Study to Assess Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Participants Aged ≥2 Years With Mild to Moderate Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT03954158
• Recruitment Status: Completed
• First Posted: May 17, 2019
• Results First Posted: July 14, 2020
• Last Update Posted: July 14, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis
• Interventions: Drug: Crisaborole ointment 2%; Drug: Vehicle
• Enrollment: 81

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
Arm/Group Description	Participants in this reporting arm were of age greater than or equal to (>=) 12 years. Investigator determined 2 target lesions of same atopic dermatitis (AD) severity in each participant at baseline (Day 1). Crisaborole ointment 2 percent (%) was applied once daily (QD) to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied twice daily (BID) to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).
Period Title: Overall Study
Started	20	21	20	20
Completed	20	21	20	20
Not Completed	0	0	0	0

Baseline Characteristics

Arm/Group Title		Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years	Total
Arm/Group Description		Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Total of all reporting groups
Overall Number of Baseline Participants		20	21	20	20	81
Baseline Analysis Population Description		Full analysis set (FAS) included all participants who were randomized and received >=1 dose of investigational product.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	21 participants	20 participants	20 participants	81 participants
	<=18 years	1 5.0%	0 0.0%	20 100.0%	20 100.0%	41 50.6%
	Between 18 and 65 years	19 95.0%	21 100.0%	0 0.0%	0 0.0%	40 49.4%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	21 participants	20 participants	20 participants	81 participants
	Female	11 55.0%	17 81.0%	8 40.0%	11 55.0%	47 58.0%
	Male	9 45.0%	4 19.0%	12 60.0%	9 45.0%	34 42.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	21 participants	20 participants	20 participants	81 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	20 100.0%	21 100.0%	20 100.0%	20 100.0%	81 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	21 participants	20 participants	20 participants	81 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	20 100.0%	21 100.0%	20 100.0%	20 100.0%	81 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle
Description	Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product.

Arm/Group Title	Crisaborole 2% QD: Age Group >=12 Years	Vehicle QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Vehicle BID: Age Group >=12 Years	Crisaborole 2% QD: Age Group 2 to 11 Years	Vehicle QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years	Vehicle BID: Age Group 2 to 11 Years
Arm/Group Description:	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	20	21	21	20	20	20	20
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	7.7 (0.36)	7.5 (0.45)	7.1 (0.46)	7.4 (0.48)	6.2 (0.38)	6.5 (0.37)	7.1 (0.45)	7.3 (0.44)
Change at Day 15	-4.5 (0.60)	-2.9 (0.51)	-4.8 (0.53)	-2.7 (0.47)	-3.5 (0.47)	-2.0 (0.50)	-4.7 (0.50)	-2.6 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures (MMRM) included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0071
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.53
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0029
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -3.3 to -0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0250
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0014
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -3.3 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.56
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD
Description	Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product.

Arm/Group Title	Crisaborole 2% QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Crisaborole 2% QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years
Arm/Group Description:	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	21	20	20
Least Squares Mean (95% Confidence Interval); Unit of Measure: units on a scale
	-4.3; (-5.4 to -3.3)	-4.9; (-5.9 to -3.9)	-3.7; (-4.5 to -2.8)	-4.5; (-5.4 to -3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4295
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.1 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.61
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Total Sign Score in Target Lesions at Day 8: Crisaborole Ointment 2% Versus Vehicle
Description	Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity.
Time Frame	Baseline, Day 8

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product. Here, "Number Analyzed" signifies number of participants evaluable at specified time points.

Arm/Group Title		Crisaborole 2% QD: Age Group >=12 Years	Vehicle QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Vehicle BID: Age Group >=12 Years	Crisaborole 2% QD: Age Group 2 to 11 Years	Vehicle QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years	Vehicle BID: Age Group 2 to 11 Years
Arm/Group Description:		Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed		20	20	21	21	20	20	20	20
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	Number Analyzed	20 participants	20 participants	21 participants	21 participants	20 participants	20 participants	20 participants	20 participants
		7.7 (0.36)	7.5 (0.45)	7.1 (0.46)	7.4 (0.48)	6.2 (0.38)	6.5 (0.37)	7.1 (0.45)	7.3 (0.44)
Change at Day 8	Number Analyzed	20 participants	20 participants	21 participants	21 participants	19 participants	19 participants	20 participants	20 participants
		-3.9 (0.49)	-2.0 (0.40)	-3.7 (0.53)	-2.3 (0.35)	-3.2 (0.34)	-1.9 (0.40)	-3.7 (0.46)	-2.0 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.56
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.55
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.69
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.2 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Investigator's Static Global Assessment (ISGA) Score in Target Lesions at Day 8 and Day 15
Description	ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicated higher degree of AD. Grades for classification of severity: 0= clear (minor residual hypo/hyper pigmentation, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting).
Time Frame	Baseline, Day 8, Day 15

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product. Here, "Number Analyzed" signifies number of participants evaluable at specified time points.

Arm/Group Title		Crisaborole 2% QD: Age Group >=12 Years	Vehicle QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Vehicle BID: Age Group >=12 Years	Crisaborole 2% QD: Age Group 2 to 11 Years	Vehicle QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years	Vehicle BID: Age Group 2 to 11 Years
Arm/Group Description:		Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed		20	20	21	21	20	20	20	20
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	Number Analyzed	20 participants	20 participants	21 participants	21 participants	20 participants	20 participants	20 participants	20 participants
		3.0 (0.0)	3.0 (0.0)	3.0 (0.0)	3.0 (0.0)	3.0 (0.0)	3.0 (0.0)	3.0 (0.0)	3.0 (0.0)
Change at Day 8	Number Analyzed	20 participants	20 participants	21 participants	21 participants	19 participants	19 participants	20 participants	20 participants
		-1.3 (0.18)	-0.8 (0.12)	-1.1 (0.20)	-0.7 (0.12)	-1.4 (0.19)	-1.0 (0.20)	-1.2 (0.18)	-0.8 (0.16)
Change at Day 15	Number Analyzed	20 participants	20 participants	21 participants	21 participants	20 participants	20 participants	20 participants	20 participants
		-1.9 (0.19)	-1.0 (0.15)	-1.9 (0.19)	-1.1 (0.19)	-1.8 (0.22)	-1.1 (0.19)	-1.9 (0.16)	-0.9 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.23
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.20
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.22
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 15, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Vehicle QD: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 15, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Target Lesions up to Day 15 in Participants Aged 12 Years or More
Description	The severity of itch (pruritus) due to AD at the target lesion was assessed using the peak pruritus NRS. Participants aged 12 years or more, were asked to rate their itch severity at the worst moment during the past 24 hours on a scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch.
Time Frame	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product.

Arm/Group Title	Crisaborole 2% QD: Age Group >=12 Years	Vehicle QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Vehicle BID: Age Group >=12 Years
Arm/Group Description:	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	20	21	21
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	5.3 (0.59)	5.3 (0.57)	5.1 (0.47)	5.3 (0.43)
Change at Day 2	-1.3 (0.45)	-0.7 (0.38)	-0.6 (0.20)	-0.5 (0.37)
Change at Day 3	-1.7 (0.51)	-1.1 (0.49)	-1.4 (0.30)	-1.2 (0.36)
Change at Day 4	-2.5 (0.53)	-1.2 (0.55)	-2.0 (0.32)	-1.2 (0.44)
Change at Day 5	-2.6 (0.54)	-1.5 (0.46)	-2.6 (0.37)	-1.8 (0.40)
Change at Day 6	-2.8 (0.48)	-1.6 (0.51)	-2.2 (0.45)	-1.9 (0.46)
Change at Day 7	-2.9 (0.50)	-1.7 (0.56)	-2.5 (0.39)	-2.1 (0.45)
Change at Day 8	-3.2 (0.49)	-2.0 (0.56)	-2.8 (0.40)	-2.2 (0.48)
Change at Day 9	-3.2 (0.51)	-1.6 (0.55)	-2.7 (0.57)	-2.3 (0.46)
Change at Day 10	-3.3 (0.53)	-1.7 (0.61)	-3.0 (0.44)	-2.0 (0.58)
Change at Day 11	-3.5 (0.54)	-2.0 (0.55)	-3.1 (0.41)	-2.3 (0.49)
Change at Day 12	-3.5 (0.60)	-2.3 (0.58)	-3.3 (0.44)	-2.3 (0.50)
Change at Day 13	-3.4 (0.62)	-2.3 (0.57)	-3.5 (0.45)	-2.4 (0.46)
Change at Day 14	-3.3 (0.64)	-2.1 (0.65)	-3.6 (0.43)	-2.6 (0.47)
Change at Day 15	-3.5 (0.63)	-2.0 (0.63)	-3.7 (0.47)	-2.9 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.20
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 2, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 3, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.55
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.38
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 4, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 5, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.37
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 6, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.29
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 7, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 9, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.59
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 10, Inter-participant: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of Least Squares Mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 11, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.7 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 11, Intra-participant: MMRM included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.38
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 11, Inter-participant: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of Least Squares Mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 12, Inter-participant: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of Least Squares Mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.9 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.8 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments	[Not Specified]

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 13, Inter-participant: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of Least Squares Mean
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.53
	Estimation Comments	[Not Specified]

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	[Not Specified]

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.8 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 14, Inter-participant: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of Least Squares Mean
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.53
	Estimation Comments	[Not Specified]

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Vehicle QD: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group >=12 Years, Vehicle BID: Age Group >=12 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group >=12 Years, Crisaborole 2% BID: Age Group >=12 Years
	Comments	Change at Day 15, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least square mean
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.53
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in Itch Severity Scale in Target Lesions up to Day 15 in Participants Aged Between 6 to 11 Years
Description	The itch severity scale was used for participants >=6 to 11 years of age to assess severity of itch (pruritus) due to AD at the target lesion. In this assessment, participants were asked to choose a unit that showed how itchy their skin had been on day of assessment on a 5-point scale ranging from 1= not itchy to 5= very itchy, where higher scores represented more severe itch.
Time Frame	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who were randomized and received greater than or equal to 1 dose of investigational product and aged between 6 to 11 years. Here, "Overall Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Arm/Group Title	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years	Vehicle QD Sub-group: Age Group 6 to 11 Years	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years	Vehicle BID Sub-group: Age Group 6 to 11 Years
Arm/Group Description:	Participants in this sub-group were of age 6 to 11 Years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this sub-group were of age 6 to 11 Years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this sub-group were of age 6 to 11 Years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this sub-group were of age 6 to 11 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	16	16	14	14
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	1.6 (0.33)	1.8 (0.32)	1.9 (0.33)	1.6 (0.34)
Change at Day 2	-0.7 (0.36)	-0.3 (0.35)	-0.6 (0.45)	-0.4 (0.44)
Change at Day 3	-0.4 (0.35)	-0.5 (0.26)	-0.9 (0.30)	-0.3 (0.46)
Change at Day 4	-0.4 (0.45)	-0.4 (0.32)	-0.7 (0.46)	-0.7 (0.46)
Change at Day 5	-0.6 (0.41)	-0.1 (0.35)	-0.7 (0.47)	-0.3 (0.30)
Change at Day 6	-0.8 (0.37)	-0.4 (0.34)	-0.9 (0.38)	-0.8 (0.33)
Change at Day 7	-0.3 (0.46)	-0.3 (0.31)	-0.9 (0.45)	-0.8 (0.43)
Change at Day 8	-1.1 (0.30)	-0.7 (0.36)	-1.1 (0.44)	-0.6 (0.37)
Change at Day 9	-0.6 (0.38)	-0.3 (0.31)	-1.4 (0.37)	-1.0 (0.26)
Change at Day 10	-0.8 (0.37)	-0.4 (0.34)	-1.1 (0.33)	-0.9 (0.32)
Change at Day 11	-1.1 (0.34)	-0.5 (0.38)	-1.1 (0.49)	-0.7 (0.32)
Change at Day 12	-0.8 (0.32)	0.1 (0.40)	-1.4 (0.37)	-0.7 (0.45)
Change at Day 13	-0.8 (0.37)	-0.2 (0.34)	-1.4 (0.37)	-0.7 (0.44)
Change at Day 14	-0.9 (0.36)	-0.4 (0.31)	-1.3 (0.41)	-1.0 (0.36)
Change at Day 15	-0.8 (0.38)	-0.6 (0.26)	-1.3 (0.44)	-0.9 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 2, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 3, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 96%; -1.1 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 4, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 5, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 6, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 7, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 9, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 10, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 11, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 11, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 11, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments	[Not Specified]

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 12, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.37
	Estimation Comments	[Not Specified]

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 13, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 14, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments	[Not Specified]

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Vehicle QD Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years, Vehicle BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years, Crisaborole 2% BID Sub-group: Age Group 6 to 11 Years
	Comments	Change at Day 15, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in Observer Reported Itch Severity Numerical Rating Scale in Target Lesions up to Day 15 in Participants Aged Between 2 to 11 Years
Description	Observer reported itch severity NRS was used for participants >=2 and < 12 years of age to assess severity of itch (pruritus) due to AD at the target lesion. Parents/caregivers (of participants) were asked to rate participants' itch (i.e. scratching, rubbing) at the worst moment during past 24 hours on a scale of 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch.
Time Frame	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized and received greater than or equal to 1 dose of investigational product.

Arm/Group Title	Crisaborole 2% QD: Age Group 2 to 11 Years	Vehicle QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years	Vehicle BID: Age Group 2 to 11 Years
Arm/Group Description:	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	20	20	20
Mean (Standard Error); Unit of Measure: units on a scale
Baseline	4.7 (0.56)	5.0 (0.50)	5.5 (0.56)	5.1 (0.56)
Change at Day 2	-0.5 (0.30)	-0.4 (0.31)	-0.7 (0.40)	-0.9 (0.50)
Change at Day 3	-0.7 (0.28)	-0.5 (0.35)	-1.6 (0.47)	-1.3 (0.55)
Change at Day 4	-0.5 (0.51)	-0.4 (0.38)	-1.8 (0.64)	-1.6 (0.58)
Change at Day 5	-1.4 (0.48)	-0.1 (0.60)	-2.0 (0.66)	-2.1 (0.52)
Change at Day 6	-1.9 (0.45)	-0.9 (0.43)	-2.7 (0.62)	-2.2 (0.66)
Change at Day 7	-2.0 (0.40)	-0.9 (0.45)	-3.0 (0.64)	-1.9 (0.71)
Change at Day 8	-2.3 (0.41)	-1.3 (0.36)	-3.3 (0.66)	-2.0 (0.70)
Change at Day 9	-2.0 (0.50)	-0.8 (0.42)	-3.4 (0.61)	-2.5 (0.63)
Change at Day 10	-2.2 (0.39)	-0.9 (0.42)	-3.9 (0.62)	-2.3 (0.65)
Change at Day 11	-2.4 (0.43)	-1.1 (0.45)	-3.5 (0.69)	-2.4 (0.66)
Change at Day 12	-2.1 (0.45)	-0.7 (0.61)	-4.1 (0.60)	-2.5 (0.65)
Change at Day 13	-2.1 (0.55)	-1.0 (0.50)	-4.1 (0.54)	-2.6 (0.70)
Change at Day 14	-2.4 (0.48)	-1.2 (0.49)	-4.3 (0.56)	-2.8 (0.66)
Change at Day 15	-2.5 (0.55)	-1.3 (0.45)	-4.3 (0.63)	-3.0 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 2, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 2, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 3, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.58
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 3, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.53
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 4, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.62
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 4, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.39
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 5, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.3 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.66
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 5, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 6, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 6, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.7 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.63
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 7, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.48
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 7, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.61
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 8, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.64
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 9, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.49
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 9, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.63
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 10, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.5 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 10, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.58
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 11, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 11, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.51
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 11, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.2 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.67
	Estimation Comments	[Not Specified]

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.9 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 12, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 12, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.9 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.63
	Estimation Comments	[Not Specified]

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.5 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.68
	Estimation Comments	[Not Specified]

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 13, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.44
	Estimation Comments	[Not Specified]

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 13, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.0 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.62
	Estimation Comments	[Not Specified]

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.5 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.45
	Estimation Comments	[Not Specified]

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 14, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.59
	Estimation Comments	[Not Specified]

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 14, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.62
	Estimation Comments	[Not Specified]

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Vehicle QD: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.57
	Estimation Comments	[Not Specified]

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% BID: Age Group 2 to 11 Years, Vehicle BID: Age Group 2 to 11 Years
	Comments	Change at Day 15, Intra-participant: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean of difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	[Not Specified]

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Crisaborole 2% QD: Age Group 2 to 11 Years, Crisaborole 2% BID: Age Group 2 to 11 Years
	Comments	Change at Day 15, Inter-participant: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference of least squares mean
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.66
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) in the Target Lesions Per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term
Description	An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. For this outcome measure, treatment-emergent AEs occurred at each treated target lesion were summarized. MedDRA version 22.1 coding dictionary was used.
Time Frame	Day 1 up to 35 days after end of treatment (maximum up to Day 50)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants receiving greater than or equal to 1 dose of investigational product. Treatment emergent AEs and SAEs occurred in the target lesions were planned to be summarized by treatment in each regimen for each cohort and pooled cohort.

Arm/Group Title	Crisaborole 2% QD: Age Group >=12 Years	Vehicle QD: Age Group >=12 Years	Crisaborole 2% BID: Age Group >=12 Years	Vehicle BID: Age Group >=12 Years	Crisaborole 2% QD: Age Group 2 to 11 Years	Vehicle QD: Age Group 2 to 11 Years	Crisaborole 2% BID: Age Group 2 to 11 Years	Vehicle BID: Age Group 2 to 11 Years	Crisaborole 2% QD: All Age Group	Vehicle QD: All Age Group	Crisaborole 2% BID: All Age Group	Vehicle BID: All Age Group
Arm/Group Description:	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same atopic dermatitis severity in each participant at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Vehicle was applied QD to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).	Vehicle was applied BID to 1 of the target lesions for 15 days and participants were followed up to 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	20	21	21	20	20	20	20	40	40	41	41
Measure Type: Count of Participants; Unit of Measure: Participants
Application site coldness	0 0.0%	0 0.0%	0 0.0%	1 4.8%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.4%
Application site irritation	2 10.0%	1 5.0%	4 19.0%	1 4.8%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 5.0%	1 2.5%	4 9.8%	1 2.4%
Application site pain	1 5.0%	0 0.0%	1 4.8%	0 0.0%	0 0.0%	0 0.0%	1 5.0%	0 0.0%	1 2.5%	0 0.0%	2 4.9%	0 0.0%
Application site pruritus	2 10.0%	2 10.0%	1 4.8%	1 4.8%	0 0.0%	0 0.0%	1 5.0%	0 0.0%	2 5.0%	2 5.0%	2 4.9%	1 2.4%
Application site folliculitis	1 5.0%	0 0.0%	1 4.8%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.5%	0 0.0%	1 2.4%	0 0.0%

9. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) by Treatment Regimen
Description	An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Day 1 up to 35 days after end of treatment (maximum up to Day 50)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants receiving greater than or equal to 1 dose of investigational product.

Arm/Group Title	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
Arm/Group Description:	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).
Overall Number of Participants Analyzed	20	21	20	20
Measure Type: Count of Participants; Unit of Measure: Participants
Participants With AEs	6 30.0%	6 28.6%	2 10.0%	2 10.0%
Participants With SAEs	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Adverse Events

Time Frame	Day 1 up to 35 days after end of treatment (maximum up to Day 50)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
Arm/Group Description	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions and vehicle was applied QD to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).	Participants in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each participant at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions and vehicle was applied BID to another target lesion (intra-participant) for 15 days and participants were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).
All-Cause Mortality
	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/20 (0.00%)	0/21 (0.00%)	0/20 (0.00%)	0/20 (0.00%)
Serious Adverse Events
	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/20 (0.00%)	0/21 (0.00%)	0/20 (0.00%)	0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/20 (30.00%)	6/21 (28.57%)	2/20 (10.00%)	2/20 (10.00%)
Gastrointestinal disorders
Dental caries * 1	1/20 (5.00%)	0/21 (0.00%)	0/20 (0.00%)	0/20 (0.00%)
General disorders
Application site coldness * 1	0/20 (0.00%)	1/21 (4.76%)	0/20 (0.00%)	0/20 (0.00%)
Application site irritation * 1	3/20 (15.00%)	4/21 (19.05%)	0/20 (0.00%)	0/20 (0.00%)
Application site pain * 1	1/20 (5.00%)	1/21 (4.76%)	0/20 (0.00%)	1/20 (5.00%)
Application site pruritus * 1	3/20 (15.00%)	2/21 (9.52%)	0/20 (0.00%)	1/20 (5.00%)
Infections and infestations
Application site folliculitis * 1	1/20 (5.00%)	1/21 (4.76%)	0/20 (0.00%)	0/20 (0.00%)
Hand-foot-and-mouth disease * 1	0/20 (0.00%)	0/21 (0.00%)	1/20 (5.00%)	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/20 (0.00%)	0/21 (0.00%)	1/20 (5.00%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain * 1	0/20 (0.00%)	3/21 (14.29%)	0/20 (0.00%)	0/20 (0.00%)
1 Term from vocabulary, MedDRA 22.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03954158
• Other Study ID Numbers: C3291028
• First Submitted: May 15, 2019
• First Posted: May 17, 2019
• Results First Submitted: May 27, 2020
• Results First Posted: July 14, 2020
• Last Update Posted: July 14, 2020