian Federation 390046
    196 Medical Research Institute, LLC Saint Petersburg Russian Federation 196084
    197 LLC "Pierre Wolkenstein Clinic of Skin Diseases" Saint-Petersburg Russian Federation 191123
    198 Vitiligo center Saint-Petersburg Russian Federation 191123
    199 SPb SBIH "Dermatovenerologic Dispensary #10 - Clinic of dermatology and venerology" Saint-Petersburg Russian Federation 194021
    200 FSBEI HE "St. Petersburg State Pediatric Medical University" MoH RF Saint-Petersburg Russian Federation 194100
    201 Limited Liability Company "Sanavita" Saint-Petersburg Russian Federation 195257
    202 FSBEI HE I.P.Pavlov SPbSMU MOH Russia Saint-Petersburg Russian Federation 197022
    203 RSBIH "Smolensk Regional Clinical Hospital" Smolensk Russian Federation 214018
    204 Military Medical Academy Belgrade Serbia 11000
    205 Clinical Centre Nis Nis Serbia 18000
    206 General Hospital Pancevo Pancevo Serbia 26000
    207 Fakultna Nemocnica s Poliklinikou F. D. Roosevelta Banska Bystrica Banska Bystrica Slovakia 975 17
    208 Narodny ustav detskych chorob, Detska dermatovenerologicka klinika LF UK a NUDCH Bratislava Slovakia 833 40
    209 BeneDerma s.r.o. Bratislava Slovakia 841 02
    210 Derma therapy spol. s.r.o, Dermatovenerologicka ambulancia Bratislava Slovakia 85101
    211 Nemocnica Kosice-Saca, a.s., 1. sukromna nemocnica, Kozna ambulancia Kosice-Saca Slovakia 040 15
    212 Pedi-Derma s.r.o., Dermatovenerologicka ambulancia Kosice Slovakia 04001
    213 Derma-beauty, s.r.o., Dermatovenerologicka ambulancia Nitra Slovakia 949 01
    214 SANARE spol. s.r.o., Dermatovenerologicka ambulancia Svidnik Slovakia 089 01
    215 Hospital Universitari Germans Trias i Pujol Badalona Barcelona Spain 08916
    216 Hospital Sant Joan de Deu Esplugues de Llobregat Barcelona Spain 08950
    217 Hospital Universitario Puerta de Hierro de Majadahonda Majadahonda Madrid Spain 28222
    218 Hospital General Universitario de Alicante Alicante Spain 03010
    219 Hospital Clinic de Barcelona Barcelona Spain 08036
    220 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08041
    221 Hospital Universitario Reina Sofia Cordoba Spain 14004
    222 Hospital Universitario de La Princesa Madrid Spain 28006
    223 Hospital General Universitario Gregorio Maranon Madrid Spain 28007
    224 Hospital Universitario Infanta Leonor Madrid Spain 28031
    225 Hospital Universitario La Paz Madrid Spain 28046
    226 Hospital del Nino Jesus Madrid Spain 28089
    227 Hospital Universitario Virgen de la Macarena Sevilla Spain 41009
    228 Consorcio Hospital General Universitario de Valencia Valencia Spain 46014
    229 Hospital Universitario y Politecnico La Fe Valencia Spain 46026
    230 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 807
    231 Taipei Medical University-Shuang Ho Hospital New Taipei City Taiwan 23561
    232 Chung Shan Medical University Hospital Taichung City Taiwan R.O.C 402
    233 National Cheng-Kung University Hospital Tainan Taiwan 704
    234 National Taiwan University Hospital Taipei Taiwan 100
    235 Chang Gung Memorial Hospital Linkou Branch Taoyuan City Taiwan 333

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT03627767
    Other Study ID Numbers:
    • B7451014
    • JADE REGIMEN
    • 2018-000501-23
    • REGIMEN
    First Posted:
    Aug 13, 2018
    Last Update Posted:
    Sep 20, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Pfizer
    atopic dermatitis
    atopic eczema
    eczema
    JAK
    janus kinase
    Additional relevant MeSH terms:
    Dermatitis, Atopic
    Genetic Diseases, Inborn
    Skin Diseases, Genetic
    Dermatitis
    Eczema
    Skin Diseases
    Skin Diseases, Eczematous
    Hypersensitivity
    Immune System Diseases
    Hypersensitivity, Immediate
    Abrocitinib

    Study Results

    Participant Flow

    Recruitment Details Total 1235 participants were enrolled in 236 sites in 21 countries. Study started from 11 June 2018 and completed on 07 October 2020.
    Pre-assignment Detail Study Baseline: was defined as the last observation collected on or prior to Day 1 (first dose day) of study treatment. Randomization Baseline: was defined as the last observation collected between last dose of run-in treatment and Day 1 (first dose day) of randomized treatment. Rescue Baseline: was defined as the last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment.
    Arm/Group Title PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants received 12 weeks induction treatment of 200 milligram (mg) oral tablets (each tablet of 100 mg) PF-04965842 once daily (QD) during an OL run-in period. Responders at the end of the 12-week OL run-in period entered the 40 week, double-blind (DB), maintenance treatment period. Responder criteria was defined as a) achieving an Investigator's Global Assessment (IGA) of clear (0) or almost clear (1) (on a 5-point scale), b) a reduction from IGA baseline of greater than or equal to (>= 2) points, and c) reaching an Eczema Area and Severity Index (EASI)-75 response compared to baseline score. Baseline score was the IGA score and EASI score obtained prior to dosing on Day 1. Non-responders had a choice to enroll into the PF-04965842 Long Term Extension (LTE) study B7451015 (NCT03422822) otherwise, they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Period Title: Open-label (OL) Run-in Period (12 Weeks)
    STARTED 1235 0 0 0 0
    Treated 1233 0 0 0 0
    COMPLETED 798 0 0 0 0
    NOT COMPLETED 437 0 0 0 0
    Period Title: Open-label (OL) Run-in Period (12 Weeks)
    STARTED 0 267 265 266 0
    Participants Entered Rescue Period 0 208 109 44 0
    Completed After Entering Rescue Period 0 201 99 41 0
    Completed Without Entering Rescue Period 0 43 134 187 0
    COMPLETED 0 251 243 231 0
    NOT COMPLETED 0 16 22 35 0
    Period Title: Open-label (OL) Run-in Period (12 Weeks)
    STARTED 0 0 0 0 361
    Met Protocol-defined Flare Criteria 0 0 0 0 351
    COMPLETED 0 0 0 0 341
    NOT COMPLETED 0 0 0 0 20

    Baseline Characteristics

    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB Total
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Total of all reporting groups
    Overall Participants 267 265 266 798
    Age, Customized (Count of Participants)
    <18 years
    49
    18.4%
    49
    18.5%
    47
    17.7%
    145
    18.2%
    Between 18 and 65 years
    210
    78.7%
    206
    77.7%
    207
    77.8%
    623
    78.1%
    >=65 years
    8
    3%
    10
    3.8%
    12
    4.5%
    30
    3.8%
    Sex: Female, Male (Count of Participants)
    Female
    126
    47.2%
    117
    44.2%
    116
    43.6%
    359
    45%
    Male
    141
    52.8%
    148
    55.8%
    150
    56.4%
    439
    55%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    65
    24.3%
    62
    23.4%
    52
    19.5%
    179
    22.4%
    Not Hispanic or Latino
    200
    74.9%
    203
    76.6%
    214
    80.5%
    617
    77.3%
    Unknown or Not Reported
    2
    0.7%
    0
    0%
    0
    0%
    2
    0.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    1.5%
    2
    0.8%
    1
    0.4%
    7
    0.9%
    Asian
    38
    14.2%
    41
    15.5%
    45
    16.9%
    124
    15.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    14
    5.2%
    9
    3.4%
    10
    3.8%
    33
    4.1%
    White
    209
    78.3%
    208
    78.5%
    204
    76.7%
    621
    77.8%
    More than one race
    2
    0.7%
    3
    1.1%
    5
    1.9%
    10
    1.3%
    Unknown or Not Reported
    0
    0%
    2
    0.8%
    1
    0.4%
    3
    0.4%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Loss of Response: Double-blind (DB) Period
    Description Percentage of participants with loss of response requiring rescue treatment during double blind period was determined. Loss of response denoted as flare and was define as a loss of at least 50% of EASI total score at Week 12 and with an IGA score of 2 or higher. EASI quantifies severity of participant's atopic dermatitis (AD) based on both severity of lesion clinical signs and % of body surface area (BSA) affected. EASI is a composite scoring by AD clinical evaluator of degree of erythema, induration/papulation, excoriation, and lichenification for each of 4 body regions. EASI total score range from 0.0 to 72.0, with higher scores representing greater severity of AD. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores = more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate and 4 = severe.
    Time Frame From Day 1 of up to Week 40 of double blind period

    Outcome Measure Data

    Analysis Population Description
    Full analysis set-randomized (FAS-RA) included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 265 266
    Number [percentage of participants]
    77.5
    29%
    39.6
    14.9%
    16.5
    6.2%
    2. Secondary Outcome
    Title Time to First Loss of Response Based on Investigator's Global Assessment (IGA) Score of 2 or Higher: Double-blind Period
    Description Time (in days) to loss of response based on achieving IGA >=2 (for the first time) as measured from date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue). IGA assesses severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep, dark red lesions.
    Time Frame From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window +/- 7 Days)

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least one dose of study medication within the double-blind phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment. Here, Overall 'Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 247 183 145
    Median (95% Confidence Interval) [days]
    27.0
    (26.0)
    78.0
    (32.0)
    201.0
    (177.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.35
    Confidence Interval (2-Sided) 95%
    0.286 to 0.424
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.22
    Confidence Interval (2-Sided) 95%
    0.176 to 0.270
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.63
    Confidence Interval (2-Sided) 95%
    0.503 to 0.780
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Weeks 12, 16, 28, 40, and 52: Double-blind Period
    Description IGA assessed severity of AD on a 5-point scale (0 to 4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep dark red lesions.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for the specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 264 266
    Week 12
    99.6
    37.3%
    99.6
    37.6%
    99.2
    37.3%
    Week 16
    15.4
    5.8%
    55.5
    20.9%
    77.8
    29.2%
    Week 28
    10.5
    3.9%
    45.0
    17%
    61.8
    23.2%
    Week 40
    10.6
    4%
    42.3
    16%
    57.1
    21.5%
    Week 52
    11.7
    4.4%
    36.8
    13.9%
    54.1
    20.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9495
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -1.0 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.5717
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.6 to 0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.7 to 0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 40.5
    Confidence Interval (2-Sided) 95%
    33.1 to 47.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 62.6
    Confidence Interval (2-Sided) 95%
    56.1 to 69.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 22.1
    Confidence Interval (2-Sided) 95%
    14.3 to 29.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 35.1
    Confidence Interval (2-Sided) 95%
    28.1 to 42.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 51.5
    Confidence Interval (2-Sided) 95%
    44.6 to 58.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 16.5
    Confidence Interval (2-Sided) 95%
    8.1 to 24.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 32.2
    Confidence Interval (2-Sided) 95%
    25.2 to 39.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 46.9
    Confidence Interval (2-Sided) 95%
    39.9 to 53.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 14.2
    Confidence Interval (2-Sided) 95%
    5.9 to 22.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 25.5
    Confidence Interval (2-Sided) 95%
    18.5 to 32.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 42.5
    Confidence Interval (2-Sided) 95%
    35.3 to 49.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.1
    Confidence Interval (2-Sided) 95%
    8.6 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=50% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema [E], induration/papulation [I], excoriation [Ex] and lichenification [L]) was scored separately for each of 4 body regions (head and neck [h], upper limbs [u], trunk [t] [including axillae and groin] and lower limbs [l] [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); where A = area score. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 264 266
    Week 12
    100.0
    37.5%
    100.0
    37.7%
    100.0
    37.6%
    Week 16
    40.8
    15.3%
    83.3
    31.4%
    96.2
    36.2%
    Week 28
    22.8
    8.5%
    68.1
    25.7%
    85.9
    32.3%
    Week 40
    16.6
    6.2%
    57.3
    21.6%
    74.9
    28.2%
    Week 52
    15.9
    6%
    50.8
    19.2%
    71.2
    26.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    0.0 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions. P-value was adjusted by disease severity at baseline and randomization strata.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    0.0 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    0.0 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 42.7
    Confidence Interval (2-Sided) 95%
    35.3 to 50.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 55.4
    Confidence Interval (2-Sided) 95%
    49.1 to 61.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 12.9
    Confidence Interval (2-Sided) 95%
    7.9 to 17.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 45.5
    Confidence Interval (2-Sided) 95%
    37.9 to 53.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 63.0
    Confidence Interval (2-Sided) 95%
    56.4 to 69.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.7
    Confidence Interval (2-Sided) 95%
    10.7 to 24.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 41.0
    Confidence Interval (2-Sided) 95%
    33.6 to 48.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 58.3
    Confidence Interval (2-Sided) 95%
    51.3 to 65.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.5
    Confidence Interval (2-Sided) 95%
    9.6 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 35.3
    Confidence Interval (2-Sided) 95%
    27.8 to 42.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 55.3
    Confidence Interval (2-Sided) 95%
    48.3 to 62.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 20.3
    Confidence Interval (2-Sided) 95%
    12.1 to 28.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 264 266
    Week 12
    99.2
    37.2%
    100.0
    37.7%
    99.6
    37.4%
    Week 16
    27.0
    10.1%
    76.0
    28.7%
    92.5
    34.8%
    Week 28
    18.0
    6.7%
    60.4
    22.8%
    80.5
    30.3%
    Week 40
    15.1
    5.7%
    54.2
    20.5%
    71.8
    27%
    Week 52
    14.0
    5.2%
    46.5
    17.5%
    65.8
    24.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1848
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -0.3 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.5971
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.9 to 1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 49.4
    Confidence Interval (2-Sided) 95%
    42.0 to 56.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 65.5
    Confidence Interval (2-Sided) 95%
    59.3 to 71.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 16.3
    Confidence Interval (2-Sided) 95%
    10.3 to 22.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 42.7
    Confidence Interval (2-Sided) 95%
    35.2 to 50.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 62.6
    Confidence Interval (2-Sided) 95%
    56.0 to 69.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 19.8
    Confidence Interval (2-Sided) 95%
    12.3 to 27.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 39.5
    Confidence Interval (2-Sided) 95%
    32.1 to 46.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 56.7
    Confidence Interval (2-Sided) 95%
    49.8 to 63.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.4
    Confidence Interval (2-Sided) 95%
    9.3 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 33.0
    Confidence Interval (2-Sided) 95%
    25.7 to 40.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 51.7
    Confidence Interval (2-Sided) 95%
    44.6 to 58.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 19.2
    Confidence Interval (2-Sided) 95%
    10.8 to 27.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=90% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score = 0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 264 266
    Week 12
    84.6
    31.7%
    87.1
    32.9%
    86.4
    32.5%
    Week 16
    13.9
    5.2%
    51.3
    19.4%
    77.1
    29%
    Week 28
    10.5
    3.9%
    46.9
    17.7%
    64.5
    24.2%
    Week 40
    12.1
    4.5%
    41.5
    15.7%
    58.7
    22.1%
    Week 52
    10.6
    4%
    37.6
    14.2%
    54.5
    20.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3994
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 2.6
    Confidence Interval (2-Sided) 95%
    -3.3 to 8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.5542
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    -4.1 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -6.5 to 5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 37.5
    Confidence Interval (2-Sided) 95%
    30.2 to 44.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 63.3
    Confidence Interval (2-Sided) 95%
    56.8 to 69.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 25.5
    Confidence Interval (2-Sided) 95%
    17.7 to 33.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 36.9
    Confidence Interval (2-Sided) 95%
    29.9 to 44.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 54.2
    Confidence Interval (2-Sided) 95%
    47.3 to 61.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.2
    Confidence Interval (2-Sided) 95%
    8.9 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 29.8
    Confidence Interval (2-Sided) 95%
    22.7 to 37.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 46.7
    Confidence Interval (2-Sided) 95%
    39.6 to 53.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 16.9
    Confidence Interval (2-Sided) 95%
    8.5 to 25.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 27.4
    Confidence Interval (2-Sided) 95%
    20.4 to 34.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 43.8
    Confidence Interval (2-Sided) 95%
    36.7 to 50.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 16.8
    Confidence Interval (2-Sided) 95%
    8.4 to 25.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=100% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 267 264 266
    Week 12
    30.5
    11.4%
    30.3
    11.4%
    28.3
    10.6%
    Week 16
    3.7
    1.4%
    15.2
    5.7%
    28.9
    10.9%
    Week 28
    4.1
    1.5%
    16.5
    6.2%
    30.2
    11.4%
    Week 40
    4.5
    1.7%
    15.8
    6%
    30.1
    11.3%
    Week 52
    4.5
    1.7%
    18.6
    7%
    28.8
    10.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9313
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -7.5 to 8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.6043
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -9.8 to 5.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -10.0 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 11.6
    Confidence Interval (2-Sided) 95%
    6.6 to 16.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 25.3
    Confidence Interval (2-Sided) 95%
    19.4 to 31.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 13.5
    Confidence Interval (2-Sided) 95%
    6.6 to 20.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 12.9
    Confidence Interval (2-Sided) 95%
    7.7 to 18.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 26.0
    Confidence Interval (2-Sided) 95%
    19.9 to 32.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 13.4
    Confidence Interval (2-Sided) 95%
    6.3 to 20.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 11.7
    Confidence Interval (2-Sided) 95%
    6.5 to 16.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 25.7
    Confidence Interval (2-Sided) 95%
    19.6 to 31.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 14.1
    Confidence Interval (2-Sided) 95%
    7.0 to 21.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 14.6
    Confidence Interval (2-Sided) 95%
    9.2 to 20.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 24.5
    Confidence Interval (2-Sided) 95%
    18.4 to 30.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 10.0
    Confidence Interval (2-Sided) 95%
    2.7 to 17.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percentage of Participants With Greater Than or Equal 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated worse disease status.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 258 254 250
    Week 12
    82.2
    30.8%
    84.0
    31.7%
    81.9
    30.8%
    Week 16
    15.9
    6%
    54.6
    20.6%
    75.6
    28.4%
    Week 28
    11.6
    4.3%
    45.0
    17%
    66.9
    25.2%
    Week 40
    10.1
    3.8%
    39.4
    14.9%
    55.7
    20.9%
    Week 52
    8.3
    3.1%
    27.6
    10.4%
    49.0
    18.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.6082
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 1.8
    Confidence Interval (2-Sided) 95%
    -5.0 to 8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9640
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -6.7 to 7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -9.1 to 4.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 38.9
    Confidence Interval (2-Sided) 95%
    31.2 to 46.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 59.7
    Confidence Interval (2-Sided) 95%
    52.7 to 66.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 20.9
    Confidence Interval (2-Sided) 95%
    12.7 to 29.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 33.9
    Confidence Interval (2-Sided) 95%
    26.6 to 41.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 55.3
    Confidence Interval (2-Sided) 95%
    48.2 to 62.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 21.7
    Confidence Interval (2-Sided) 95%
    13.2 to 30.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 29.7
    Confidence Interval (2-Sided) 95%
    22.7 to 36.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 45.5
    Confidence Interval (2-Sided) 95%
    38.4 to 52.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 16.0
    Confidence Interval (2-Sided) 95%
    7.4 to 24.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 19.9
    Confidence Interval (2-Sided) 95%
    13.0 to 26.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 40.5
    Confidence Interval (2-Sided) 95%
    32.8 to 48.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 20.9
    Confidence Interval (2-Sided) 95%
    11.8 to 30.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percent Change From Baseline in Body Surface Area (BSA) at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description 4 body regions evaluated: head and neck, upper limbs, trunk (including axillae, groin/genitals), lower limbs (including buttocks) excluding scalp, palms, soles. BSA calculated by handprint method. Number (No) of handprints (size of participant's hand with fingers in closed position) fitting in affected area of a body region was estimated. Maximum No of handprints were 10, 20, 30, 40 for head and neck, upper limbs, trunk, and lower limbs respectively. Surface area (SA) of body region equivalent to 1 handprint: 1 handprint=10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. %Change BSA for a body region was calculated as=total No of handprints in a body region* %SA equivalent to 1 handprint. %BSA for an individual: arithmetic mean of %BSA of all 4 body regions, ranged from 0-100%, higher values=greater AD severity.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 266 264 265
    Change at Week 12
    -95.6
    -96.7
    -96.7
    Change at Week 16
    -68.5
    -90.9
    -96.3
    Change at Week 28
    -85.2
    -93.8
    -96.4
    Change at Week 40
    -91.2
    -95.8
    -96.8
    Change at Week 52
    -91.5
    -96.9
    -96.9
    10. Secondary Outcome
    Title Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3); severity scores added to give B (0-18). C: pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 265 264 265
    Change at Week 12
    -84.0
    -84.4
    -84.4
    Change at Week 16
    -50.4
    -71.7
    -83.6
    Change at Week 28
    -63.4
    -77.8
    -83.8
    Change at Week 40
    -74.4
    -77.1
    -84.6
    Change at Week 52
    -73.3
    -82.5
    -83.2
    11. Secondary Outcome
    Title Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch and Sleep Loss at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region-head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 264 264 261
    Pruritus VAS: Change at Week 12
    -6.1
    -6.1
    -6.1
    Pruritus VAS: Change at Week 16
    3.4
    1.2
    0.2
    Pruritus VAS: Change at Week 28
    2.4
    1.1
    0.5
    Pruritus VAS: Change at Week 40
    2.2
    1.2
    0.4
    Pruritus VAS: Change at Week 52
    1.8
    1.3
    0.5
    Sleep Loss VAS: Change at Week 12
    -5.0
    -5.0
    -5.1
    Sleep Loss VAS: Change at Week 16
    2.3
    0.5
    0.0
    Sleep Loss VAS: Change at Week 28
    1.3
    0.6
    0.2
    Sleep Loss VAS: Change at Week 40
    1.3
    0.6
    0.2
    Sleep Loss VAS: Change at Week 52
    1.2
    0.9
    0.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Pruritus VAS: Week 12: The least squares mean (LSM) differences between treatment groups were derived from the statistical model. Mixed model repeated measure (MMRM) contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9207
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9998
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -3.6 to -2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Pruritus VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -2.0 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.9 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Pruritus VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0039
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.7 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.3 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Pruritus VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1488
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0003
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -2.0 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Pruritus VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Sleep Loss VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9294
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4081
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Sleep Loss VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -2.1 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.3
    Confidence Interval (2-Sided) 95%
    -2.7 to -2.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -0.9 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Sleep Loss VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0035
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -0.8 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Sleep Loss VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0136
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Sleep Loss VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.2887
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0025
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Sleep Loss VAS: Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.0 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title Percentage of Participants With >=50% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 266 264 266
    Week 12
    97.4
    36.5%
    98.5
    37.2%
    97.0
    36.5%
    Week 16
    25.6
    9.6%
    72.0
    27.2%
    89.1
    33.5%
    Week 28
    15.8
    5.9%
    56.8
    21.4%
    75.7
    28.5%
    Week 40
    14.4
    5.4%
    51.2
    19.3%
    69.0
    25.9%
    Week 52
    14.8
    5.5%
    44.6
    16.8%
    65.8
    24.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4244
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 1.0
    Confidence Interval (2-Sided) 95%
    -1.4 to 3.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.8092
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -3.1 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -4.1 to 1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 46.7
    Confidence Interval (2-Sided) 95%
    39.2 to 54.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 63.6
    Confidence Interval (2-Sided) 95%
    57.2 to 70.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.0
    Confidence Interval (2-Sided) 95%
    10.4 to 23.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 41.3
    Confidence Interval (2-Sided) 95%
    33.9 to 48.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 59.9
    Confidence Interval (2-Sided) 95%
    53.1 to 66.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18.7
    Confidence Interval (2-Sided) 95%
    10.8 to 26.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 37.0
    Confidence Interval (2-Sided) 95%
    29.6 to 44.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 54.6
    Confidence Interval (2-Sided) 95%
    47.6 to 61.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 17.7
    Confidence Interval (2-Sided) 95%
    9.4 to 26.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 30.0
    Confidence Interval (2-Sided) 95%
    22.6 to 37.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 50.9
    Confidence Interval (2-Sided) 95%
    43.8 to 58.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 21.1
    Confidence Interval (2-Sided) 95%
    12.8 to 29.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Percentage of Participants With >=75% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 266 264 266
    Week 12
    73.6
    27.6%
    75.0
    28.3%
    71.3
    26.8%
    Week 16
    9.4
    3.5%
    38.3
    14.5%
    67.3
    25.3%
    Week 28
    7.5
    2.8%
    37.8
    14.3%
    56.3
    21.2%
    Week 40
    8.3
    3.1%
    32.7
    12.3%
    47.7
    17.9%
    Week 52
    7.6
    2.8%
    31.8
    12%
    45.9
    17.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.7232
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -6.1 to 8.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.5694
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -9.8 to 5.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -3.7
    Confidence Interval (2-Sided) 95%
    -11.2 to 3.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 29.0
    Confidence Interval (2-Sided) 95%
    22.2 to 35.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 57.9
    Confidence Interval (2-Sided) 95%
    51.2 to 64.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 28.9
    Confidence Interval (2-Sided) 95%
    20.8 to 37.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 30.5
    Confidence Interval (2-Sided) 95%
    23.9 to 37.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 48.9
    Confidence Interval (2-Sided) 95%
    42.1 to 55.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18.2
    Confidence Interval (2-Sided) 95%
    9.8 to 26.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 25.0
    Confidence Interval (2-Sided) 95%
    18.4 to 31.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 39.6
    Confidence Interval (2-Sided) 95%
    32.7 to 46.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 14.5
    Confidence Interval (2-Sided) 95%
    6.3 to 22.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 24.7
    Confidence Interval (2-Sided) 95%
    18.1 to 31.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 38.5
    Confidence Interval (2-Sided) 95%
    31.6 to 45.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 13.9
    Confidence Interval (2-Sided) 95%
    5.6 to 22.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description IGA assessed severity of AD on a 5-point scale (0-4, higher scores indicated more severity), reflecting global consideration of erythema, induration and scaling. Where, 0=clear, AD is cleared; 1 = almost clear, AD not entirely cleared, light pink residual lesions; 2 = mild, AD with light red lesions; 3 = moderate, AD with red lesions; 4 = severe, AD with deep, dark red lesions.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set-rescue (FAS-RE) included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 342
    Rescue Week 2
    30.7
    11.5%
    Rescue Week 4
    54.6
    20.4%
    Rescue Week 8
    60.2
    22.5%
    Rescue Week 12
    64.1
    24%
    15. Secondary Outcome
    Title Percent Change From Rescue Baseline in Total Eczema Area and Severity Index (EASI) Score at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description EASI quantifies severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll). Total EASI score ranged from 0.0 to 72.0, higher scores=greater severity of AD.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 348
    Change at Rescue Week 2
    -71.1
    (-73.7)
    Change at Rescue Week 4
    -82.0
    (-84.2)
    Change at Rescue Week 8
    -86.4
    (-88.2)
    Change at Rescue Week 12
    -87.3
    (-89.4)
    16. Secondary Outcome
    Title Percentage of Participants Achieving Greater Than or Equal to 4 Points Improvement From Rescue Baseline in Peak Pruritus Numeric Rating Scale (PP-NRS) at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 272
    Rescue Week 2
    56.6
    21.2%
    Rescue Week 4
    63.2
    23.7%
    Rescue Week 8
    67.2
    25.2%
    Rescue Week 12
    56.2
    21%
    17. Secondary Outcome
    Title Percent Change From Rescue Baseline in Percent Body Surface Area (BSA) at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description 4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin/genitals) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Overall % BSA for an individual % BSA of all 4 body regions, ranged from 0 to 100%, with higher values representing greater severity of AD.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 348
    Change at Rescue Week 2
    -62.8
    Change at Rescue Week 4
    -76.4
    Change at Rescue Week 8
    -82.1
    Change at Rescue Week 12
    -83.3
    18. Secondary Outcome
    Title Percent Change From Rescue Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) Score of Itch and Sleep Loss at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment.. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 347
    Pruritus VAS: Change at Rescue Week 2
    -57.3
    (-61.7)
    Pruritus VAS: Change at Rescue Week 4
    -67.5
    (-71.3)
    Pruritus VAS: Change at Rescue Week 8
    -68.6
    (-73.6)
    Pruritus VAS: Change at Rescue Week 12
    -67.3
    (-72.8)
    Sleep Loss VAS: Change at Rescue Week 2
    -62.5
    (-69.1)
    Sleep Loss VAS: Change at Rescue Week 4
    -72.4
    (-78.6)
    Sleep Loss VAS: Change at Rescue Week 8
    -75.8
    (-82.0)
    Sleep Loss VAS: Change at Rescue Week 12
    -74.5
    (-81.4)
    19. Secondary Outcome
    Title Percentage of Participants With 50% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 339
    Rescue Week 2
    55.0
    20.6%
    Rescue Week 4
    76.1
    28.5%
    Rescue Week 8
    79.6
    29.8%
    Rescue Week 12
    79.8
    29.9%
    20. Secondary Outcome
    Title Percentage of Participants With 75% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period
    Description SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 used to calculate BSA affected by AD as % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; genitals 1%. Score of each body region added to determine A (0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2), severe (3). Severity scores added to give B (0-18). C: pruritus and sleep loss, each were scored by participant/caregiver using VAS where, 0=no itch/no sleep loss and 10=worst imaginable itch/sleep loss, higher scores=worse symptoms. Scores for itch and sleep loss added to give 'C' (0-20). SCORAD calculated as: A/5+7*B/2+C; range (0-103); higher values=worse outcome.
    Time Frame Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12

    Outcome Measure Data

    Analysis Population Description
    FAS-RE included all participants who met the protocol definition of a flare during the DB phase and received at least 1 dose of rescue treatment. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    Measure Participants 339
    Rescue Week 2
    16.9
    6.3%
    Rescue Week 4
    33.9
    12.7%
    Rescue Week 8
    44.4
    16.6%
    Rescue Week 12
    45.4
    17%
    21. Secondary Outcome
    Title Percentage of Participants Achieving Patient Global Assessment (PtGA) Response of 'Clear (0)' or 'Almost Clear (1)' and Greater Than or Equal to 2 Points Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description Participant responded to the following question: "Overall, how would you describe your Atopic Dermatitis right now?" on a 5-point scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable for specified time points.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 254 262 259
    Week 12
    61.7
    23.1%
    64.5
    24.3%
    59.7
    22.4%
    Week 16
    5.9
    2.2%
    29.8
    11.2%
    48.3
    18.2%
    Week 28
    6.3
    2.4%
    30.9
    11.7%
    46.9
    17.6%
    Week 40
    7.5
    2.8%
    26.1
    9.8%
    42.0
    15.8%
    Week 52
    7.6
    2.8%
    25.8
    9.7%
    39.7
    14.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4815
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    -5.3 to 11.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.6748
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -10.3 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value -5.1
    Confidence Interval (2-Sided) 95%
    -13.4 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 24.0
    Confidence Interval (2-Sided) 95%
    17.8 to 30.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 42.3
    Confidence Interval (2-Sided) 95%
    35.6 to 49.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18.4
    Confidence Interval (2-Sided) 95%
    10.2 to 26.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 24.6
    Confidence Interval (2-Sided) 95%
    18.2 to 31.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 40.5
    Confidence Interval (2-Sided) 95%
    33.7 to 47.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 15.9
    Confidence Interval (2-Sided) 95%
    7.6 to 24.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18.8
    Confidence Interval (2-Sided) 95%
    12.6 to 25.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 34.5
    Confidence Interval (2-Sided) 95%
    27.6 to 41.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 15.6
    Confidence Interval (2-Sided) 95%
    7.5 to 23.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 18.7
    Confidence Interval (2-Sided) 95%
    12.4 to 25.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage (PF-04965842 - Placebo) and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value was adjusted by disease severity at baseline and randomization strata.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 32.3
    Confidence Interval (2-Sided) 95%
    25.4 to 39.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: Difference in percentage and CI for difference were calculated based on the weighted average of difference for each randomization stratum and disease severity at baseline using the normal approximation of binomial proportions.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 13.7
    Confidence Interval (2-Sided) 95%
    5.6 to 21.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Change From Baseline in Dermatology Life Quality Index (DLQI) Score for Adults at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description DLQI was a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for adults, aged 18 years and above.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 217 215 217
    Change at Week 12
    -13.5
    (-13.9)
    -13.4
    (-13.8)
    -13.5
    (-14.0)
    Change at Week 16
    6.9
    (6.1)
    1.9
    (1.2)
    0.4
    (-0.2)
    Change at Week 28
    6.1
    (5.0)
    2.1
    (1.4)
    0.9
    (0.3)
    Change at Week 40
    4.4
    (3.0)
    2.5
    (1.7)
    1.1
    (0.5)
    Change at Week 52
    3.6
    (2.1)
    2.8
    (2.0)
    0.9
    (0.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.7373
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.8092
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.1
    Confidence Interval (2-Sided) 95%
    -6.1 to -4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -6.6
    Confidence Interval (2-Sided) 95%
    -7.6 to -5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -2.4 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -5.3 to -2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.2
    Confidence Interval (2-Sided) 95%
    -6.4 to -3.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.1 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0150
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.5 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -3.2
    Confidence Interval (2-Sided) 95%
    -4.7 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -2.3 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3616
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -2.4 to 0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0012
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -4.3 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -3.0 to -0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score for Adolescents at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description CDLQI is a 10-item questionnaire that measures the impact of skin disease on adolescents (aged 12-17 years) quality of life over the last week. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all , 1 = only a little, 2 = quite a lot, 3 = very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give CDLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of children.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here, 'Overall Number of Participants Analyzed' signifies number of participants evaluable for adolescents, aged 12-17 years.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 49 48 47
    Change at Week 12
    -9.8
    (-10.6)
    -9.2
    (-10.0)
    -9.3
    (-10.2)
    Change at Week 16
    5.9
    (4.4)
    1.7
    (0.5)
    -0.3
    (-1.4)
    Change at Week 28
    1.5
    (-0.2)
    1.6
    (0.6)
    0.4
    (-0.5)
    Change at Week 40
    2.1
    (0.3)
    1.7
    (0.7)
    0.0
    (-0.9)
    Change at Week 52
    2.3
    (0.3)
    1.3
    (0.0)
    0.4
    (-0.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3339
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.6
    Confidence Interval (2-Sided) 95%
    -0.6 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4653
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.5
    Confidence Interval (2-Sided) 95%
    -0.8 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -1.3 to 1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -4.3
    Confidence Interval (2-Sided) 95%
    -6.2 to -2.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -6.2
    Confidence Interval (2-Sided) 95%
    -8.2 to -4.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -3.6 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9083
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -1.8 to 2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.2439
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -3.0 to 0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.6 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.7405
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -2.4 to 1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0410
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -4.1 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -3.1 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4026
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -3.5 to 1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0944
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -4.2 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -2.5 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Primary Outcome
    Title Time to Loss of Response: Double-blind Period
    Description Time (in days) to loss of response based on achieving IGA >=2 was measured from date of first dose of randomized treatment until last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) and based on EASI, loss of at least 50% of EASI response at Week 12 and IGA score of 2 or higher. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores=more severity), reflecting global consideration of erythema, induration and scaling with scores 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. EASI composite score evaluates degree of erythema, induration/papulation, excoriation, and lichenification.
    Time Frame From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window was extended +/- 45 Days due to COVID 19)

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Missing event times were considered as right censored (CAR) on last date of randomized treatment. Here 'Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 207 105 44
    Median (95% Confidence Interval) [days]
    28.0
    323.0
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% confidence interval (CI).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate p-value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.27
    Confidence Interval (2-Sided) 95%
    0.211 to 0.341
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    0.070 to 0.136
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments A Cox regression model with treatment, age group and disease severity as stratification covariates was used to estimate the hazard ratio and the corresponding 95% CI.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments A stratified log-rank test with age group and disease severity as stratification variables was performed to evaluate P value.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.36
    Confidence Interval (2-Sided) 95%
    0.255 to 0.516
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    25. Secondary Outcome
    Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 266 263 264
    Change at Week 12
    -2.7
    (-3.0)
    -2.6
    (-2.9)
    -2.6
    (-2.9)
    Change at Week 16
    1.4
    (1.0)
    0.3
    (0.0)
    0.0
    (-0.3)
    Change at Week 28
    1.0
    (0.5)
    0.4
    (0.1)
    0.1
    (-0.2)
    Change at Week 40
    1.0
    (0.4)
    0.4
    (0.1)
    0.1
    (-0.3)
    Change at Week 52
    0.8
    (0.2)
    0.4
    (0.1)
    0.2
    (-0.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.7556
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.7484
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.1
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.1
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -1.9 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0242
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0012
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.6 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1240
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0107
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.6 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3139
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0853
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.7 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    26. Secondary Outcome
    Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Depression Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 266 263 264
    Change at Week 12
    -2.0
    (-2.3)
    -1.6
    (-1.9)
    -1.7
    (-2.0)
    Change at Week 16
    1.4
    (1.0)
    0.0
    (-0.3)
    0.0
    (-0.2)
    Change at Week 28
    0.7
    (0.2)
    0.3
    (0.0)
    0.1
    (-0.2)
    Change at Week 40
    0.8
    (0.2)
    -0.1
    (-0.4)
    0.2
    (-0.1)
    Change at Week 52
    0.4
    (-0.1)
    -0.1
    (-0.4)
    0.1
    (-0.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0674
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    0.0 to 0.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1437
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.1 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -1.8 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.4
    Confidence Interval (2-Sided) 95%
    -1.8 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1136
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.0 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0276
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -0.5 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0108
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.5 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0677
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.3
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1320
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.2975
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.3
    Confidence Interval (2-Sided) 95%
    -0.9 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.2
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    27. Secondary Outcome
    Title Change From Baseline in Patient Oriented Eczema Measure (POEM) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description POEM was a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item scored as following: no days = 0, 1-2 days = 1, 3-4 days = 2, 5-6 days = 3 and, every day = 4. The total POEM score ranges from 0 to 28, where higher score indicated greater severity.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 265 263 263
    Change at Week 12
    -15.4
    (-16.0)
    -15.8
    (-16.4)
    -15.4
    (-16.0)
    Change at Week 16
    9.8
    (8.9)
    3.7
    (3.0)
    0.6
    (-0.1)
    Change at Week 28
    8.3
    (6.9)
    3.7
    (2.8)
    1.6
    (0.8)
    Change at Week 40
    7.4
    (5.8)
    4.8
    (3.9)
    1.9
    (1.1)
    Change at Week 52
    7.3
    (5.4)
    4.9
    (3.8)
    2.2
    (1.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3531
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -1.3 to 0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.9282
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.8 to 0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -0.4 to 1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -6.1
    Confidence Interval (2-Sided) 95%
    -7.3 to -5.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -9.2
    Confidence Interval (2-Sided) 95%
    -10.3 to -8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -3.1
    Confidence Interval (2-Sided) 95%
    -4.0 to -2.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -4.6
    Confidence Interval (2-Sided) 95%
    -6.2 to -2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -6.7
    Confidence Interval (2-Sided) 95%
    -8.3 to -5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.1
    Confidence Interval (2-Sided) 95%
    -3.3 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0082
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -4.5 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.5
    Confidence Interval (2-Sided) 95%
    -7.4 to -3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -4.2 to -1.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0313
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -4.5 to -0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -5.1
    Confidence Interval (2-Sided) 95%
    -7.1 to -3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -4.1 to -1.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    28. Secondary Outcome
    Title Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period
    Description PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [darker or lighter], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participants had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition.
    Time Frame Baseline, Weeks 12, 16, 28, 40 and 52

    Outcome Measure Data

    Analysis Population Description
    FAS-RA included as all participants who were randomized at Week 12 and received at least 1 dose of study medication within DB phase. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure.
    Arm/Group Title PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Arm/Group Description Responders from OL run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study.
    Measure Participants 254 260 254
    Change at Week 12
    -4.1
    (-4.3)
    -4.2
    (-4.4)
    -4.2
    (-4.4)
    Change at Week 16
    2.1
    (1.9)
    0.8
    (0.6)
    0.1
    (-0.1)
    Change at Week 28
    2.3
    (2.0)
    1.0
    (0.8)
    0.1
    (-0.1)
    Change at Week 40
    2.0
    (1.7)
    1.0
    (0.8)
    0.3
    (0.0)
    Change at Week 52
    1.9
    (1.5)
    1.2
    (0.9)
    0.2
    (0.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.4832
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.4 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.6553
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.3 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 12: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -0.2 to 0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -1.5 to -1.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -2.2 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 16: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -0.9 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -1.7 to -1.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 28: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.0
    Confidence Interval (2-Sided) 95%
    -1.4 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.8
    Confidence Interval (2-Sided) 95%
    -2.2 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 40: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.1 to -0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0020
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.8
    Confidence Interval (2-Sided) 95%
    -1.2 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -1.7
    Confidence Interval (2-Sided) 95%
    -2.2 to -1.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB, PF-04965842 200 mg OL to PF-04965842 200 mg DB
    Comments Week 52: The LSM differences between treatment groups were derived from the statistical model. MMRM contained fixed factors of treatment, visit, treatment by visit interaction, baseline disease severity, randomization strata, baseline value and an unstructured covariance matrix.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LSM difference
    Estimated Value -0.9
    Confidence Interval (2-Sided) 95%
    -1.3 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame From screening up to 28 days after last dose of study treatment (maximum up to Week 56)
    Adverse Event Reporting Description Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who received at least 1 dose of study medication.
    Arm/Group Title PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
    Arm/Group Description Participants received 12 weeks induction treatment of 200 mg oral tablets (each tablet of 100 mg) PF-04965842 QD during an OL run-in period. Responders at the end of the 12-week open-label run-in period entered the 40 weeks, DB, maintenance treatment period. Responder criteria was defined as a) achieving an IGA of clear (0) or almost clear (1) (on a 5-point scale), b) a reduction from IGA baseline of >= 2 points, and c) reaching an EASI-75 response compared to baseline score. Baseline score was the IGA score and EASI score obtained prior to dosing on Day 1. Non-responders had a choice to enroll into the PF-04965842 LTE study B7451015 (NCT03422822) otherwise, they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received two placebo tablets matched to PF-04965842 orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period (RP). Flare was define as a loss of at least 50 percent (%) of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received a tablet of 100 mg PF-04965842 and a tablet of matching placebo orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Responders from open-label run-in period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during DB period for up to 40 weeks. Participants who met the protocol defined flare criteria entered in open-label rescue period. Flare was define as a loss of at least 50% of the EASI response at Week 12 and had an IGA score of 2 or higher. Participants who did not met the flare criteria had a choice to enroll into the LTE study, otherwise they were permanently discontinued from treatment and were followed-up for 4-week in this study. Participants who met the protocol defined flare criteria in DB period received 200 mg PF-04965842 (2 tablets of 100 mg each) orally QD during open-label Rescue Period for up to 12 weeks. After completing the 12-week rescue period, participants had the choice to enter the LTE study B7451015 (NCT03422822), if eligible. Participants who discontinued early from treatment, or who were otherwise ineligible for the LTE study, were followed-up for 4 week in this study.
    All Cause Mortality
    PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Serious Adverse Events
    PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/1233 (1.6%) 3/267 (1.1%) 9/265 (3.4%) 14/266 (5.3%) 4/351 (1.1%)
    Blood and lymphatic system disorders
    Microcytic anaemia 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Thrombocytopenia 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Congenital, familial and genetic disorders
    Vitello-intestinal duct remnant 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Eye disorders
    Cataract 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Retinal detachment 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Retinal vein thrombosis 0/1233 (0%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Ulcerative keratitis 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Inguinal hernia 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    General disorders
    Chest pain 1/1233 (0.1%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Immune system disorders
    Anaphylactic reaction 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Infections and infestations
    Abscess neck 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Appendicitis 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Cellulitis 2/1233 (0.2%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Diverticulitis 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Eczema herpeticum 0/1233 (0%) 0/267 (0%) 1/265 (0.4%) 1/266 (0.4%) 0/351 (0%)
    Gastrointestinal viral infection 0/1233 (0%) 1/267 (0.4%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Hepatitis E 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Periodontitis 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Peritonsillar abscess 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Pharyngitis 1/1233 (0.1%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 1/351 (0.3%)
    Pneumonia 1/1233 (0.1%) 1/267 (0.4%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Skin infection 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Injury, poisoning and procedural complications
    Humerus fracture 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Ligament injury 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Meniscus injury 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Multiple fractures 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Skin laceration 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Upper limb fracture 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Metabolism and nutrition disorders
    Hypokalaemia 1/1233 (0.1%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Musculoskeletal and connective tissue disorders
    Haemarthrosis 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Myositis 1/1233 (0.1%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Osteonecrosis 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Papillary thyroid cancer 0/1233 (0%) 0/267 (0%) 1/265 (0.4%) 0/266 (0%) 0/351 (0%)
    Nervous system disorders
    Seizure 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Renal and urinary disorders
    Ureterolithiasis 1/1233 (0.1%) 1/267 (0.4%) 0/265 (0%) 0/266 (0%) 1/351 (0.3%)
    Reproductive system and breast disorders
    Adnexa uteri cyst 0/1233 (0%) 0/267 (0%) 0/265 (0%) 1/266 (0.4%) 0/351 (0%)
    Metrorrhagia 1/1233 (0.1%) 0/267 (0%) 0/265 (0%) 0/266 (0%) 0/351 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis atopic 3/1233 (0.2%) 0/267 (0%) 1/265 (0.4%) 1/266 (0.4%) 2/351 (0.6%)
    Other (Not Including Serious) Adverse Events
    PF-04965842 200 mg OL PF-04965842 200 mg OL to Placebo DB PF-04965842 200 mg OL to PF-04965842 100 mg+Placebo DB PF-04965842 200 mg OL to PF-04965842 200 mg DB PF-04965842 200 mg Rescue Period
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 482/1233 (39.1%) 158/267 (59.2%) 130/265 (49.1%) 152/266 (57.1%) 75/351 (21.4%)
    Gastrointestinal disorders
    Nausea 199/1233 (16.1%) 44/267 (16.5%) 35/265 (13.2%) 49/266 (18.4%) 12/351 (3.4%)
    Vomiting 42/1233 (3.4%) 7/267 (2.6%) 12/265 (4.5%) 15/266 (5.6%) 4/351 (1.1%)
    Infections and infestations
    Nasopharyngitis 77/1233 (6.2%) 26/267 (9.7%) 27/265 (10.2%) 28/266 (10.5%) 17/351 (4.8%)
    Upper respiratory tract infection 63/1233 (5.1%) 26/267 (9.7%) 22/265 (8.3%) 22/266 (8.3%) 21/351 (6%)
    Investigations
    Blood creatine phosphokinase increased 43/1233 (3.5%) 11/267 (4.1%) 18/265 (6.8%) 25/266 (9.4%) 9/351 (2.6%)
    Nervous system disorders
    Headache 119/1233 (9.7%) 31/267 (11.6%) 24/265 (9.1%) 31/266 (11.7%) 12/351 (3.4%)
    Skin and subcutaneous tissue disorders
    Acne 68/1233 (5.5%) 19/267 (7.1%) 22/265 (8.3%) 31/266 (11.7%) 7/351 (2%)
    Dermatitis atopic 45/1233 (3.6%) 88/267 (33%) 56/265 (21.1%) 36/266 (13.5%) 13/351 (3.7%)

    Limitations/Caveats

    For outcome measure, Time to loss of response, the data collection window was extended for 45 days beyond the scheduled visit due to COVID 19.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT03627767
    Other Study ID Numbers:
    • B7451014
    • JADE REGIMEN
    • 2018-000501-23
    • REGIMEN
    First Posted:
    Aug 13, 2018
    Last Update Posted:
    Sep 20, 2021
    Last Verified:
    Sep 1, 2021