Clinical Trial Results:
A Phase 2B, MultiCenter, Randomized, DoubleBlind, Vehicle Controlled, IntraSubjects Study, to Evaluate Efficacy and Safety of two Regimens of Crisaborole Ointment 2% in Japanese Pediatric and Adult Subjects (2 Years and Older) With Mild to Moderate Atopic Dermatitis
Summary


EudraCT number 
202000087520 
Trial protocol 
Outside EU/EEA 
Global end of trial date 
16 Dec 2019

Results information


Results version number 
v1(current) 
This version publication date 
12 Jun 2020

First version publication date 
12 Jun 2020

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


Trial identification


Sponsor protocol code 
C3291028


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT03954158  
WHO universal trial number (UTN) 
  
Other trial identifiers 
JapicCTI: JapicCTI194776  
Sponsors


Sponsor organisation name 
Pfizer Inc.


Sponsor organisation address 
235 E 42nd Street, New York, United States, 10017


Public contact 
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com


Scientific contact 
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


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


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


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
13 Apr 2020


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
16 Dec 2019


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
To compare the efficacy of crisaborole ointment 2%, administered QD or BID relative to the corresponding vehicle (QD or BID), on Total Sign Score (TSS) assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
To evaluate the efficacy of crisaborole ointment 2% BID relative to crisaborole ointment 2% QD, on TSS assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
To evaluate the efficacy of crisaborole ointment 2%, administered QD or BID, on TSS, ISGA and Pruritus assessments in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2).
To assess the safety and local tolerability of crisaborole ointment 2%, administered QD or BID, in the treatment of mild to moderate AD in adults (cohort 1) and pediatrics (cohort 2)


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


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
15 Jun 2019


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Japan: 81


Worldwide total number of subjects 
81


EEA total number of subjects 
0


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
40


Adolescents (1217 years) 
0


Adults (1864 years) 
41


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


Screening details 
The study was conducted for a total of 81 subjects between 15 June 2019 and 16 December 2019.  
Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Arms


Are arms mutually exclusive 
Yes


Arm title

Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years  
Arm description 
Subjects 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 subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Arm type 
Experimental  
Investigational medicinal product name 
Crisaborole 2%


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Crisaborole ointment 2 % was applied QD to 1 of the target lesions.


Investigational medicinal product name 
Vehicle


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Vehicle was applied QD to 1 of target lesions.


Arm title

Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years  
Arm description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Arm type 
Experimental  
Investigational medicinal product name 
Crisaborole 2 %


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Crisaborole ointment 2 % was applied BID to 1 of the target lesions.


Investigational medicinal product name 
Vehicle


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Vehicle was applied BID to 1 of target lesions.


Arm title

Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 211 years  
Arm description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Arm type 
Experimental  
Investigational medicinal product name 
Vehicle


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Vehicle was applied QD to 1 of target lesions.


Investigational medicinal product name 
Crisaborole 2%


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Crisaborole ointment 2% was applied QD to 1 of the target lesions.


Arm title

Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 211 years  
Arm description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Arm type 
Experimental  
Investigational medicinal product name 
Crisaborole 2%


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Crisaborole ointment 2% was applied BID to 1 of the target lesions.


Investigational medicinal product name 
Vehicle


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Ointment


Routes of administration 
Topical use


Dosage and administration details 
Vehicle was applied BID to 1 of target lesions.





Baseline characteristics reporting groups


Reporting group title 
Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years


Reporting group description 
Subjects 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 subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years


Reporting group description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  



End points reporting groups


Reporting group title 
Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years


Reporting group description 
Subjects 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 subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years


Reporting group description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Subject analysis set title 
Crisaborole 2% QD: Age group >=12 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle QD: Age group >=12 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% BID: Age group >=12 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle BID: Age group >=12 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% QD: Age group 2 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle QD: Age group 2 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% BID: Age group 2 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle BID: Age group 2 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this reporting arm were of age 2 to 11. Investigator determined 2 target lesions of same BID severity in each subject at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% QD: All age group


Subject analysis set type 
Full analysis  
Subject analysis set description 
Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle QD: All age group


Subject analysis set type 
Full analysis  
Subject analysis set description 
Vehicle was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% BID: All age group


Subject analysis set type 
Full analysis  
Subject analysis set description 
Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle BID: All age group


Subject analysis set type 
Full analysis  
Subject analysis set description 
Vehicle was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this subgroup were of age 6 to 11 Years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle QD Subgroup: Age group 6 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this subgroup were of age 6 to 11 Years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Vehicle was applied QD to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this subgroup were of age 6 to 11 Years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Crisaborole ointment 2% was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).


Subject analysis set title 
Vehicle BID Subgroup: Age group 6 to 11 years


Subject analysis set type 
Full analysis  
Subject analysis set description 
Subjects in this subgroup were of age 6 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject at baseline (Day 1). Vehicle was applied BID to 1 of the target lesions for 15 days and subjects were followed up to 35 days after the end of treatment (maximum up to Day 50).



End point title 
Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle  
End point 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. FAS included all subjects who were randomized and received greater than or equal to 1 dose of investigational product.


End point type 
Primary


End point timeframe 
Baseline, Day 15




Statistical analysis title 
Crisaborole QD: >=12 yrs vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures (MMRM) included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
superiority ^{[1]}  
Pvalue 
= 0.0071  
Method 
Mixed models analysis  
Parameter type 
Least square mean of difference  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.53


Notes [1]  This was an intraparticipant comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
superiority ^{[2]}  
Pvalue 
= 0.0029  
Method 
Mixed models analysis  
Parameter type 
Least square mean of difference  
Point estimate 
2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.3  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.6


Notes [2]  This was an intraparticipant comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
superiority ^{[3]}  
Pvalue 
= 0.025  
Method 
Mixed models analysis  
Parameter type 
Least squares mean of difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.6


Notes [3]  This was an intraparticipant comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
superiority ^{[4]}  
Pvalue 
= 0.0014  
Method 
Mixed models analysis  
Parameter type 
Least squares mean of difference  
Point estimate 
2.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.3  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.56


Notes [4]  This was an intraparticipant comparison. Hence the actual number of subjects involved in the analysis was 20. 


End point title 
Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD  
End point 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. FAS included all subjects who were randomized and received greater than or equal to 1 dose of investigational product.


End point type 
Secondary


End point timeframe 
Baseline, Day 15




Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4295


Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.61



End point title 
Change From Baseline in Total Sign Score in Target Lesions at Day 8: Crisaborole Ointment 2% Versus Vehicle  
End point 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. FAS included all subjects who were randomized and received greater than or equal to 1 dose of investigational product. Here, “n” signifies number of subjects evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Baseline, Day 8




Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[5]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.1  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.56


Notes [5]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[6]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.7  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.6


Notes [6]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[7]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.49


Notes [7]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[8]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.55


Notes [8]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
1.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.69


Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.54



End point title 
Change from Baseline in Investigator's Static Global Assessment (ISGA) Score in Target Lesions at Day 8 and Day 15  
End point description 
ISGA assessed the severity of AD on a 5point 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 (pinkred 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). FAS included all subjects who were randomized and received greater than or equal to 1 dose of investigational product. Here, “n” signifies number of subjects evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Baseline, Day 8, Day 15




Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[9]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.17


Notes [9]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 8, Intrasuject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[10]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.21


Notes [10]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[11]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.23


Notes [11]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[12]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.2


Notes [12]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.27


Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.26


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[13]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.22


Notes [13]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[14]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.25


Notes [14]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[15]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.24


Notes [15]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of visit, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[16]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.21


Notes [16]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 15, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.27


Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 15, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimenbyvisit interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.28



End point title 
Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Target Lesions up to Day 15 in Subjects Aged 12 Years or More  
End point description 
The severity of itch (pruritus) due to AD at the target lesion was assessed using the peak pruritus NRS. Subjects 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 subjects who were randomized and received greater than or equal to 1 dose of investigational product.


End point type 
Secondary


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




Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 2, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[17]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.2


Notes [17]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 2, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[18]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.28


Notes [18]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 2, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.54


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[19]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Notes [19]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[20]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Notes [20]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 3, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.55


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrss  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[21]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.38


Notes [21]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[22]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Notes [22]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 4, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.5


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[23]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Notes [23]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[24]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Notes [24]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 5, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[25]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [25]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[26]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.37


Notes [26]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 6, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.51


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[27]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Notes [27]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[28]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.29


Notes [28]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 7, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[29]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Notes [29]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[30]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.35


Notes [30]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[31]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Notes [31]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[32]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Notes [32]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 9, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
1.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.59


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[33]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.31


Notes [33]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[34]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.47


Notes [34]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 10, Intersubject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of Least Squares Mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.49


Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[35]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [35]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: MMRM included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[36]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.38


Notes [36]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 11, Intersubject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of Least Squares Mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[37]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Notes [37]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[38]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.47


Notes [38]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 12, Intersubject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of Least Squares Mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[39]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.35


Notes [39]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[40]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.47


Notes [40]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 13, Intersubject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of Least Squares Mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.53


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[41]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.31


Notes [41]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[42]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [42]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 14, Intersubject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of Least Squares Mean  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.53


Statistical analysis title 
Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Vehicle QD: Age group >=12 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[43]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Notes [43]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: >=12yrs Vs Vehicle BID: >=12yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures included the fixed effect of day, and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group >=12 years v Vehicle BID: Age group >=12 years


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
other ^{[44]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Notes [44]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 21. 

Statistical analysis title 
CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs  
Statistical analysis description 
Change at Day 15, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimenbyday interaction, and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group >=12 years v Crisaborole 2% BID: Age group >=12 years


Number of subjects included in analysis 
41


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least square mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.53



End point title 
Change From Baseline in Itch Severity Scale in Target Lesions up to Day 15 in Subjects Aged Between 6 to 11 Years  
End point description 
The itch severity scale was used for subjects >=6 to 11 years of age to assess severity of itch (pruritus) due to AD at the target lesion. In this assessment, subjects were asked to choose a unit that showed how itchy their skin had been on day of assessment on a 5point scale ranging from 1= not itchy to 5= very itchy, where higher scores represented more severe itch. Analysis population included all subjects who were randomized and received greater than or equal to 1 dose of investigational product and aged between 6 to 11 years. Here, “Number of subjects Analyzed” signifies number of subjects evaluable for this endpoint.


End point type 
Secondary


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




Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 2, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[45]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.27


Notes [45]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 2, Intrasubjects: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[46]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [46]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 2, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[47]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.3


Notes [47]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[48]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [48]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 3, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[49]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0


Confidence interval 

level 
96%  
sides 
2sided


lower limit 
1.1  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Notes [49]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[50]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [50]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 4, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.43


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[51]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Notes [51]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[52]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [52]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 5, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[53]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [53]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[54]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [54]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 6, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.33


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[55]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.9  
Variability estimate 
Standard error of the mean


Dispersion value 
0.43


Notes [55]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[56]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [56]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 7, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[57]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [57]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[58]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [58]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.32


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[59]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Notes [59]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[60]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [60]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 9, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.33


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[61]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Notes [61]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[62]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [62]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 10, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.31


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[63]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.6  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Notes [63]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 11, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[64]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [64]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[65]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.43


Notes [65]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[66]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [66]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 12, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.37


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[67]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Notes [67]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[68]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [68]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 13, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[69]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [69]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[70]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [70]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 14, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.39


Statistical analysis title 
Crisaborole QD: 611yrs Vs Vehicle QD: 611yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Vehicle QD Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
32


Analysis specification 
Prespecified


Analysis type 
other ^{[71]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.34


Notes [71]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 16. 

Statistical analysis title 
Crisaborole BID: 611yrs Vs Vehicle BID: 611yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.


Comparison groups 
Crisaborole 2% BID Subgroup: Age group 6 to 11 years v Vehicle BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
28


Analysis specification 
Prespecified


Analysis type 
other ^{[72]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.41


Notes [72]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 14. 

Statistical analysis title 
Crisaborole QD:611yrs Vs Crisaborole BID:611yrs  
Statistical analysis description 
Change at Day 15, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD Subgroup: Age group 6 to 11 Years v Crisaborole 2% BID Subgroup: Age group 6 to 11 years


Number of subjects included in analysis 
30


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.39



End point title 
Change From Baseline in Observer Reported Itch Severity Numerical Rating Scale in Target Lesions up to Day 15 in Subjects Aged Between 2 to 11 years  
End point description 
Observer reported itch severity NRS was used for subjects >=2 and < 12 years of age to assess severity of itch (pruritus) due to AD at the target lesion. Parents/caregivers (of subjects) were asked to rate subjects’ 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 subjects who were randomized and received greater than or equal to 1 dose of investigational product.


End point type 
Secondary


End point timeframe 
Baseline, Day 15




Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 2, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[73]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.39


Notes [73]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 2, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[74]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.36


Notes [74]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 2, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.8  
upper limit 
1.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.5


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[75]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.33


Notes [75]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 3, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[76]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.58


Notes [76]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 3, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.6  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.53


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[77]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.1  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Notes [77]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 4, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[78]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
1.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.62


Notes [78]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 4, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.74


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[79]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.39


Notes [79]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 5, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[80]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.3  
upper limit 
1.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.66


Notes [80]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 5, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
1.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.7


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[81]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.46


Notes [81]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 6, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[82]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.4  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.47


Notes [82]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 6, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
0.8  
Variability estimate 
Standard error of the mean


Dispersion value 
0.63


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[83]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.42


Notes [83]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 7, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[84]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.48


Notes [84]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 7, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.61


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[85]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.49


Notes [85]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 8, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[86]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.52


Notes [86]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 8, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.64


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[87]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.54


Notes [87]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 9, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[88]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.9  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.49


Notes [88]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 9, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.63


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[89]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.54


Notes [89]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 10, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[90]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Notes [90]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 10, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.6  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.58


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[91]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.54


Notes [91]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 11, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[92]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.51


Notes [92]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 11, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.67


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[93]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.9  
upper limit 
0  
Variability estimate 
Standard error of the mean


Dispersion value 
0.7


Notes [93]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 12, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[94]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.7  
Variability estimate 
Standard error of the mean


Dispersion value 
0.4


Notes [94]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 12, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.9  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.63


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[95]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.68


Notes [95]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 13, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[96]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.44


Notes [96]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 13, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3  
upper limit 
0.5  
Variability estimate 
Standard error of the mean


Dispersion value 
0.62


Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[97]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.6  
Variability estimate 
Standard error of the mean


Dispersion value 
0.45


Notes [97]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 14, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.59


Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 14, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[98]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.5  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.62


Notes [98]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD: 211yrs Vs Vehicle QD: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Vehicle QD: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[99]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.4  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.57


Notes [99]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole BID: 211yrs Vs Vehicle BID: 211yrs  
Statistical analysis description 
Change at Day 15, Intrasubject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% BID: Age group 2 to 11 years v Vehicle BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other ^{[100]}  
Method 

Parameter type 
Least squares mean of difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.2  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.46


Notes [100]  This was an intrasubject comparison. Hence the actual number of subjects involved in the analysis was 20. 

Statistical analysis title 
Crisaborole QD:211yrs Vs Crisaborole BID:211yrs  
Statistical analysis description 
Change at Day 15, Intersubject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimenbyday interaction and baseline value and the covariance structure UN was used.


Comparison groups 
Crisaborole 2% QD: Age group 2 to 11 years v Crisaborole 2% BID: Age group 2 to 11 years


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Method 

Parameter type 
Difference of least squares mean  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.8  
upper limit 
0.1  
Variability estimate 
Standard error of the mean


Dispersion value 
0.66



End point title 
Number of Subjects With TreatmentEmergent Adverse Events (AEs) in the Target Lesions per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term  
End point description 
An AE was any untoward medical occurrence attributed to a subject who received study drug without regard to possibility of causal relationship. Treatmentemergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pretreatment state. For this endpoint, treatmentemergent AEs occurred at each treated target lesion were summarized. MedDRA version 22.1 coding dictionary was used. Safety analysis set included all subjects receiving greater than or equal to 1 dose of investigational product. Treatment emergent AEs and SAEs occurred in target lesions were planned to be summarized by treatment in each regimen for each cohort and pooled cohort.


End point type 
Secondary


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




No statistical analyses for this end point 


End point title 
Number of Subjects With TreatmentEmergent Adverse Events (AEs) And Serious Adverse Events (SAEs) by Treatment Regimen  
End point description 
An AE was any untoward medical occurrence attributed to a subject 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. Treatmentemergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pretreatment state. Safety analysis set included all subjects receiving greater than or equal to 1 dose of investigational product.


End point type 
Secondary


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




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
Day 1 up to 35 days after end of treatment (maximum up to Day 50)


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
22.1


Reporting groups


Reporting group title 
Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years


Reporting group description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years


Reporting group description 
Subjects in this reporting arm were of age >=12 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subject were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each subject 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  
Reporting group title 
Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 211 years


Reporting group description 
Subjects in this reporting arm were of age 2 to 11 years. Investigator determined 2 target lesions of same AD severity in each Subjects 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 (intrasubject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).  


Frequency threshold for reporting nonserious adverse events: 0%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? No  
Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 