Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39572   clinical trials with a EudraCT protocol, of which   6487   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2B, Multi-Center, Randomized, Double-Blind, Vehicle Controlled, Intra-Subjects 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
    2020-000875-20
    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

    Close Top of page
    Trial identification
    Sponsor protocol code
    C3291028
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03954158
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    JapicCTI: JapicCTI-194776
    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 follow-up 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 (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    40
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    41
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    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 (intra-subject) 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 (intra-subject) 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 2-11 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 (intra-subject) 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 2-11 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 (intra-subject) 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.

    Number of subjects in period 1
    Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 2-11 years Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 2-11 years
    Started
    20
    21
    20
    20
    Completed
    20
    21
    20
    20

    Baseline characteristics

    Close Top of page
    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 (intra-subject) 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 (intra-subject) 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 2-11 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 (intra-subject) 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 2-11 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 (intra-subject) 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 values
    Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 2-11 years Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 2-11 years Total
    Number of subjects
    20 21 20 20 81
    Age Categorical
    Units: Subjects
        <=18 years
    1 0 20 20 41
        Between 18 and 65 years
    19 21 0 0 40
        >=65 years
    0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    33.3 ± 10.36 33.9 ± 10.96 7.7 ± 2.52 7.8 ± 2.69 -
    Sex: Female, Male
    Units: Subjects
        Female
    11 17 8 11 47
        Male
    9 4 12 9 34
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0
        Asian
    20 21 20 20 81
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0
        Black or African American
    0 0 0 0 0
        White
    0 0 0 0 0
        More than one race
    0 0 0 0 0
        Unknown or Not Reported
    0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    0 0 0 0 0
        Not Hispanic or Latino
    20 21 20 20 81
        Unknown or Not Reported
    0 0 0 0 0

    End points

    Close Top of page
    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 (intra-subject) 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 (intra-subject) 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 2-11 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 (intra-subject) 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 2-11 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 (intra-subject) 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 Sub-group: Age group 6 to 11 Years
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects in this sub-group 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 Sub-group: Age group 6 to 11 years
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects in this sub-group 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 Sub-group: Age group 6 to 11 years
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects in this sub-group 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 Sub-group: Age group 6 to 11 years
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects in this sub-group 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).

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

    Close Top of page
    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
    End point values
    Crisaborole 2% QD: Age group >=12 years Vehicle QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Vehicle BID: Age group >=12 years Crisaborole 2% QD: Age group 2 to 11 years Vehicle QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years Vehicle BID: Age group 2 to 11 years
    Number of subjects analysed
    20
    20
    21
    21
    20
    20
    20
    20
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline
    7.7 ± 0.36
    7.5 ± 0.45
    7.1 ± 0.46
    7.4 ± 0.48
    6.2 ± 0.38
    6.5 ± 0.37
    7.1 ± 0.45
    7.3 ± 0.44
        Change at Day 15
    -4.5 ± 0.60
    -2.9 ± 0.51
    -4.8 ± 0.53
    -2.7 ± 0.47
    -3.5 ± 0.47
    -2.0 ± 0.50
    -4.7 ± 0.50
    -2.6 ± 0.54
    Statistical analysis title
    Crisaborole QD: >=12 yrs vs Vehicle QD: >=12 yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.0071
    Method
    Mixed models analysis
    Parameter type
    Least square mean of difference
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Notes
    [1] - This was an intra-participant 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, Intra-subject: 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
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.0029
    Method
    Mixed models analysis
    Parameter type
    Least square mean of difference
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.3
         upper limit
    -0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [2] - This was an intra-participant comparison. Hence the actual number of subjects involved in the analysis was 21.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.025
    Method
    Mixed models analysis
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [3] - This was an intra-participant comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.0014
    Method
    Mixed models analysis
    Parameter type
    Least squares mean of difference
    Point estimate
    -2.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.3
         upper limit
    -0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [4] - This was an intra-participant comparison. Hence the actual number of subjects involved in the analysis was 20.

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

    Close Top of page
    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
    End point values
    Crisaborole 2% QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Crisaborole 2% QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years
    Number of subjects analysed
    20
    21
    20
    20
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -4.3 (-5.4 to -3.3)
    -4.9 (-5.9 to -3.9)
    -3.7 (-4.5 to -2.8)
    -4.5 (-5.4 to -3.6)
    Statistical analysis title
    CrisaboroleQD:>=12 yrs Vs CrisaboroleBID:>=12 yrs
    Statistical analysis description
    Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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
    Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61

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

    Close Top of page
    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
    End point values
    Crisaborole 2% QD: Age group >=12 years Vehicle QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Vehicle BID: Age group >=12 years Crisaborole 2% QD: Age group 2 to 11 years Vehicle QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years Vehicle BID: Age group 2 to 11 years
    Number of subjects analysed
    20
    20
    21
    21
    20
    20
    20
    20
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline (n= 20,20,21,21,20,20,20,20)
    7.7 ± 0.36
    7.5 ± 0.45
    7.1 ± 0.46
    7.4 ± 0.48
    6.2 ± 0.38
    6.5 ± 0.37
    7.1 ± 0.45
    7.3 ± 0.44
        Change at Day 8 (n= 20,20,21,21,19,19,20,20)
    -3.9 ± 0.49
    -2.0 ± 0.40
    -3.7 ± 0.53
    -2.3 ± 0.35
    -3.2 ± 0.34
    -1.9 ± 0.40
    -3.7 ± 0.46
    -2.0 ± 0.39
    Statistical analysis title
    Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [5]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.56
    Notes
    [5] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [6]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Notes
    [6] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 21.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [7]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [7] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [8]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.55
    Notes
    [8] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 8, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54

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

    Close Top of page
    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 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicated higher degree of AD. Grades for classification of severity: 0= clear (minor residual hypo/hyper pigmentation, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). 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
    End point values
    Crisaborole 2% QD: Age group >=12 years Vehicle QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Vehicle BID: Age group >=12 years Crisaborole 2% QD: Age group 2 to 11 years Vehicle QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years Vehicle BID: Age group 2 to 11 years
    Number of subjects analysed
    20
    20
    21
    21
    20
    20
    20
    20
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline (n =20,20,21,21,20,20,20,20)
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
    3.0 ± 0.0
        Change at Day 8 (n =20,20,21,21,19,19,20,20)
    -1.3 ± 0.18
    -0.8 ± 0.12
    -1.1 ± 0.20
    -0.7 ± 0.12
    -1.4 ± 0.19
    -1.0 ± 0.20
    -1.2 ± 0.18
    -0.8 ± 0.16
        Change at Day 15 (n =20,20,21,21,20,20,20,20)
    -1.9 ± 0.19
    -1.0 ± 0.15
    -1.9 ± 0.19
    -1.1 ± 0.19
    -1.8 ± 0.22
    -1.1 ± 0.19
    -1.9 ± 0.16
    -0.9 ± 0.20
    Statistical analysis title
    Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [9]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Notes
    [9] - This was an intra-subject 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, Intra-suject: 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
    Pre-specified
    Analysis type
    other [10]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Notes
    [10] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 21.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [11]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23
    Notes
    [11] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [12]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [12] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.27
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 8, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [13]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    -0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.22
    Notes
    [13] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [14]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Notes
    [14] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 21.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    other [15]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Notes
    [15] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    other [16]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Notes
    [16] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.27
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 15, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, visit, dosing regimen-by-visit interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28

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

    Close Top of page
    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
    End point values
    Crisaborole 2% QD: Age group >=12 years Vehicle QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Vehicle BID: Age group >=12 years
    Number of subjects analysed
    20
    20
    21
    21
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline
    5.3 ± 0.59
    5.3 ± 0.57
    5.1 ± 0.47
    5.3 ± 0.43
        Change at Day 2
    -1.3 ± 0.45
    -0.7 ± 0.38
    -0.6 ± 0.20
    -0.5 ± 0.37
        Change at Day 3
    -1.7 ± 0.51
    -1.1 ± 0.49
    -1.4 ± 0.30
    -1.2 ± 0.36
        Change at Day 4
    -2.5 ± 0.53
    -1.2 ± 0.55
    -2.0 ± 0.32
    -1.2 ± 0.44
        Change at Day 5
    -2.6 ± 0.54
    -1.5 ± 0.46
    -2.6 ± 0.37
    -1.8 ± 0.40
        Change at Day 6
    -2.8 ± 0.48
    -1.6 ± 0.51
    -2.2 ± 0.45
    -1.9 ± 0.46
        Change at Day 7
    -2.9 ± 0.50
    -1.7 ± 0.56
    -2.5 ± 0.39
    -2.1 ± 0.45
        Change at Day 8
    -3.2 ± 0.49
    -2.0 ± 0.56
    -2.8 ± 0.40
    -2.2 ± 0.48
        Change at Day 9
    -3.2 ± 0.51
    -1.6 ± 0.55
    -2.7 ± 0.57
    -2.3 ± 0.46
        Change at Day 10
    -3.3 ± 0.53
    -1.7 ± 0.61
    -3.0 ± 0.44
    -2.0 ± 0.58
        Change at Day 11
    -3.5 ± 0.54
    -2.0 ± 0.55
    -3.1 ± 0.41
    -2.3 ± 0.49
        Change at Day 12
    -3.5 ± 0.60
    -2.3 ± 0.58
    -3.3 ± 0.44
    -2.3 ± 0.50
        Change at Day 13
    -3.4 ± 0.62
    -2.3 ± 0.57
    -3.5 ± 0.45
    -2.4 ± 0.46
        Change at Day 14
    -3.3 ± 0.64
    -2.1 ± 0.65
    -3.6 ± 0.43
    -2.6 ± 0.47
        Change at Day 15
    -3.5 ± 0.63
    -2.0 ± 0.63
    -3.7 ± 0.47
    -2.9 ± 0.46
    Statistical analysis title
    Crisaborole QD: >=12 yrs Vs Vehicle QD: >=12 yrs
    Statistical analysis description
    Change at Day 2, Intra-subject: 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
    Pre-specified
    Analysis type
    other [17]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [17] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [18]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28
    Notes
    [18] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [19]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Notes
    [19] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [20]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Notes
    [20] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [21]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.38
    Notes
    [21] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [22]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [22] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [23]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [23] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [24]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [24] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [25]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    -0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [25] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [26]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.37
    Notes
    [26] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [27]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [27] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [28]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29
    Notes
    [28] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [29]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [29] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [30]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.35
    Notes
    [30] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [31]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Notes
    [31] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [32]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [32] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [33]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3
         upper limit
    -0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Notes
    [33] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [34]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [34] - This was an intra-subject 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, Inter-subject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of Least Squares Mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [35]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.7
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [35] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [36]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3
         upper limit
    -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.38
    Notes
    [36] - This was an intra-subject 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, Inter-subject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of Least Squares Mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [37]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [37] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [38]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [38] - This was an intra-subject 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, Inter-subject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of Least Squares Mean
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [39]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.35
    Notes
    [39] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [40]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [40] - This was an intra-subject 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, Inter-subject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of Least Squares Mean
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [41]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Notes
    [41] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [42]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [42] - This was an intra-subject 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, Inter-subject: Mixed effect Model for Repeated Measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value, and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of Least Squares Mean
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [43]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [43] - This was an intra-subject 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, Intra-subject: 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
    Pre-specified
    Analysis type
    other [44]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Notes
    [44] - This was an intra-subject 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, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen, day, dosing regimen-by-day interaction, and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least square mean
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53

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

    Close Top of page
    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 5-point 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
    End point values
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years Vehicle QD Sub-group: Age group 6 to 11 years Crisaborole 2% BID Sub-group: Age group 6 to 11 years Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects analysed
    16
    16
    14
    14
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline
    1.6 ± 0.33
    1.8 ± 0.32
    1.9 ± 0.33
    1.6 ± 0.34
        Change at Day 2
    -0.7 ± 0.36
    -0.33 ± 0.35
    -0.6 ± 0.45
    -0.4 ± 0.44
        Change at Day 3
    -0.4 ± 0.35
    -0.5 ± 0.26
    -0.9 ± 0.30
    -0.3 ± 0.46
        Change at Day 4
    -0.4 ± 0.45
    -0.4 ± 0.32
    -0.7 ± 0.46
    -0.7 ± 0.46
        Change at Day 5
    -0.6 ± 0.41
    -0.1 ± 0.35
    -0.7 ± 0.47
    -0.3 ± 0.30
        Change at Day 6
    -0.8 ± 0.37
    -0.4 ± 0.34
    -0.9 ± 0.38
    -0.8 ± 0.33
        Change at Day 7
    -0.3 ± 0.46
    -0.3 ± 0.31
    -0.9 ± 0.45
    -0.8 ± 0.43
        Change at Day 8
    -1.1 ± 0.30
    -0.7 ± 0.36
    -1.1 ± 0.44
    -0.6 ± 0.37
        Change at Day 9
    -0.6 ± 0.38
    -0.3 ± 0.31
    -1.4 ± 0.37
    -1.0 ± 0.26
        Change at Day 10
    -0.8 ± 0.37
    -0.4 ± 0.34
    -1.1 ± 0.33
    -0.9 ± 0.32
        Change at Day 11
    -1.1 ± 0.34
    -0.5 ± 0.38
    -1.1 ± 0.49
    -0.7 ± 0.32
        Change at Day 12
    -0.8 ± 0.32
    0.1 ± 0.40
    -1.4 ± 0.37
    -0.7 ± 0.45
        Change at Day 13
    -0.8 ± 0.37
    -0.2 ± 0.34
    -1.4 ± 0.37
    -0.7 ± 0.44
        Change at Day 14
    -0.9 ± 0.36
    -0.4 ± 0.31
    -1.3 ± 0.41
    -1.0 ± 0.36
        Change at Day 15
    -0.8 ± 0.38
    -0.6 ± 0.26
    -1.3 ± 0.44
    -0.9 ± 0.38
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 2, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [45]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.27
    Notes
    [45] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 2, Intra-subjects: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [46]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [46] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 2, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 3, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [47]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Notes
    [47] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 3, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [48]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [48] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 3, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 4, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [49]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    0
    Confidence interval
         level
    96%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [49] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 4, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [50]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [50] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 4, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 5, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [51]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Notes
    [51] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 5, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [52]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [52] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 5, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 6, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [53]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [53] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 6, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [54]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [54] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 6, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 7, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [55]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Notes
    [55] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 7, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [56]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [56] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 7, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [57]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [57] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [58]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [58] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 8, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 9, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [59]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [59] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 9, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [60]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [60] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 9, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 10, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [61]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [61] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 10, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [62]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [62] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 10, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 11, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [63]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [63] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 11, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 11, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [64]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [64] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 12, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [65]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Notes
    [65] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 12, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [66]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [66] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 12, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.37
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 13, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [67]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [67] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 13, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [68]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [68] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 13, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 14, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [69]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [69] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 14, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [70]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [70] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 14, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Statistical analysis title
    Crisaborole QD: 6-11yrs Vs Vehicle QD: 6-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: Mixed effect Model for Repeated Measures included the fixed effect of day and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Vehicle QD Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other [71]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [71] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 16.
    Statistical analysis title
    Crisaborole BID: 6-11yrs Vs Vehicle BID: 6-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: Mixed effect model for repeated measures includes the fixed effect of day and the covariance structure AR1 is used.
    Comparison groups
    Crisaborole 2% BID Sub-group: Age group 6 to 11 years v Vehicle BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    other [72]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.41
    Notes
    [72] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 14.
    Statistical analysis title
    Crisaborole QD:6-11yrs Vs Crisaborole BID:6-11yrs
    Statistical analysis description
    Change at Day 15, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    Comparison groups
    Crisaborole 2% QD Sub-group: Age group 6 to 11 Years v Crisaborole 2% BID Sub-group: Age group 6 to 11 years
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39

    Secondary: 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

    Close Top of page
    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
    End point values
    Crisaborole 2% QD: Age group 2 to 11 years Vehicle QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years Vehicle BID: Age group 2 to 11 years
    Number of subjects analysed
    20
    20
    20
    20
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline
    4.7 ± 0.56
    5.0 ± 0.50
    5.5 ± 0.56
    5.1 ± 0.56
        Change at Day 2
    -0.5 ± 0.30
    -0.4 ± 0.31
    -0.7 ± 0.40
    -0.9 ± 0.50
        Change at Day 3
    -0.7 ± 0.28
    -0.5 ± 0.35
    -1.6 ± 0.47
    -1.3 ± 0.55
        Change at Day 4
    -0.5 ± 0.51
    -0.4 ± 0.38
    -1.8 ± 0.64
    -1.6 ± 0.58
        Change at Day 5
    -1.4 ± 0.48
    -0.1 ± 0.60
    -2.0 ± 0.66
    -2.1 ± 0.52
        Change at Day 6
    -1.9 ± 0.45
    -0.9 ± 0.43
    -2.7 ± 0.62
    -2.2 ± 0.66
        Change at Day 7
    -2.0 ± 0.40
    -0.9 ± 0.45
    -3.0 ± 0.64
    -1.9 ± 0.71
        Change at Day 8
    -2.3 ± 0.41
    -1.3 ± 0.36
    -3.3 ± 0.66
    -2.0 ± 0.70
        Change at Day 9
    -2.0 ± 0.50
    -0.8 ± 0.42
    -3.4 ± 0.61
    -2.5 ± 0.63
        Change at Day 10
    -2.2 ± 0.39
    -0.9 ± 0.42
    -3.9 ± 0.62
    -2.3 ± 0.65
        Change at Day 11
    -2.4 ± 0.43
    -1.1 ± 0.45
    -3.5 ± 0.69
    -2.4 ± 0.66
        Change at Day 12
    -2.1 ± 0.45
    -0.7 ± 0.61
    -4.1 ± 0.60
    -2.5 ± 0.65
        Change at Day 13
    -2.1 ± 0.55
    -1.0 ± 0.50
    -4.1 ± 0.54
    -2.6 ± 0.70
        Change at Day 14
    -2.4 ± 0.48
    -1.2 ± 0.49
    -4.3 ± 0.56
    -2.8 ± 0.66
        Change at Day 15
    -2.5 ± 0.55
    -1.3 ± 0.45
    -4.3 ± 0.63
    -3.0 ± 0.61
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 2, Intra-subject: 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
    Pre-specified
    Analysis type
    other [73]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [73] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 2, Intra-subject: 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
    Pre-specified
    Analysis type
    other [74]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Notes
    [74] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 2, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 3, Intra-subject: 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
    Pre-specified
    Analysis type
    other [75]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Notes
    [75] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 3, Intra-subject: 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
    Pre-specified
    Analysis type
    other [76]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Notes
    [76] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 3, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 4, Intra-subject: 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
    Pre-specified
    Analysis type
    other [77]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [77] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 4, Intra-subject: 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
    Pre-specified
    Analysis type
    other [78]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    1.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Notes
    [78] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 4, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.74
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 5, Intra-subject: 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
    Pre-specified
    Analysis type
    other [79]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Notes
    [79] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 5, Intra-subject: 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
    Pre-specified
    Analysis type
    other [80]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Notes
    [80] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 5, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.7
         upper limit
    1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 6, Intra-subject: 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
    Pre-specified
    Analysis type
    other [81]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [81] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 6, Intra-subject: 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
    Pre-specified
    Analysis type
    other [82]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.47
    Notes
    [82] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 6, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.7
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.63
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 7, Intra-subject: 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
    Pre-specified
    Analysis type
    other [83]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [83] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 7, Intra-subject: 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
    Pre-specified
    Analysis type
    other [84]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.1
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Notes
    [84] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 7, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [85]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [85] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 8, Intra-subject: 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
    Pre-specified
    Analysis type
    other [86]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52
    Notes
    [86] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 8, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.64
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 9, Intra-subject: 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
    Pre-specified
    Analysis type
    other [87]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.3
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [87] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 9, Intra-subject: 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
    Pre-specified
    Analysis type
    other [88]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Notes
    [88] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 9, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.63
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 10, Intra-subject: 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
    Pre-specified
    Analysis type
    other [89]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [89] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 10, Intra-subject: 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
    Pre-specified
    Analysis type
    other [90]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [90] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 10, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.6
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.58
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 11, Intra-subject: 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
    Pre-specified
    Analysis type
    other [91]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Notes
    [91] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 11, Intra-subject: 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
    Pre-specified
    Analysis type
    other [92]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Notes
    [92] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 11, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.67
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 12, Intra-subject: 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
    Pre-specified
    Analysis type
    other [93]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Notes
    [93] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 12, Intra-subject: 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
    Pre-specified
    Analysis type
    other [94]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Notes
    [94] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 12, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.63
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 13, Intra-subject: 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
    Pre-specified
    Analysis type
    other [95]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Notes
    [95] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 13, Intra-subject: 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
    Pre-specified
    Analysis type
    other [96]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Notes
    [96] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 13, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 14, Intra-subject: 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
    Pre-specified
    Analysis type
    other [97]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    -0.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45
    Notes
    [97] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 14, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    -0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.59
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 14, Intra-subject: 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
    Pre-specified
    Analysis type
    other [98]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Notes
    [98] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD: 2-11yrs Vs Vehicle QD: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    other [99]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Notes
    [99] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole BID: 2-11yrs Vs Vehicle BID: 2-11yrs
    Statistical analysis description
    Change at Day 15, Intra-subject: 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
    Pre-specified
    Analysis type
    other [100]
    Method
    Parameter type
    Least squares mean of difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46
    Notes
    [100] - This was an intra-subject comparison. Hence the actual number of subjects involved in the analysis was 20.
    Statistical analysis title
    Crisaborole QD:2-11yrs Vs Crisaborole BID:2-11yrs
    Statistical analysis description
    Change at Day 15, Inter-subject: Mixed effect model for repeated measures included the fixed effects of dosing regimen day dosing regimen-by-day interaction and baseline value and the covariance structure UN was used.
    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
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Difference of least squares mean
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) in the Target Lesions per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term

    Close Top of page
    End point title
    Number of Subjects With Treatment-Emergent 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. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. For this endpoint, treatment-emergent 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)
    End point values
    Crisaborole 2% QD: Age group >=12 years Vehicle QD: Age group >=12 years Crisaborole 2% BID: Age group >=12 years Vehicle BID: Age group >=12 years Crisaborole 2% QD: Age group 2 to 11 years Vehicle QD: Age group 2 to 11 years Crisaborole 2% BID: Age group 2 to 11 years Vehicle BID: Age group 2 to 11 years Crisaborole 2% QD: All age group Vehicle QD: All age group Crisaborole 2% BID: All age group Vehicle BID: All age group
    Number of subjects analysed
    20
    20
    21
    21
    20
    20
    20
    20
    40
    40
    41
    41
    Units: subjects
        Application site coldness
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
        Application site irritation
    2
    1
    4
    1
    0
    0
    0
    0
    2
    1
    4
    1
        Application site pain
    1
    0
    1
    0
    0
    0
    1
    0
    1
    0
    2
    0
        Application site pruritus
    2
    2
    1
    1
    0
    0
    1
    0
    2
    2
    2
    1
        Application site folliculitis
    1
    0
    1
    0
    0
    0
    0
    0
    1
    0
    1
    0
    No statistical analyses for this end point

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

    Close Top of page
    End point title
    Number of Subjects With Treatment-Emergent 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. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. Safety analysis set included all 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)
    End point values
    Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 2-11 years Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 2-11 years
    Number of subjects analysed
    20
    21
    20
    20
    Units: subjects
        Subjects With AEs
    6
    6
    2
    2
        Subjects With SAEs
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    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
    Non-systematic
    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 (intra-subject) 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 (intra-subject) 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 2-11 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 (intra-subject) 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 2-11 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 (intra-subject) for 15 days and subjects were followed up to maximum of 35 days after the end of treatment (maximum up to Day 50).

    Serious adverse events
    Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 2-11 years Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 2-11 years
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Cohort 1: Crisaborole 2% QD + Vehicle QD, Age group >=12 years Cohort 1:Crisaborole 2% BID + Vehicle BID,Age group >=12 years Cohort 2:Crisaborole 2% QD + Vehicle QD, Age group 2-11 years Cohort 2:Crisaborole 2% BID + Vehicle BID,Age group 2-11 years
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 20 (30.00%)
    6 / 21 (28.57%)
    2 / 20 (10.00%)
    2 / 20 (10.00%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    3
    0
    0
    General disorders and administration site conditions
    Application site coldness
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Application site irritation
         subjects affected / exposed
    3 / 20 (15.00%)
    4 / 21 (19.05%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    3
    4
    0
    0
    Application site pain
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    0
    1
    Application site pruritus
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    3
    2
    0
    1
    Gastrointestinal disorders
    Dental caries
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Application site folliculitis
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    0
    1
    1

    More information

    Close Top of page

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA