Study to Assess Efficacy and Safety of Two Regimens of Cr... | NCT03954158

Label	Type	Description	Intervention Names
Crisaborole ointment 2% once daily (QD) vs vehicle QD	Experimental	intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2.	Drug: Crisaborole ointment 2% Drug: Vehicle
Crisaborole ointment 2% twice daily (BID) vs vehicle BID	Experimental	Intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2.	Drug: Crisaborole ointment 2% Drug: Vehicle

Name	Type	Description	Arm Group Labels	Other Names
Crisaborole ointment 2%	Drug	BID regimen	Crisaborole ointment 2% twice daily (BID) vs vehicle BID

Measure	Description	Time Frame
Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle	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.	Baseline, Day 15

Measure	Description	Time Frame
Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD	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.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Medical Corporation Heishinkai OPHAC Hospital		Osaka	Osaka	532-0003	Japan
Fukuwa Clinic

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	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).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Dec 19, 2019	May 26, 2020

ID	Title	Description
BG000	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	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).
BG001	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	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).
BG002	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	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).
BG003	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years	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).
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00121 BG00220 BG00320 BG00481

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle

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.

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

Posted

Mean

Standard Error

units on a scale

Baseline, Day 15

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Vehicle QD: Age Group >=12 Years	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).
OG002	Crisaborole 2% BID: Age Group >=12 Years	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).
OG003	Vehicle BID: Age Group >=12 Years	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).
OG004	Crisaborole 2% QD: Age Group 2 to 11 Years	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).
OG005	Vehicle QD: Age Group 2 to 11 Years	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).
OG006	Crisaborole 2% BID: Age Group 2 to 11 Years	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).
OG007	Vehicle BID: Age Group 2 to 11 Years	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).

Units	Counts
Participants	OG00020 OG00120 OG00221 OG003

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0007.7± 0.36 OG0017.5± 0.45 OG0027.1± 0.46 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Mixed Models Analysis		0.0071		Least squares mean of difference	-1.6	Standard Error of the Mean	0.53	2-Sided	95	-2.7	-0.5					Superiority
OG002 OG003

Secondary

Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD

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

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline, Day 15

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Crisaborole 2% BID: Age Group >=12 Years	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).

Secondary

Change From Baseline in Total Sign Score in Target Lesions at Day 8: Crisaborole Ointment 2% Versus Vehicle

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.

Posted

Mean

Standard Error

units on a scale

Baseline, Day 8

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Vehicle QD: Age Group >=12 Years	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).

Secondary

Change From Baseline in Investigator's Static Global Assessment (ISGA) Score in Target Lesions at Day 8 and Day 15

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).

Posted

Mean

Standard Error

units on a scale

Baseline, Day 8, Day 15

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Vehicle QD: Age Group >=12 Years

Secondary

Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Target Lesions up to Day 15 in Participants Aged 12 Years or More

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.

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

Posted

Mean

Standard Error

units on a scale

Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Vehicle QD: Age Group >=12 Years	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).

Secondary

Change From Baseline in Itch Severity Scale in Target Lesions up to Day 15 in Participants Aged Between 6 to 11 Years

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.

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.

Posted

Mean

Standard Error

units on a scale

Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

ID	Title	Description
OG000	Crisaborole 2% QD Sub-group: Age Group 6 to 11 Years	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).
OG001	Vehicle QD Sub-group: Age Group 6 to 11 Years	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).

Secondary

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

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.

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

Posted

Mean

Standard Error

units on a scale

Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group 2 to 11 Years	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).
OG001	Vehicle QD: Age Group 2 to 11 Years	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).

Secondary

Number of Participants With Treatment-Emergent Adverse Events (AEs) in the Target Lesions Per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term

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.

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.

Posted

Count of Participants

Participants

Day 1 up to 35 days after end of treatment (maximum up to Day 50)

ID	Title	Description
OG000	Crisaborole 2% QD: Age Group >=12 Years	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).
OG001	Vehicle QD: Age Group >=12 Years

Secondary

Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) by Treatment Regimen

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.

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

Posted

Count of Participants

Participants

Day 1 up to 35 days after end of treatment (maximum up to Day 50)

ID	Title	Description
OG000	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	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).
OG001	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years

Group IDs	Group Description	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	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.	Least squares mean of difference	-0.6	Standard Error of the Mean	0.20	2-Sided	95	-1.0	-0.2	Other
OG002 OG003	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.	Least squares mean of difference	-0.1	Standard Error of the Mean	0.28	2-Sided	95	-0.7	0.5	Other
OG000 OG002	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.	Difference of least squares mean	0.6	Standard Error of the Mean	0.54	2-Sided	95	-0.5	1.7	Other
OG000 OG001	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.	Least squares mean of difference	-0.6	Standard Error of the Mean	0.32	2-Sided	95	-1.3	0.1	Other
OG002 OG003	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.	Least squares mean of difference	-0.2	Standard Error of the Mean	0.32	2-Sided	95	-0.9	0.4	Other
OG000 OG002	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.	Difference of least square mean	0.2	Standard Error of the Mean	0.55	2-Sided	95	-0.9	1.3	Other
OG000 OG001	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.	Least squares mean of difference	-1.3	Standard Error of the Mean	0.38	2-Sided	95	-2.1	-0.5	Other
OG002 OG003	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.	Least squares mean of difference	-0.8	Standard Error of the Mean	0.34	2-Sided	95	-1.5	-0.1	Other
OG000 OG002	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.	Difference of least square mean	0.4	Standard Error of the Mean	0.50	2-Sided	95	-0.6	1.4	Other
OG000 OG001	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.	Least squares mean of difference	-1.1	Standard Error of the Mean	0.40	2-Sided	95	-1.9	-0.3	Other
OG002 OG003	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.	Least squares mean of difference	-0.8	Standard Error of the Mean	0.34	2-Sided	95	-1.5	-0.1	Other
OG000 OG002	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.	Difference of least square mean	-0.1	Standard Error of the Mean	0.52	2-Sided	95	-1.1	1.0	Other
OG000 OG001	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.	Least squares mean of difference	-1.3	Standard Error of the Mean	0.42	2-Sided	95	-2.1	-0.4	Other
OG002 OG003	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.	Least squares mean of difference	-0.3	Standard Error of the Mean	0.37	2-Sided	95	-1.1	0.4	Other
OG000 OG002	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.	Difference of least square mean	0.5	Standard Error of the Mean	0.51	2-Sided	95	-0.6	1.5	Other
OG000 OG001	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.	Least squares mean of difference	-1.2	Standard Error of the Mean	0.52	2-Sided	95	-2.3	-0.1	Other
OG002 OG003	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.	Least squares mean of difference	-0.4	Standard Error of the Mean	0.29	2-Sided	95	-1.0	0.2	Other
OG000 OG002	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.	Difference of least square mean	0.3	Standard Error of the Mean	0.45	2-Sided	95	-0.6	1.3	Other
OG000 OG001	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.	Least squares mean of difference	-1.2	Standard Error of the Mean	0.40	2-Sided	95	-2.0	-0.3	Other
OG002 OG003	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.	Least squares mean of difference	-0.6	Standard Error of the Mean	0.35	2-Sided	95	-1.3	0.1	Other
OG000 OG002	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.	Difference of least square mean	0.3	Standard Error of the Mean	0.44	2-Sided	95	-0.6	1.2	Other
OG000 OG001	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.	Least squares mean of difference	-1.7	Standard Error of the Mean	0.36	2-Sided	95	-2.4	-0.9	Other
OG002 OG003	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.	Least squares mean of difference	-0.4	Standard Error of the Mean	0.52	2-Sided	95	-1.5	0.7	Other
OG000 OG002	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.	Difference of least square mean	0.5	Standard Error of the Mean	0.59	2-Sided	95	-0.7	1.6	Other
OG000 OG001	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.	Least squares mean of difference	-1.6	Standard Error of the Mean	0.31	2-Sided	95	-2.3	-0.9	Other
OG002 OG003	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.	Least squares mean of difference	-1.1	Standard Error of the Mean	0.47	2-Sided	95	-2.1	-0.1	Other
OG000 OG002	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.	Difference of Least Squares Mean	0.2	Standard Error of the Mean	0.49	2-Sided	95	-0.8	1.2	Other
OG002 OG003	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.	Least squares mean of difference	-0.9	Standard Error of the Mean	0.42	2-Sided	95	-1.7	0.0	Other
OG000 OG001	Change at Day 11, Intra-participant: MMRM included the fixed effect of day, and the covariance structure UN was used.	Least squares mean of difference	-1.5	Standard Error of the Mean	0.38	2-Sided	95	-2.3	-0.7	Other
OG000 OG002	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.	Difference of Least Squares Mean	0.2	Standard Error of the Mean	0.44	2-Sided	95	-0.7	1.1	Other
OG000 OG001	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.	Least squares mean of difference	-1.3	Standard Error of the Mean	0.34	2-Sided	95	-2.0	-0.5	Other
OG002 OG003	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.	Least squares mean of difference	-1.0	Standard Error of the Mean	0.47	2-Sided	95	-2.0	0.0	Other
OG000 OG002	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.	Difference of Least Squares Mean	0.1	Standard Error of the Mean	0.52	2-Sided	95	-0.9	1.2	Other
OG000 OG001	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.	Least squares mean of difference	-1.1	Standard Error of the Mean	0.35	2-Sided	95	-1.8	-0.3	Other
OG002 OG003	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.	Least squares mean of difference	-1.0	Standard Error of the Mean	0.47	2-Sided	95	-2.0	-0.1	Other
OG000 OG002	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.	Difference of Least Squares Mean	-0.2	Standard Error of the Mean	0.53	2-Sided	95	-1.3	0.9	Other
OG000 OG001	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.	Least squares mean of difference	-1.2	Standard Error of the Mean	0.31	2-Sided	95	-1.9	-0.5	Other
OG002 OG003	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.	Least squares mean of difference	-1.0	Standard Error of the Mean	0.42	2-Sided	95	-1.8	-0.1	Other
OG000 OG002	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.	Difference of Least Squares Mean	-0.4	Standard Error of the Mean	0.53	2-Sided	95	-1.5	0.7	Other
OG000 OG001	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.	Least squares mean of difference	-1.5	Standard Error of the Mean	0.34	2-Sided	95	-2.2	-0.8	Other
OG002 OG003	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.	Least squares mean of difference	-0.8	Standard Error of the Mean	0.36	2-Sided	95	-1.5	0.0	Other
OG000 OG002	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.	Difference of least square mean	-0.3	Standard Error of the Mean	0.53	2-Sided	95	-1.4	0.8	Other

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dental caries	Gastrointestinal disorders	MedDRA 22.1	Non-systematic Assessment	EG0001 affected20 at risk EG0010 affected21 at risk EG0020 affected20 at risk EG0030 affected20 at risk
Application site coldness	General disorders	MedDRA 22.1	Non-systematic Assessment	EG0000 affected20 at risk EG0011 affected21 at risk EG0020 affected20 at risk EG003
Application site irritation	General disorders	MedDRA 22.1	Non-systematic Assessment	EG0003 affected20 at risk EG0014 affected21 at risk EG0020 affected20 at risk EG003
Application site pain	General disorders	MedDRA 22.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected21 at risk EG0020 affected20 at risk EG003
Application site pruritus	General disorders	MedDRA 22.1	Non-systematic Assessment	EG0003 affected20 at risk EG0012 affected21 at risk EG0020 affected20 at risk EG003
Application site folliculitis	Infections and infestations	MedDRA 22.1	Non-systematic Assessment	EG0001 affected20 at risk EG0011 affected21 at risk EG0020 affected20 at risk EG003
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 22.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected21 at risk EG0021 affected20 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Non-systematic Assessment	EG0000 affected20 at risk EG0010 affected21 at risk EG0021 affected20 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Non-systematic Assessment	EG0000 affected20 at risk EG0013 affected21 at risk EG0020 affected20 at risk EG003

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: Crisaborole 2% QD + Vehicle QD, Age Group >=12 Years	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).	20	20	6	20
EG001	Cohort 1:Crisaborole 2% BID + Vehicle BID,Age Group >=12 Years	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).	21	21	6	21
EG002	Cohort 2:Crisaborole 2% QD + Vehicle QD, Age Group 2-11 Years	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).	20	20	2	20
EG003	Cohort 2:Crisaborole 2% BID + Vehicle BID,Age Group 2-11 Years	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).	20	20	2	20