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Clinical Trial Results:
Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy and Safety of PF-04965842 Monotherapy in Subjects Aged 12 Years and Older, With Moderate to Severe Atopic Dermatitis

Summary
EudraCT number	2017-003651-29
Trial protocol	DE GB HU CZ PL
Global end of trial date	26 Mar 2019

Results information
Results version number	v1(current)
This version publication date	04 Oct 2019
First version publication date	04 Oct 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

B7451012

ISRCTN number

US NCT number

NCT03349060

WHO universal trial number (UTN)

Other trial identifiers

Alias Study Number: MONO-1, Alias Study Number: JADE MONO-1

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002312-PIP01-17

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

29 Apr 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Mar 2019

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of PF-04965842 compared with placebo in subjects aged 12 years and older with moderate to severe Atopic Dermatitis (AD).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Dec 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 51

Country: Number of subjects enrolled

Canada: 64

Country: Number of subjects enrolled

Czech Republic: 19

Country: Number of subjects enrolled

Germany: 64

Country: Number of subjects enrolled

Hungary: 12

Country: Number of subjects enrolled

Poland: 49

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

United States: 114

Worldwide total number of subjects

387

EEA total number of subjects

158

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

287

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects with age greater than or equal to (>=) 12 years with moderate to severe AD and a body weight of >=40 kilogram were enrolled in the study. Eligible subjects had an option to enter into a long-term extension (LTE) study after completing 12 weeks of treatment in this study.

Screening details

This study was conducted from 07-December-2017 to 26-March-2019 at 76 sites in 8 countries.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PF-04965842 100 mg

Arm description

Participants were randomized to receive a tablet of PF-04965842 100 milligram (mg) and a tablet of matching placebo orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Arm type

Experimental

Investigational medicinal product name

PF-04965842

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-04965842 100 mg tablet administered orally once daily for 12 weeks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

A tablet (matched to PF-04965842) of 100 mg administered orally once daily for 12 weeks.

PF-04965842 200 mg

Arm description

Participants were randomized to receive PF-04965842 200 mg (2 tablets of 100 mg each) orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Arm type

Experimental

Investigational medicinal product name

PF-04965842

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-04965842 200 mg, 2 tablets of 100 mg each administered orally once daily for 12 weeks.

Placebo

Arm description

Participants were randomized to receive 2 tablets of placebo matched to PF-04965842 100 mg orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets (matched to PF-04965842) of 100 mg each administered orally once daily for 12 weeks.

Number of subjects in period 1	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Started	156	154	77
Completed	135	137	61
Not completed	21	17	16
Consent withdrawn by subject	5	3	4
Withdrawal By Parent/Guardian	-	1	-
Adverse event	9	9	7
Medication error,no linked adverse event	-	-	1
Unspecified	2	1	-
Lost to follow-up	2	1	1
Lack of efficacy	1	-	2
Protocol deviation	2	2	1

Baseline characteristics

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Reporting group title

PF-04965842 100 mg

Reporting group description

Reporting group title

PF-04965842 200 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo	Total
Number of subjects	156	154	77	387
Age categorical
The full analysis set (FAS) included all randomized subjects who received at least 1 dose of study medication.
Units: Subjects
Adolescents (12-17 years)	34	33	17	84
Adults (18-64 years)	118	110	59	287
From 65-84 years	4	11	1	16
85 years and over	0	0	0	0
Age Continuous
The full analysis set included all randomized subjects who received at least 1 dose of study medication.
Units: years
arithmetic mean (standard deviation)	32.6 ± 15.4	33.0 ± 17.4	31.5 ± 14.4	-
Sex: Female, Male
The full analysis set included all randomized subjects who received at least 1 dose of study medication.
Units: Subjects
Female	66	73	28	167
Male	90	81	49	220
Ethnicity (NIH/OMB)
The full analysis set included all randomized subjects who received at least 1 dose of study medication.
Units: Subjects
Hispanic or Latino	10	4	6	20
Not Hispanic or Latino	144	149	71	364
Unknown or Not Reported	2	1	0	3
Race (NIH/OMB)
The full analysis set included all randomized subjects who received at least 1 dose of study medication.
Units: Subjects
American Indian or Alaska Native	1	4	1	6
Asian	26	26	6	58
Native Hawaiian or Other Pacific Islander	0	1	0	1
Black or African American	15	11	6	32
White	113	104	62	279
More than one race	1	6	1	8
Unknown or Not Reported	0	2	1	3

End points

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Reporting group title

PF-04965842 100 mg

Reporting group description

Reporting group title

PF-04965842 200 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12

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End point title

Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12

End point description

IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0=clear, no inflammatory signs of AD; 1=almost clear, AD not fully cleared-light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation and no oozing/crusting; 2=mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3=moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4=severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp. FAS=all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed”(N)=subjects evaluable for this end point.

End point type

Primary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	153	76
Units: percentage of subjects
number (not applicable)	23.7	43.8	7.9

Placebo Vs PF-04965842 100 mg

Statistical analysis description

The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0037 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

15.8

Confidence interval

level

95%

sides

2-sided

lower limit

6.8

upper limit

24.8

Notes
[1] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

26.2

upper limit

45.7

Notes
[2] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12

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End point title

Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12

End point description

EASI evaluates severity of subject's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD [erythema (E), induration/papulation (I), excoriation (Ex) and lichenification (L)] scored separately for each of 4 body regions (head and neck (h), upper limbs (u), trunk [including axillae and groin)] (t) and lower limbs [including buttocks] (l)) 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-<10%), 2(10-<30%), 3(30-<50%), 4(50-<70%), 5(70-<90%) and 6(90-100%). 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); (A =EASI area score) ranged from 0.0-72.0, higher scores=greater severity. FAS=all randomized subjects who received at least 1 dose of study medication. Here, N=subjects evaluable for this end point.

End point type

Primary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	153	76
Units: percentage of subjects
number (not applicable)	39.7	62.7	11.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

27.9

Confidence interval

level

95%

sides

2-sided

lower limit

17.4

upper limit

38.3

Notes
[3] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

40.5

upper limit

61.5

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)

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End point title

Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)

End point description

Subjects were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	147	147	74
Units: percentage of subjects
number (not applicable)
Week 2	20.4	45.6	2.7
Week 4	32.2	58.8	17.2
Week 8	34.3	59.9	14.4
Week 12	37.7	57.2	15.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: Each complete imputed data set was analyzed using the Cochran-Mantel-Haenszel (CMH) risk difference method adjusting by randomization strata, separately for each week. Results from multiply imputed data sets were combined using Rubin's rules to obtain treatment difference, 95% CI and p-value.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

10.2

upper limit

25.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: Each complete imputed data set was analyzed using the CMH risk difference method adjusting by randomization strata, separately for each week. Results from multiply imputed data sets were combined using Rubin's rules to obtain treatment difference, 95% CI and p-value.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

42.5

Confidence interval

level

95%

sides

2-sided

lower limit

33.6

upper limit

51.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: Each complete imputed data set was analyzed using the CMH risk difference method adjusting by randomization strata, separately for each week. Results from multiply imputed data sets were combined using Rubin's rules to obtain treatment difference, 95% CI and p-value.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0251

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.9

upper limit

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

41.1

Confidence interval

level

95%

sides

2-sided

lower limit

27.8

upper limit

54.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: Each complete imputed data set was analyzed using the CMH risk difference method adjusting by randomization strata, separately for each week. Results from multiply imputed data sets were combined using Rubin's rules to obtain treatment difference, 95% CI and p-value.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.4

upper limit

32.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

45.3

Confidence interval

level

95%

sides

2-sided

lower limit

32.7

upper limit

57.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: Each complete imputed data set was analyzed using the CMH risk difference method adjusting by randomization strata, separately for each week. Results from multiply imputed data sets were combined using Rubin's rules to obtain treatment difference, 95% CI and p-value.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

22.5

Confidence interval

level

95%

sides

2-sided

lower limit

10.3

upper limit

34.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

41.7

Confidence interval

level

95%

sides

2-sided

lower limit

29.6

upper limit

53.9

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)

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End point title

Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)

End point description

Subjects were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. Per-protocol analysis set included all randomized subjects who received at least 1 dose of study medication and who had no major protocol violations. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	127	126	54
Units: percentage of subjects
number (not applicable)
Week 2	20.5	47.6	3.7
Week 4	34.0	63.3	20.7
Week 12	41.1	60.6	12.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0055

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

16.3

Confidence interval

level

95%

sides

2-sided

lower limit

7.4

upper limit

25.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

43.3

Confidence interval

level

95%

sides

2-sided

lower limit

33.1

upper limit

53.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1138

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

12.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

41.8

Confidence interval

level

95%

sides

2-sided

lower limit

26.2

upper limit

57.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

28.7

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

42.1

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

47.8

Confidence interval

level

95%

sides

2-sided

lower limit

34.6

upper limit

61.1

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set

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End point title

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set

End point description

PSAAD is a daily subject reported symptom electronic diary. Subjects 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 [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Subject 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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	137	138	68
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-1.5 (-1.7 to -1.2)	-2.1 (-2.3 to -1.8)	-0.5 (-0.8 to -0.1)
Change at Week 4	-1.8 (-2.1 to -1.5)	-3.0 (-3.2 to -2.7)	-0.7 (-1.1 to -0.3)
Change at Week 8	-2.2 (-2.5 to -1.8)	-3.1 (-3.5 to -2.8)	-1.2 (-1.7 to -0.7)
Change at Week 12	-2.2 (-2.6 to -1.9)	-3.2 (-3.6 to -2.8)	-1.1 (-1.7 to -0.6)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Change at Week 2: Mixed model repeated measure (MMRM) contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

205

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in least squares (LS) mean

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Change at Week 2: MMRM contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1.2

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Change at Week 4: MMRM contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

205

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-1.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Change at Week 8: MMRM contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

205

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0035

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

-0.3

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-1.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Change at Week 12: MMRM contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

205

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

-0.4

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-1.4

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set

Top of page

End point title

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set

End point description

PSAAD is a daily subject reported symptom electronic diary. subjects 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 [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Subject 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. Per-protocol analysis set included all randomized subjects who received at least 1 dose of study medication and who had no major protocol violations. Here, N=subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	115	117	50
Units: units on a scale
least squares mean (confidence interval 95%)	-2.4 (-2.8 to -2.1)	-3.4 (-3.8 to -3.0)	-1.1 (-1.7 to -0.5)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

MMRM contained fixed factors of treatment, week, treatment by week interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

165

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1.6

Secondary: Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus

Top of page

End point title

Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus

End point description

Subjects were asked to assess their worst itching/pruritus due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst itch imaginable), where higher scores indicated greater severity. 95% CI was based on the Brookmeyer and Crowley method. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point. 99999 signifies that upper limit was not evaluable since very less events were observed.

End point type

Secondary

End point timeframe

Baseline up to Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	73	106	23
Units: days
median (confidence interval 95%)	84.0 (56.0 to 99999)	14.0 (11.0 to 29.0)	92.0 (85.0 to 99999)

Placebo Vs PF-04965842 100 mg

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0071 ^[4]

Method

Logrank

Confidence interval

Notes
[4] - P-value was controlled by randomization strata.

Placebo Vs PF-04965842 200 mg

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[5]

Method

Logrank

Confidence interval

Notes
[5] - P-value was controlled by randomization strata.

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8

End point description

EASI evaluates severity of subjects AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % BSA affected. Severity of clinical signs of AD [erythema (E), induration/papulation (I), excoriation (Ex) and lichenification (L) scored separately for each of 4 body regions (head and neck (h), upper limbs (u), trunk [including axillae and groin)] (t) and lower limbs [including buttocks] (l)) 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-<10%), 2(10-<30%), 3(30-<50%), 4(50-<70%), 5(70-<90%) and 6(90-100%). Total EASI score ranged from 0.0-72.0, higher scores = greater severity of AD. FAS=all randomized subjects who received at least 1 dose of study medication. Here, N=subjects evaluable for this end point and “Number Analyzed” (n) signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	155	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154,77)	10.3	24.0	3.9
Week 4 (n=152, 152, 76)	27.6	47.4	14.5
Week 8 (n=154, 154, 75)	38.3	57.8	13.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0869 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

13.3

Notes
[6] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

28.6

Notes
[7] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0259 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

23.6

Notes
[8] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

21.7

upper limit

44.2

Notes
[9] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.2

upper limit

35.8

Notes
[10] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

44.6

Confidence interval

level

95%

sides

2-sided

lower limit

33.6

upper limit

55.6

Notes
[11] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8

Top of page

End point title

Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8

End point description

IGA assesses severity of AD on a 5 point scale (0-4, higher scores indicate more severity), 0=clear, no inflammatory signs of AD; 1=almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2=mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3=moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4=severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp. FAS=all randomized subjects who received at least 1 dose of study medication. Here, N=subjects evaluable for this end point and n=subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	155	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	3.9	9.7	0
Week 4 (152, 152, 76)	10.5	27.0	5.3
Week 8 (153, 154, 75)	20.3	35.7	6.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0802 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

8.5

Notes
[12] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0045 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

15.7

Notes
[13] - P-value was adjusted by randomization strata (baseline disease severity and age category)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1888 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

12.4

Notes
[14] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[15]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

21.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

30.5

Notes
[15] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0071 ^[16]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.8

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

22.4

Notes
[16] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

29.3

Confidence interval

level

95%

sides

2-sided

lower limit

19.8

upper limit

38.7

Notes
[17] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12

End point description

IGA assesses severity of AD on a 5 point scale (0-4, higher scores indicate more severity), 0=clear, no inflammatory signs of AD; 1=almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2=mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3=moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4=severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp. FAS=all randomized subjects who received at least 1 dose of study medication. Here, n=subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	0	0	0
Week 4 (n=152, 152, 76)	0	6.6	0
Week 8 (n=153, 154, 75)	4.6	11.7	0
Week 12 (n=156, 153, 76)	7.1	13.1	0

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

3.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0234 ^[18]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

11.7

Notes
[18] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0592 ^[19]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

9.5

Notes
[19] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022 ^[20]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.5

upper limit

17.9

Notes
[20] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

12.3

Notes
[21] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

6.7

upper limit

19.4

Notes
[22] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

End point description

EASI evaluates severity of subjects AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % BSA affected. Severity of clinical signs of AD [erythema (E), induration/papulation (I), excoriation (Ex) and lichenification (L) scored separately for each of 4 body regions (head and neck (h), upper limbs (u), trunk [including axillae and groin)] (t) and lower limbs [including buttocks] (l)) 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-<10%), 2(10-<30%), 3(30-<50%), 4(50-<70%), 5(70-<90%) and 6(90-100%). Total EASI score ranged from 0.0-72.0, higher scores = greater severity of AD. FAS=randomized subjects who received at least 1 dose of study medication. Here, n=subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	34.2	55.2	10.4
Week 4 (n=152, 152, 76)	54.6	73.7	21.1
Week 8 (n=154, 154, 75)	57.8	76.6	24.0
Week 12 (n=156, 153, 76)	57.7	75.8	22.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[23]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.9

upper limit

34.1

Notes
[23] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[24]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

45.1

Confidence interval

level

95%

sides

2-sided

lower limit

34.7

upper limit

55.5

Notes
[24] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[25]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

33.5

Confidence interval

level

95%

sides

2-sided

lower limit

21.6

upper limit

45.4

Notes
[25] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[26]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

52.7

Confidence interval

level

95%

sides

2-sided

lower limit

41.2

upper limit

64.2

Notes
[26] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[27]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

34.1

Confidence interval

level

95%

sides

2-sided

lower limit

21.9

upper limit

46.3

Notes
[27] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

52.9

Confidence interval

level

95%

sides

2-sided

lower limit

41.3

upper limit

64.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[28]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

35.3

Confidence interval

level

95%

sides

2-sided

lower limit

23.3

upper limit

47.4

Notes
[28] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[29]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

53.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[29] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12

End point description

EASI evaluates severity of subjects AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % BSA affected. Severity of clinical signs of AD [erythema (E), induration/papulation (I), excoriation (Ex) and lichenification (L) scored separately for each of 4 body regions (head and neck (h), upper limbs (u), trunk [including axillae and groin)] (t) and lower limbs [including buttocks] (l)) 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-<10%), 2(10-<30%), 3(30-<50%), 4(50-<70%), 5(70-<90%) and 6(90-100%). Total EASI score ranged from 0.0-72.0, higher scores = greater severity of AD. FAS=all randomized subjects who received at least 1 dose of study medication. Here, n=subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	1.9	5.2	1.3
Week 4 (n=152, 152, 76)	7.9	24.3	3.9
Week 8 (n=154, 154, 75)	14.3	33.1	5.3
Week 12 (n=156, 153, 76)	18.6	38.6	5.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7285 ^[30]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

5.2

Notes
[30] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1448 ^[31]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

9.2

Notes
[31] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2576 ^[32]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

10.5

Notes
[32] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[33]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

28.9

Notes
[33] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0423

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

16.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[34]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

18.7

upper limit

37.2

Notes
[34] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0066 ^[35]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.3

Confidence interval

level

95%

sides

2-sided

lower limit

5.4

upper limit

21.2

Notes
[35] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[36]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

33.4

Confidence interval

level

95%

sides

2-sided

lower limit

24.3

upper limit

42.5

Notes
[36] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12

End point description

EASI evaluates severity of subjects AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % BSA affected. Severity of clinical signs of AD [erythema (E), induration/papulation (I), excoriation (Ex) and lichenification (L) scored separately for each of 4 body regions (head and neck (h), upper limbs (u), trunk [including axillae and groin)] (t) and lower limbs [including buttocks] (l)) 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-<10%), 2(10-<30%), 3(30-<50%), 4(50-<70%), 5(70-<90%) and 6(90-100%). Total EASI score ranged from 0.0-72.0, higher scores = greater severity of AD. FAS=all randomized subjects who received at least 1 dose of study medication. Here, n=subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	0	0	0
Week 4 (n=152, 152, 76)	0	6.6	0
Week 8 (n=154, 154, 75)	4.5	11.7	0
Week 12 (n=156, 153, 76)	6.4	13.1	0

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

3.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0234 ^[37]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

11.7

Notes
[37] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0604 ^[38]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

9.5

Notes
[38] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022 ^[39]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

5.5

upper limit

17.9

Notes
[39] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0255 ^[40]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

11.6

Notes
[40] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[41]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

6.7

upper limit

19.4

Notes
[41] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-9.8 (-11.3 to -8.4)	-14.7 (-16.1 to -13.3)	-4.1 (-6.1 to -2.1)
Change at Week 4	-14.7 (-16.3 to -13.1)	-19.6 (-21.2 to -17.9)	-6.8 (-9.2 to -4.5)
Change at Week 8	-16.3 (-18.1 to -14.6)	-21.3 (-23.0 to -19.5)	-7.8 (-10.3 to -5.3)
Change at Week 12	-16.6 (-18.4 to -14.7)	-22.3 (-24.1 to -20.4)	-8.2 (-10.9 to -5.5)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.2

upper limit

-3.3

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-10.6

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

-8.1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

-5

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-12.7

Confidence interval

level

95%

sides

2-sided

lower limit

-15.6

upper limit

-9.9

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-11.6

upper limit

-5.5

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.5

upper limit

-10.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-8.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.6

upper limit

-5.1

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-14

Confidence interval

level

95%

sides

2-sided

lower limit

-17.3

upper limit

-10.8

Secondary: Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12

End point description

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of subject’s hand with fingers in a closed position) fitting in the 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=10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. % BSA for a body region was calculated as=total number of handprints in a body region*% surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0-100%, with higher values representing greater severity of AD. FAS=all randomized subjects who received at least 1 dose of study medication.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: Percentage BSA
least squares mean (confidence interval 95%)
Change at Week 2	-11.8 (-14.3 to -9.4)	-18.8 (-21.3 to -16.4)	-4.0 (-7.6 to -0.5)
Change at Week 4	-20.2 (-23.0 to -17.4)	-27.0 (-29.8 to -24.2)	-8.5 (-12.5 to -4.5)
Change at Week 8	-23.2 (-26.3 to -20.2)	-31.5 (-34.6 to -28.5)	-8.9 (-13.3 to -4.5)
Change at Week 12	-25.1 (-28.3 to -22.0)	-33.4 (-36.6 to -30.3)	-11.4 (-16.0 to -6.8)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

-3.5

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-14.8

Confidence interval

level

95%

sides

2-sided

lower limit

-19

upper limit

-10.5

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-16.6

upper limit

-6.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-18.5

Confidence interval

level

95%

sides

2-sided

lower limit

-23.4

upper limit

-13.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-19.7

upper limit

-9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-22.6

Confidence interval

level

95%

sides

2-sided

lower limit

-28

upper limit

-17.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-13.8

Confidence interval

level

95%

sides

2-sided

lower limit

-19.3

upper limit

-8.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-22

Confidence interval

level

95%

sides

2-sided

lower limit

-27.6

upper limit

-16.5

Secondary: Percentage of Subjects With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12

End point description

4 body regions were evaluated: head and neck (h), upper limbs (u), trunk (including axillae and groin) (t) and lower limbs (including buttocks) (l). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of subject’s hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for h, 20 for u, 30 for t and 40 for l. Surface area of body region equivalent to 1 handprint: 1 handprint:10%=h, 5%=u, 3.33%=t and 2.5%=l. % BSA for a body region was calculated as=total number of handprints in a body region*% surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0-100%, with higher values representing greater severity of AD. FAS=all randomized subjects who received at least 1 dose of study medication. Here, n=subjects evaluable at the specified time points.

End point type

Secondary

End point timeframe

Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	156	154	77
Units: percentage of subjects
number (not applicable)
Week 2 (n=155, 154, 77)	2.6	5.2	1.3
Week 4 (n=152, 152, 76)	8.6	27.6	3.9
Week 8 (n=154, 154, 75)	16.2	33.1	6.7
Week 12 (n=156, 153, 76)	21.2	38.6	5.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.521 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

Notes
[42] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1416 ^[43]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

9.3

Notes
[43] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2002 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

11.2

Notes
[44] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

23.6

Confidence interval

level

95%

sides

2-sided

lower limit

15.1

upper limit

32.2

Notes
[45] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0434 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

17.9

Notes
[46] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[47]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

26.6

Confidence interval

level

95%

sides

2-sided

lower limit

17.1

upper limit

36.2

Notes
[47] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

233

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019 ^[48]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

15.8

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

Notes
[48] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[49]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

33.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

42.7

Notes
[49] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

End point description

SCORAD:scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region-head and neck 9%, upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was added to give 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; scores were summed to give B(0-18). C: pruritus and sleep, each of these 2 were scored by subject/caregiver using visual analogue scale (VAS) where “0”=no itch/no sleeplessness; “10”=the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C;range=0-103;higher values=worse outcome. FAS analysis set."N”=subjects evaluable for this end point; “n”=subjects evaluable at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	148	150	75
Units: percentage of subjects
number (not applicable)
Week 2 (n=148, 150, 75)	14.9	34.0	4.0
Week 4 (n=145, 148, 70)	34.5	50.7	12.9
Week 8 (n=146, 148, 72)	36.3	54.1	12.5
Week 12 (n=145, 146, 73)	36.6	56.8	16.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0151 ^[50]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

18.3

Notes
[50] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[51]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[51] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[52]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

21.2

Confidence interval

level

95%

sides

2-sided

lower limit

10.2

upper limit

32.3

Notes
[52] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[53]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

37.9

Confidence interval

level

95%

sides

2-sided

lower limit

26.6

upper limit

49.3

Notes
[53] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003 ^[54]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

23.5

Confidence interval

level

95%

sides

2-sided

lower limit

12.6

upper limit

34.3

Notes
[54] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[55]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

41.7

Confidence interval

level

95%

sides

2-sided

lower limit

30.7

upper limit

52.7

Notes
[55] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0026 ^[56]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

19.6

Confidence interval

level

95%

sides

2-sided

lower limit

8.1

upper limit

31.1

Notes
[56] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[57]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

28.3

upper limit

51.7

Notes
[57] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	148	150	75
Units: percentage of subjects
number (not applicable)
Week 2 (n=148, 150, 75)	1.4	6.0	0
Week 4 (n=145, 148, 70)	2.8	18.2	2.9
Week 8 (n=146, 148, 72)	12.3	23.6	1.4
Week 12 (n=145, 146, 73)	12.4	30.8	4.1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3151 ^[58]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

5.6

Notes
[58] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0292 ^[59]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

11.3

Notes
[59] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9402 ^[60]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

5.5

Notes
[60] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019 ^[61]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

15.3

Confidence interval

level

95%

sides

2-sided

lower limit

7.3

upper limit

23.2

Notes
[61] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0078 ^[62]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

17.4

Notes
[62] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[63]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

22.2

Confidence interval

level

95%

sides

2-sided

lower limit

14.2

upper limit

30.1

Notes
[63] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0528 ^[64]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

8.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

15.3

Notes
[64] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[65]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

26.4

Confidence interval

level

95%

sides

2-sided

lower limit

17.6

upper limit

35.3

Notes
[65] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12

End point description

SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9% upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was 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. The severity scores added to give B (0-18). C: pruritus and sleep loss, each of these 2 were scored by subject/caregiver using VAS where “0” = no itch or no sleeplessness and “10” = the worst imaginable itch or sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C; range=0-103; higher values=worse outcome. FAS analysis set."N”=subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	154	153	77
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-2.1 (-2.4 to -1.7)	-3.1 (-3.5 to -2.8)	-0.8 (-1.3 to -0.3)
Change at Week 4	-2.5 (-2.9 to -2.1)	-3.7 (-4.1 to -3.3)	-1.0 (-1.5 to -0.4)
Change at Week 8	-2.8 (-3.2 to -2.4)	-3.8 (-4.2 to -3.4)	-1.3 (-1.9 to -0.7)
Change at Week 12	-2.9 (-3.4 to -2.5)	-3.7 (-4.2 to -3.3)	-1.6 (-2.2 to -1.0)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-2

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

-0.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

-1.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

-1.4

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12

End point description

SCORAD: scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9% upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was 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. The severity scores added to give B (0-18). C: pruritus and sleep loss, each of these 2 were scored by subject/caregiver using VAS where “0” = no itch or no sleeplessness and “10” = the worst imaginable itch or sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C; range=0-103; higher values=worse outcome. FAS analysis set."N”=subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	150	151	75
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-16.4 (-18.7 to -14.2)	-24.4 (-26.7 to -22.2)	-5.5 (-8.7 to -2.4)
Change at Week 4	-23.1 (-25.8 to -20.4)	-32.6 (-35.3 to -29.9)	-10.5 (-14.4 to -6.7)
Change at Week 8	-26.0 (-29.1 to -23.0)	-33.7 (-36.7 to -30.7)	-11.7 (-16.0 to -7.4)
Change at Week 12	-27.0 (-30.2 to -23.7)	-35.5 (-38.7 to -32.3)	-13.6 (-18.3 to -9.0)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-10.9

Confidence interval

level

95%

sides

2-sided

lower limit

-14.8

upper limit

-7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-18.9

Confidence interval

level

95%

sides

2-sided

lower limit

-22.7

upper limit

-15.1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-12.6

Confidence interval

level

95%

sides

2-sided

lower limit

-17.3

upper limit

-7.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-22.1

Confidence interval

level

95%

sides

2-sided

lower limit

-26.8

upper limit

-17.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-14.3

Confidence interval

level

95%

sides

2-sided

lower limit

-19.5

upper limit

-9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-22

Confidence interval

level

95%

sides

2-sided

lower limit

-27.2

upper limit

-16.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

225

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-13.3

Confidence interval

level

95%

sides

2-sided

lower limit

-19

upper limit

-7.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-21.9

Confidence interval

level

95%

sides

2-sided

lower limit

-27.5

upper limit

-16.3

Secondary: Percentage of Subjects Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12

End point description

PSAAD is a daily subject reported symptom electronic diary. Subjects 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 [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Subject 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). Total PSAAD score=arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point and "Number Analyzed” signifies number of subjects evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	135	136	67
Units: percentage of subjects
number (not applicable)
Week 2 (n=133, 135, 67)	51.1	68.9	28.4
Week 4 (n=134, 132, 67)	62.7	77.3	44.8
Week 8 (n=133, 136, 67)	60.9	69.1	44.8
Week 12 (n=132, 128, 66)	61.4	70.3	40.9

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0028 ^[66]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

22.3

Confidence interval

level

95%

sides

2-sided

lower limit

8.7

upper limit

35.9

Notes
[66] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[67]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

40.1

Confidence interval

level

95%

sides

2-sided

lower limit

27.1

upper limit

53.2

Notes
[67] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0217 ^[68]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

17.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

31.4

Notes
[68] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[69]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

32.2

Confidence interval

level

95%

sides

2-sided

lower limit

18.5

upper limit

45.9

Notes
[69] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0363 ^[70]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

Notes
[70] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011 ^[71]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

23.7

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

37.7

Notes
[71] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

202

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[72]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.1

Confidence interval

level

95%

sides

2-sided

lower limit

5.8

upper limit

34.5

Notes
[72] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[73]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

29.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

43.3

Notes
[73] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12

End point description

DLQI is a 10-item questionnaire that measures the impact of skin disease on subject's (aged above 17 years) quality of life over the last week. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions 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 subjects. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	121	119	60
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-5.9 (-6.9 to -5.0)	-7.6 (-8.6 to -6.7)	-2.1 (-3.5 to -0.8)
Change at Week 4	-6.8 (-7.8 to -5.9)	-9.6 (-10.6 to -8.7)	-3.5 (-4.9 to -2.1)
Change at Week 8	-6.8 (-7.9 to -5.6)	-9.3 (-10.5 to -8.2)	-4.0 (-5.6 to -2.3)
Change at Week 12	-7.0 (-8.1 to -5.8)	-9.1 (-10.3 to -8.0)	-4.2 (-5.9 to -2.5)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

-2.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-3.9

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

-1.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-6.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

-4.5

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0075

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

-0.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

-3.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0072

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

-0.8

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

-2.9

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12

End point 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 ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of children. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	32	32	16
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-4.5 (-5.8 to -3.2)	-5.8 (-7.1 to -4.5)	-3.3 (-5.1 to -1.4)
Change at Week 4	-5.3 (-6.7 to -4.0)	-8.2 (-9.5 to -6.8)	-1.8 (-3.8 to 0.2)
Change at Week 8	-5.2 (-6.9 to -3.6)	-7.5 (-9.2 to -5.9)	-3.1 (-5.6 to -0.6)
Change at Week 12	-6.4 (-7.9 to -5.0)	-7.5 (-8.9 to -6.0)	-3.9 (-6.1 to -1.7)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.275

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.028

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

-0.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0051

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

-1.1

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

-4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1706

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

0.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0048

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

-1.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0629

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

0.1

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

-0.9

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	120	119	59
Units: percentage of subjects
number (not applicable)
Week 2 (n=120, 119, 59)	10.0	23.5	3.4
Week 4 (n=118, 117, 59)	15.3	32.5	8.5
Week 8 (n=118, 119, 57)	17.8	35.3	8.8
Week 12 (n=119, 119, 58)	20.2	31.9	12.1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1238 ^[74]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

13.9

Notes
[74] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008 ^[75]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

29.2

Notes
[75] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2091 ^[76]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

16.4

Notes
[76] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005 ^[77]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.9

upper limit

Notes
[77] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1161 ^[78]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

19.1

Notes
[78] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[79]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

26.5

Confidence interval

level

95%

sides

2-sided

lower limit

15.3

upper limit

37.7

Notes
[79] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1837 ^[80]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

19.1

Notes
[80] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0046 ^[81]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

19.8

Confidence interval

level

95%

sides

2-sided

lower limit

8.1

upper limit

31.6

Notes
[81] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With Baseline Children’s Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Baseline Children’s Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	31	31	16
Units: percentage of subjects
number (not applicable)
Week 2 (n=31, 31, 16)	3.2	0	0
Week 4 (n=30, 31, 15)	13.3	9.7	0
Week 8 (n=31, 31, 14)	12.9	12.9	7.1
Week 12 (n=31, 31, 15)	19.4	9.7	0

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4795 ^[82]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.3

upper limit

16.6

Notes
[82] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

12.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1452 ^[83]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

13.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

30.3

Notes
[83] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2232 ^[84]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

25.4

Notes
[84] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5707 ^[85]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-13.7

upper limit

25.4

Notes
[85] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5777 ^[86]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-13.6

upper limit

25.1

Notes
[86] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0744 ^[87]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

19.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

37.5

Notes
[87] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2232 ^[88]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

25.4

Notes
[88] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	117	117	56
Units: percentage of subjects
number (not applicable)
Week 2 (n=117, 117, 56)	67.5	71.8	35.7
Week 4 (n=115, 115, 56)	72.2	85.2	51.8
Week 8 (n=116, 117, 54)	64.7	82.1	48.1
Week 12 (n=116, 117, 55)	67.2	72.6	43.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[89]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

31.6

Confidence interval

level

95%

sides

2-sided

lower limit

17.2

upper limit

Notes
[89] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[90]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

35.7

Confidence interval

level

95%

sides

2-sided

lower limit

21.5

upper limit

49.9

Notes
[90] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[91]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.4

Confidence interval

level

95%

sides

2-sided

lower limit

5.2

upper limit

35.6

Notes
[91] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[92]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

33.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

47.7

Notes
[92] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0421 ^[93]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

16.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

32.4

Notes
[93] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[94]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

33.8

Confidence interval

level

95%

sides

2-sided

lower limit

18.9

upper limit

48.8

Notes
[94] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0035 ^[95]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

23.5

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

38.8

Notes
[95] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[96]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

28.8

Confidence interval

level

95%

sides

2-sided

lower limit

13.8

upper limit

43.9

Notes
[96] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	30	31	16
Units: percentage of subjects
number (not applicable)
Week 2 (n=30, 31, 16)	73.3	74.2	56.3
Week 4 (n=29, 31, 15)	69.0	83.9	40.0
Week 8 (n=30, 31, 14)	66.7	77.4	35.7
Week 12 (n=30, 31, 15)	73.3	83.9	53.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2497 ^[97]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

17.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

43.2

Notes
[97] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2371

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

17.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

43.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0697 ^[98]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

28.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

58.3

Notes
[98] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[99]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

43.9

Confidence interval

level

95%

sides

2-sided

lower limit

16.2

upper limit

71.7

Notes
[99] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0583 ^[100]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

59.9

Notes
[100] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085 ^[101]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

41.2

Confidence interval

level

95%

sides

2-sided

lower limit

13.2

upper limit

69.1

Notes
[101] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1948 ^[102]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

19.3

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

48.5

Notes
[102] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0296 ^[103]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

30.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

58.5

Notes
[103] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), 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-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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	152	152	76
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-0.7 (-1.0 to -0.3)	-1.3 (-1.6 to -0.9)	-0.2 (-0.7 to 0.3)
Change at Week 4	-1.1 (-1.6 to -0.7)	-1.7 (-2.1 to -1.3)	0.1 (-0.5 to 0.7)
Change at Week 8	-1.0 (-1.4 to -0.6)	-2.0 (-2.4 to -1.6)	-0.3 (-0.9 to 0.3)
Change at Week 12	-1.4 (-1.8 to -0.9)	-1.8 (-2.2 to -1.4)	-0.2 (-0.8 to 0.4)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1718

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

-0.4

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-0.6

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

-1.1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0476

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

-1

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0028

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

-0.4

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

-0.9

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), 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-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). 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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	152	152	76
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-1.1 (-1.5 to -0.7)	-1.7 (-2.0 to -1.3)	-0.9 (-1.5 to -0.4)
Change at Week 4	-1.4 (-1.9 to -1.0)	-2.2 (-2.6 to -1.8)	-1.0 (-1.6 to -0.4)
Change at Week 8	-1.5 (-1.9 to -1.0)	-2.3 (-2.7 to -1.8)	-1.0 (-1.7 to -0.4)
Change at Week 12	-1.6 (-2.0 to -1.1)	-2.1 (-2.5 to -1.6)	-1.0 (-1.7 to -0.4)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6134

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.5

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0422

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.205

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.3

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

-0.5

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2657

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.3

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-0.5

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1675

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

-0.3

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), 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-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). 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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point and "Number Analyzed” signifies number of subjects evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	33	34	18
Units: percentage of subjects
number (not applicable)
Week 2 (n=33, 34, 18)	48.5	64.7	38.9
Week 4 (n=32, 33, 18)	50.0	54.5	55.6
Week 8 (n=33, 34, 18)	42.4	58.8	22.2
Week 12 (n=33, 33, 18)	39.4	48.5	38.9

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5539 ^[104]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

8.8

Confidence interval

level

95%

sides

2-sided

lower limit

-19.6

upper limit

37.2

Notes
[104] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0561 ^[105]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

27.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

55.1

Notes
[105] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.746 ^[106]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-33.4

upper limit

23.7

Notes
[106] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[107]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-28.3

upper limit

28.3

Notes
[107] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1474 ^[108]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

20.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

46.2

Notes
[108] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0123 ^[109]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

37.3

Confidence interval

level

95%

sides

2-sided

lower limit

12.1

upper limit

62.5

Notes
[109] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.976 ^[110]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-28.5

upper limit

27.6

Notes
[110] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5965 ^[111]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-20.4

upper limit

36.1

Notes
[111] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	22	20	9
Units: percentage of subjects
number (not applicable)
Week 2 (n=22, 20, 9)	45.5	60.0	22.2
Week 4 (n=22, 19, 9)	68.2	68.4	55.6
Week 8 (n=21, 20, 9)	57.1	70.0	66.7
Week 12 (n=22, 20, 9)	50.0	75.0	33.3

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2278 ^[112]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

Notes
[112] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0996 ^[113]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

35.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

72.4

Notes
[113] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4449 ^[114]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

14.5

Confidence interval

level

95%

sides

2-sided

lower limit

-21.6

upper limit

50.6

Notes
[114] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4139 ^[115]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

16.9

Confidence interval

level

95%

sides

2-sided

lower limit

-21.6

upper limit

55.5

Notes
[115] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.729 ^[116]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-6.7

Confidence interval

level

95%

sides

2-sided

lower limit

-40.7

upper limit

27.4

Notes
[116] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6585 ^[117]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-27.3

upper limit

44.6

Notes
[117] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3638 ^[118]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

18.2

Confidence interval

level

95%

sides

2-sided

lower limit

-18.7

upper limit

55.1

Notes
[118] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055 ^[119]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

40.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

78.5

Notes
[119] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), 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-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). 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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point and "Number Analyzed” signifies number of subjects evaluable at the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	16	13	8
Units: percentage of subjects
number (not applicable)
Week 2 (n=16, 13, 8)	56.3	46.2	75.0
Week 4 (n=16, 12, 8)	56.3	58.3	75.0
Week 8 (n=16, 13, 8)	56.3	53.8	75.0
Week 12 (n=16, 13, 8)	43.8	46.2	37.5

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4036 ^[120]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-18.8

Confidence interval

level

95%

sides

2-sided

lower limit

-58.4

upper limit

20.9

Notes
[120] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.158 ^[121]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-35.3

Confidence interval

level

95%

sides

2-sided

lower limit

-75.9

upper limit

5.3

Notes
[121] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.514 ^[122]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-14.2

Confidence interval

level

95%

sides

2-sided

lower limit

-53.5

upper limit

25.1

Notes
[122] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4149 ^[123]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-19.8

Confidence interval

level

95%

sides

2-sided

lower limit

-63.3

upper limit

23.7

Notes
[123] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4036 ^[124]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-18.8

Confidence interval

level

95%

sides

2-sided

lower limit

-58.4

upper limit

20.9

Notes
[124] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2092 ^[125]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-30.7

Confidence interval

level

95%

sides

2-sided

lower limit

-70.9

upper limit

9.6

Notes
[125] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5982 ^[126]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

11.9

Confidence interval

level

95%

sides

2-sided

lower limit

-29.1

upper limit

Notes
[126] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8647 ^[127]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-36.3

upper limit

44.7

Notes
[127] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), 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-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. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, "Number of Subjects Analyzed” subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	5	8	3
Units: percentage of subjects
number (not applicable)
Week 2	20.0	75.0	100.0
Week 4	60.0	75.0	66.7
Week 8	40.0	75.0	66.7
Week 12	40.0	75.0	66.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0546 ^[128]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-78.6

Confidence interval

level

95%

sides

2-sided

lower limit

-117.5

upper limit

-39.6

Notes
[128] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3573 ^[129]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-27.9

Confidence interval

level

95%

sides

2-sided

lower limit

-62.5

upper limit

6.7

Notes
[129] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9219 ^[130]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-55.6

upper limit

48.5

Notes
[130] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3173 ^[131]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

63.6

Notes
[131] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5408 ^[132]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-25

Confidence interval

level

95%

sides

2-sided

lower limit

-77

upper limit

Notes
[132] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3173 ^[133]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

63.6

Notes
[133] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v PF-04965842 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5408 ^[134]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

-25

Confidence interval

level

95%

sides

2-sided

lower limit

-77

upper limit

Notes
[134] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3173 ^[135]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

63.6

Notes
[135] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12

End point description

POEM is a 7-item subject reported outcome measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	153	153	77
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-4.6 (-5.5 to -3.7)	-8.1 (-9.0 to -7.2)	-1.8 (-3.1 to -0.5)
Change at Week 4	-6.2 (-7.2 to -5.1)	-10.8 (-11.8 to -9.8)	-2.4 (-3.9 to -0.9)
Change at Week 8	-6.1 (-7.3 to -4.9)	-10.6 (-11.8 to -9.5)	-3.4 (-5.1 to -1.7)
Change at Week 12	-6.8 (-8.0 to -5.6)	-10.6 (-11.8 to -9.4)	-3.7 (-5.5 to -1.9)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

-1.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

-4.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

-2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-8.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

-6.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0096

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

-0.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

-5.2

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0049

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-0.9

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

-4.7

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

End point description

Subject responded to “Overall, how would you describe your Atopic Dermatitis right now?” on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	154	153	77
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-0.6 (-0.8 to -0.5)	-1.1 (-1.2 to -0.9)	-0.3 (-0.5 to -0.1)
Change at Week 4	-0.8 (-1.0 to -0.7)	-1.3 (-1.5 to -1.2)	-0.4 (-0.6 to -0.1)
Change at Week 8	-1.0 (-1.1 to -0.8)	-1.4 (-1.6 to -1.2)	-0.5 (-0.7 to -0.2)
Change at Week 12	-1.0 (-1.2 to -0.9)	-1.5 (-1.7 to -1.3)	-0.5 (-0.8 to -0.3)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

-0.1

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.2

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.7

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.6

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.2

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

230

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

-0.6

Secondary: Percentage of Subjects Achieving 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Top of page

End point title

Percentage of Subjects Achieving 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

End point description

Subject responded to “Overall, how would you describe your Atopic Dermatitis right now?” on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, "Number of Subjects Analyzed” signifies subjects evaluable for this end point and “Number Analyzed” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	153	151	75
Units: percentage of subjects
number (not applicable)
Week 2 (n=153, 151, 75)	7.2	19.2	1.3
Week 4 (n=151, 149, 74)	14.6	31.5	5.4
Week 8 (n=151, 151, 71)	17.2	34.4	8.5
Week 12 (n=152, 150, 73)	21.1	36.0	6.8

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0575 ^[136]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

11.7

Notes
[136] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[137]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

18.1

Confidence interval

level

95%

sides

2-sided

lower limit

10.7

upper limit

25.5

Notes
[137] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0411 ^[138]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

9.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

17.1

Notes
[138] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[139]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

26.2

Confidence interval

level

95%

sides

2-sided

lower limit

16.9

upper limit

35.5

Notes
[139] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0781 ^[140]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

Notes
[140] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[141]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

26.2

Confidence interval

level

95%

sides

2-sided

lower limit

16.2

upper limit

36.3

Notes
[141] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

228

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0075 ^[142]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

14.2

Confidence interval

level

95%

sides

2-sided

lower limit

5.3

upper limit

23.2

Notes
[142] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

226

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[143]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

29.3

Confidence interval

level

95%

sides

2-sided

lower limit

19.6

upper limit

38.9

Notes
[143] - P-value was adjusted by randomization strata (baseline disease severity and age category).

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L): Index Value at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L): Index Value at Week 2, 4, 8 and 12

End point description

EQ-5D-5L: standardized participant (aged >17 years) completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded “no problems” for each 5 dimensions, then health state was coded as “11111” with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state. FAS analysis set. “N”=subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	121	119	60
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	0.049 (0.030 to 0.068)	0.084 (0.065 to 0.103)	0.016 (-0.011 to 0.043)
Change at Week 4	0.062 (0.041 to 0.084)	0.092 (0.070 to 0.114)	0.037 (0.007 to 0.067)
Change at Week 8	0.053 (0.029 to 0.077)	0.097 (0.074 to 0.121)	0.005 (-0.029 to 0.039)
Change at Week 12	0.058 (0.034 to 0.083)	0.078 (0.054 to 0.103)	0.014 (-0.021 to 0.050)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0453

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.034

Confidence interval

level

95%

sides

2-sided

lower limit

0.001

upper limit

0.066

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.068

Confidence interval

level

95%

sides

2-sided

lower limit

0.036

upper limit

0.101

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1821

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.025

Confidence interval

level

95%

sides

2-sided

lower limit

-0.012

upper limit

0.062

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0038

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.055

Confidence interval

level

95%

sides

2-sided

lower limit

0.018

upper limit

0.092

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0241

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.048

Confidence interval

level

95%

sides

2-sided

lower limit

0.006

upper limit

0.09

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.093

Confidence interval

level

95%

sides

2-sided

lower limit

0.051

upper limit

0.134

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0461

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.044

Confidence interval

level

95%

sides

2-sided

lower limit

0.001

upper limit

0.087

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0037

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.064

Confidence interval

level

95%

sides

2-sided

lower limit

0.021

upper limit

0.107

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)- Visual Analogue Scale Score at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)- Visual Analogue Scale Score at Week 2, 4, 8 and 12

End point description

EQ-5D-5L is a standardized subject completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a subject’s (aged above 17 years) rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	121	119	60
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	5.586 (3.203 to 7.969)	9.697 (7.294 to 12.100)	1.038 (-2.361 to 4.437)
Change at Week 4	6.207 (3.473 to 8.940)	11.931 (9.174 to 14.688)	1.846 (-2.005 to 5.696)
Change at Week 8	6.982 (3.847 to 10.117)	10.740 (7.642 to 13.838)	0.937 (-3.528 to 5.402)
Change at Week 12	8.604 (5.509 to 11.699)	10.409 (7.328 to 13.489)	1.035 (-3.451 to 5.520)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0319

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

4.548

Confidence interval

level

95%

sides

2-sided

lower limit

0.397

upper limit

8.7

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

8.659

Confidence interval

level

95%

sides

2-sided

lower limit

4.496

upper limit

12.822

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0702

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

4.361

Confidence interval

level

95%

sides

2-sided

lower limit

-0.362

upper limit

9.084

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

10.085

Confidence interval

level

95%

sides

2-sided

lower limit

5.349

upper limit

14.821

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

6.045

Confidence interval

level

95%

sides

2-sided

lower limit

0.589

upper limit

11.501

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

9.803

Confidence interval

level

95%

sides

2-sided

lower limit

4.368

upper limit

15.237

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0067

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

7.569

Confidence interval

level

95%

sides

2-sided

lower limit

2.119

upper limit

13.019

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

9.374

Confidence interval

level

95%

sides

2-sided

lower limit

3.933

upper limit

14.815

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Index Value at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Index Value at Week 2, 4, 8 and 12

End point description

EQ-5D-Y: standardized subject (aged 12-17 years) completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded “no problems” for each 5 dimensions, then health state was coded as “11111” with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. UK value sets (with all possible health states) was used for adolescents in the study, range from 1 to -0.594. Higher (positive) scores = better health state. FAS analysis set. “N”=subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	31	32	16
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	0.115 (0.039 to 0.191)	0.209 (0.134 to 0.284)	0.119 (0.009 to 0.228)
Change at Week 4	0.168 (0.071 to 0.265)	0.278 (0.183 to 0.374)	-0.006 (-0.149 to 0.137)
Change at Week 8	0.122 (0.017 to 0.228)	0.198 (0.093 to 0.304)	0.118 (-0.040 to 0.275)
Change at Week 12	0.160 (0.056 to 0.265)	0.215 (0.109 to 0.322)	0.153 (-0.007 to 0.314)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9568

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

-0.004

Confidence interval

level

95%

sides

2-sided

lower limit

-0.137

upper limit

0.13

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1782

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.042

upper limit

0.223

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0491

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.174

Confidence interval

level

95%

sides

2-sided

lower limit

0.001

upper limit

0.347

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0015

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.284

Confidence interval

level

95%

sides

2-sided

lower limit

0.112

upper limit

0.456

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9638

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.004

Confidence interval

level

95%

sides

2-sided

lower limit

-0.185

upper limit

0.194

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4016

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.109

upper limit

0.27

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9429

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.007

Confidence interval

level

95%

sides

2-sided

lower limit

-0.184

upper limit

0.198

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5212

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

0.062

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.254

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Visual Analogue Scale Score at Week 2, 4, 8 and 12

Top of page

End point title

Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Visual Analogue Scale Score at Week 2, 4, 8 and 12

End point description

EQ-5D-Y is a standardized subject completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score specifically developed and validated for use by youths age 12-17 years. EQ-5D-Y consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a subject’s rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	32	32	16
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	5.515 (0.318 to 10.712)	14.933 (9.742 to 20.124)	3.384 (-4.217 to 10.985)
Change at Week 4	5.359 (-0.339 to 11.057)	15.496 (9.803 to 21.188)	-1.494 (-10.060 to 7.072)
Change at Week 8	11.828 (5.736 to 17.919)	12.510 (6.345 to 18.674)	3.156 (-6.213 to 12.524)
Change at Week 12	10.347 (5.347 to 15.347)	17.224 (12.151 to 22.297)	4.276 (-3.397 to 11.948)

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6467

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

2.131

Confidence interval

level

95%

sides

2-sided

lower limit

-7.095

upper limit

11.358

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0147

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

11.549

Confidence interval

level

95%

sides

2-sided

lower limit

2.338

upper limit

20.761

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1894

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

6.853

Confidence interval

level

95%

sides

2-sided

lower limit

-3.453

upper limit

17.159

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0015

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

16.99

Confidence interval

level

95%

sides

2-sided

lower limit

6.699

upper limit

27.281

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1267

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

8.672

Confidence interval

level

95%

sides

2-sided

lower limit

-2.518

upper limit

19.862

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1009

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

9.354

Confidence interval

level

95%

sides

2-sided

lower limit

-1.866

upper limit

20.573

Placebo Vs PF-04965842 100 mg

Statistical analysis description

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1915

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

6.071

Confidence interval

level

95%

sides

2-sided

lower limit

-3.107

upper limit

15.249

Placebo Vs PF-04965842 200 mg

Statistical analysis description

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0064

Method

Mixed models analysis

Parameter type

Difference in LS mean

Point estimate

12.948

Confidence interval

level

95%

sides

2-sided

lower limit

3.754

upper limit

22.143

Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) at Week 12

Top of page

End point title

Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) at Week 12

End point description

FACIT-F is a 13-item questionnaire. Subjects (aged above 17 years) scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Higher the subject’s response to the questions (with the exception of 2 negatively stated) greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (the best score) where higher scores indicated better overall health status (less fatigue). Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	106	108	49
Units: units on a scale
least squares mean (confidence interval 95%)	2.4 (0.8 to 3.9)	3.3 (1.7 to 4.8)	-1.3 (-3.6 to 1.0)

Placebo Vs PF-04965842 100 mg

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

155

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0102 ^[144]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

3.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

6.4

Notes
[144] - Analysis of covariance (ANCOVA) model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Placebo Vs PF-04965842 200 mg

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013 ^[145]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

7.3

Notes
[145] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Secondary: Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12

Top of page

End point title

Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12

End point description

Peds-FACIT-F is a 13-item questionnaire for adolescents of 12-17 years of age. Subjects scored each item on a 5-point scale: 0 (none of the time) to 4 (all of the time). Higher the subject’s response to the questions (with the exception of 2 negatively stated), greater was the subject’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the subject’s response). The sum of all responses resulted in the Peds-FACIT-F score for a total possible score of 0 (worse score) to 52 (the best score) where higher scores indicated better overall health status (less fatigue). Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	31	30	13
Units: units on a scale
least squares mean (confidence interval 95%)	2.2 (0.5 to 3.9)	2.1 (0.3 to 3.8)	1.2 (-1.4 to 3.9)

Placebo Vs PF-04965842 100 mg

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5241 ^[146]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

4.2

Notes
[146] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Placebo Vs PF-04965842 200 mg

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5821 ^[147]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

4.1

Notes
[147] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Secondary: Change From Baseline in Short Form-36 Version 2 (SF-36v2) Acute Summary Score at Week 12: Physical Component Summary

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End point title

Change From Baseline in Short Form-36 Version 2 (SF-36v2) Acute Summary Score at Week 12: Physical Component Summary

End point description

SF-36v2 health survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were also summarized as physical and mental component summary scores. Physical component summary: the minimum score is 0 and the maximum score is 100. Higher scores indicates a better health state. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	106	108	50
Units: units on a scale
least squares mean (confidence interval 95%)	4.3 (3.0 to 5.6)	5.2 (3.9 to 6.5)	0.5 (-1.4 to 2.4)

Placebo Vs PF-04965842 100 mg

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013 ^[148]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

6.1

Notes
[148] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Placebo Vs PF-04965842 200 mg

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[149]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

Notes
[149] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Secondary: Change From Baseline in Short Form-36v2 Acute Summary Score at Week 12: Mental Component Summary

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End point title

Change From Baseline in Short Form-36v2 Acute Summary Score at Week 12: Mental Component Summary

End point description

SF-36v2 health survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were also summarized as physical and mental component summary scores. Mental component summary: the minimum score is 0 and the maximum score is 100. Higher scores indicates a better health state. Full analysis set included all randomized subjects who received at least 1 dose of study medication. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this end point.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Number of subjects analysed	106	108	50
Units: units on a scale
least squares mean (confidence interval 95%)	1.5 (-0.1 to 3.0)	2.8 (1.3 to 4.3)	-0.2 (-2.5 to 2.0)

Placebo Vs PF-04965842 100 mg

Comparison groups

PF-04965842 100 mg v Placebo

Number of subjects included in analysis

156

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2256 ^[150]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

4.4

Notes
[150] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Placebo Vs PF-04965842 200 mg

Comparison groups

PF-04965842 200 mg v Placebo

Number of subjects included in analysis

158

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0275 ^[151]

Method

ANCOVA

Parameter type

Difference in LS mean

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

5.8

Notes
[151] - ANCOVA model was used including treatment as main effect and randomization strata (baseline disease severity and age category) and baseline value as covariates.

Secondary: Plasma Concentration Versus Time Summary of PF-04965842

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End point title

Plasma Concentration Versus Time Summary of PF-04965842 ^[152]

End point description

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ) = =1.00 nanogram per milliliter (ng/mL) to zero. Analysis set included all randomized subjects who received at least 1 dose of PF-04965842 and had pharmacokinetic measurements. Here, ‘Number Analyzed’ = subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Day 1 of Week 4: 0 hour(Pre-dose), 0.5 hours post-dose; Day 1 of Week 12: 0.5, 4 hours post-dose

Notes
[152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this endpoint

End point values	PF-04965842 100 mg	PF-04965842 200 mg
Number of subjects analysed	142	144
Units: ng/mL
arithmetic mean (standard deviation)
Week 4: 0 Hour (n=142, 144)	14.57 ± 65.044	58.16 ± 162.11
Week 4: 0.5 Hour post dose (n=116, 121)	485.3 ± 393.36	889.7 ± 786.96
Week 12: 0.5 Hour Post-dose (n=103, 106)	440.6 ± 373.81	933.9 ± 741.09
Week 12: 4 Hour Post-dose (n=119, 122)	273.1 ± 176.37	838.9 ± 544.29

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to Week 16

Adverse event reporting additional description

Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as nonserious in another subject or 1 subject may have experienced both serious and nonserious event during study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

PF-04965842 100 mg

Reporting group description

Subjects were randomized to receive a tablet of PF-04965842 100 milligram (mg) and a tablet of matching placebo orally once daily for 12 weeks. Subjects who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Reporting group title

PF-04965842 200 mg

Reporting group description

Subjects were randomized to receive PF-04965842 200 mg (2 tablets of 100 mg each) orally once daily for 12 weeks. Subjects who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Reporting group title

Placebo

Reporting group description

Subjects were randomized to receive 2 tablets of placebo matched to PF-04965842 100 mg orally once daily for 12 weeks. Subjects who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug.

Serious adverse events	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 156 (3.21%)	5 / 154 (3.25%)	3 / 77 (3.90%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 156 (0.64%)	0 / 154 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 156 (0.64%)	0 / 154 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	1 / 156 (0.64%)	0 / 154 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inflammatory bowel disease
subjects affected / exposed	0 / 156 (0.00%)	1 / 154 (0.65%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 156 (0.64%)	0 / 154 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 156 (0.00%)	2 / 154 (1.30%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	0 / 156 (0.00%)	0 / 154 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Meniscal degeneration
subjects affected / exposed	0 / 156 (0.00%)	0 / 154 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 156 (0.64%)	0 / 154 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonsillitis
subjects affected / exposed	0 / 156 (0.00%)	1 / 154 (0.65%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 156 (0.00%)	1 / 154 (0.65%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	65 / 156 (41.67%)	65 / 154 (42.21%)	26 / 77 (33.77%)
Nervous system disorders
Headache
subjects affected / exposed	12 / 156 (7.69%)	15 / 154 (9.74%)	2 / 77 (2.60%)
occurrences all number	13	18	2
Gastrointestinal disorders
Nausea
subjects affected / exposed	14 / 156 (8.97%)	31 / 154 (20.13%)	2 / 77 (2.60%)
occurrences all number	15	33	2
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	22 / 156 (14.10%)	8 / 154 (5.19%)	13 / 77 (16.88%)
occurrences all number	22	9	13
Infections and infestations
Nasopharyngitis
subjects affected / exposed	23 / 156 (14.74%)	18 / 154 (11.69%)	8 / 77 (10.39%)
occurrences all number	24	18	11
Upper respiratory tract infection
subjects affected / exposed	11 / 156 (7.05%)	11 / 154 (7.14%)	5 / 77 (6.49%)
occurrences all number	12	11	6

More information

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Were there any global substantial amendments to the protocol? Yes

03 Nov 2017

Electrocardiography (ECG) exclusion criteria, and discontinuation criteria were added for subject safety until further evaluation of QT data for Janus kinase 1 (JAK1) was obtained. Revisions to planned ECG assessments included addition of single ECG assessments at study visits 4, 5, 7 and follow-up, clarification that the baseline ECG was routinely performed for all subjects, revision of exclusion criterion was to exclude additional factors associated with QT/ QT interval with Fridericia’s correction (QTcF) abnormalities and confirmation that Fridericia’s correction was used, and addition of a discontinuation criterion for prolonged QTcF interval.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy and Safety of PF-04965842 Monotherapy in Subjects Aged 12 Years and Older, With Moderate to Severe Atopic Dermatitis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)

Secondary: Percentage of Subjects With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set

Secondary: Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus

Secondary: Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Children’s Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Children’s Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Children’s Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Secondary: Percentage of Subjects With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Clinical Trial Results:
Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy and Safety of PF-04965842 Monotherapy in Subjects Aged 12 Years and Older, With Moderate to Severe Atopic Dermatitis