A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD

• ClinicalTrials.gov Identifier: NCT03539601
• Recruitment Status: Terminated
• First Posted: May 29, 2018
• Results First Posted: January 10, 2022
• Last Update Posted: January 10, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis
• Interventions: Drug: Crisaborole ointment, 2%; Drug: Hydrocortisone butyrate cream, 0.1%; Drug: Pimecrolimus cream, 1%; Drug: Crisaborole Vehicle
• Enrollment: 237

Participant Flow

Recruitment Details	At time of early termination, less than 40% of planned participants were treated across treatment groups. Number of participants enrolled up to early termination of study were insufficient to allow a meaningful inference and robust statistical analyses of data. As a result, all safety data was summarized with Cohort 1 and Cohort 2 combined for crisaborole and vehicle groups.
Pre-assignment Details	This study was originally plan to conduct in 2 different cohorts for crisaborole and vehicle groups. Cohort 1 was planned for participants eligible for topical corticosteroid (TCS) therapy (hydrocortisone butyrate cream 0.1%), and Cohort 2 was planned for participants not eligible for TCS therapy but eligible for topical calcineurin inhibitor (TCI) therapy (pimecrolimus cream 1%).

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description	Vehicle matched to crisaborole 2% ointment was applied topically bis in diem (BID - twice a day) to all treatable atopic dermatitis (AD) involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Period Title: Overall Study
Started	60	59	71	47
Treated	59	58	71	47
Completed	54	52	65	46
Not Completed	6	7	6	1
Reason Not Completed
Withdraw by parent/guardian	1	0	1	0
Adverse Event	0	2	0	0
Lost to Follow-up	2	4	5	0
Withdrawal by Subject	2	0	0	1
Randomized but not treated	1	1	0	0

Baseline Characteristics

Arm/Group Title		Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID	Total
Arm/Group Description		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Total of all reporting groups
Overall Number of Baseline Participants		59	58	71	47	235
Baseline Analysis Population Description		Full analysis set (FAS) included all randomized participants received at least 1 dose of investigational product.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	59 participants	58 participants	71 participants	47 participants	235 participants
		19.8 (18.22)	21.5 (19.12)	19.6 (16.28)	21.1 (18.20)	20.4 (17.79)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	58 participants	71 participants	47 participants	235 participants
	Female	35 59.3%	35 60.3%	43 60.6%	26 55.3%	139 59.1%
	Male	24 40.7%	23 39.7%	28 39.4%	21 44.7%	96 40.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	58 participants	71 participants	47 participants	235 participants
	Hispanic or Latino	6 10.2%	1 1.7%	11 15.5%	4 8.5%	22 9.4%
	Not Hispanic or Latino	53 89.8%	57 98.3%	60 84.5%	43 91.5%	213 90.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	58 participants	71 participants	47 participants	235 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	2 3.4%	3 5.2%	1 1.4%	3 6.4%	9 3.8%
	Native Hawaiian or Other Pacific Islander	1 1.7%	0 0.0%	0 0.0%	0 0.0%	1 0.4%
	Black or African American	17 28.8%	14 24.1%	23 32.4%	6 12.8%	60 25.5%
	White	38 64.4%	38 65.5%	44 62.0%	37 78.7%	157 66.8%
	More than one race	1 1.7%	3 5.2%	1 1.4%	0 0.0%	5 2.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	2 2.8%	1 2.1%	3 1.3%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in the Eczema Area and Severity Index (EASI) Total Score at Day 29
Description	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and percent (%) body surface area (%BSA) affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Time Frame	Baseline, Day 29

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

Arm/Group Title	Vehicle: Participants 2-17 Years	Crisaborole Ointment 2% BID: Participants 2-17 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants 2-17 Years	Pimecrolimus Cream 1% BID: Participants 2-17 Years	Vehicle: Participants >=18 Years	Crisaborole Ointment 2% BID: Participants >=18 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants >=18 Years	Pimecrolimus Cream 1% BID: Participants >=18 Years
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	31	31	36	29	17	19	29	14
Mean (Standard Deviation); Unit of Measure: Percent change
	-26.62 (46.283)	-49.47 (34.195)	-75.50 (30.305)	-60.08 (31.877)	-44.67 (49.267)	-57.14 (48.345)	-70.29 (32.097)	-62.59 (28.317)

2. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Discontinuations Due to AEs and SAEs
Description	An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs are events between the first dose of study drug up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A SAE is any untoward medical occurrence at any dose that: results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event.
Time Frame	From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	71	47
Measure Type: Count of Participants; Unit of Measure: Participants
TEAEs	18 30.5%	25 43.1%	12 16.9%	24 51.1%
SAEs	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Discontinuation due to AEs	0 0.0%	3 5.2%	0 0.0%	0 0.0%
Discontinuation due to SAEs	0 0.0%	0 0.0%	0 0.0%	0 0.0%

3. Primary Outcome

Title	Number of Participants With Local Tolerability Adverse Events (AEs)
Description	Local tolerability AEs included application and instillation site reactions, application site discharge, application site erythema, application site exfoliation, application site pain, application site pruritus, application site swelling, dermatitis and eczema, dermatitis atopic, dermatitis contact, eczema, skin irritation, telangiectasia and related conditions, and urticarias.
Time Frame	From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	71	47
Measure Type: Count of Participants; Unit of Measure: Participants
	12 20.3%	13 22.4%	2 2.8%	8 17.0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Changes in Vital Signs
Description	Vital sign measurements included temperature, respiratory rate, pulse rate, and blood pressure. Temperature, respiratory rate, pulse rate, and blood pressure were taken in the seated or supine position, after the participant has been sitting or lying calmly for a minimum of 5 minutes (when possible for younger children). Position of recording was consistent within participant through-out the study.
Time Frame	Screening up to Day 29

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	71	47
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	1 1.4%	0 0.0%

5. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Description	Hematology parameters included with criteria greater than (>) 1.2*upper limit of normal (ULN): leukocytes (10^3 per cubic millimeter [10^3/mm^3]), lymphocytes (10^3/mm^3), lymphocytes/leukocytes (%), neutrophils (10^3/mm^3), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils (10^3/mm^3), eosinophils/leukocytes (%), monocytes (10^3/mm^3), monocytes/leukocytes (%). Clinical chemistry included parameters: aspartate aminotransferase (units per liter [U/L]) (>3.0* ULN), alanine aminotransferase (U/L) (>3.0* ULN), alkaline phosphatase (U/L) (>3.0* ULN), creatinine (milligram per deciliter [mg/dL]) (>1.3* ULN), potassium (milliequivalent per liter [mEq/L]) (>1.1* ULN), bicarbonate (mEq/L) (>1.1* ULN).
Time Frame	Screening up to Day 29

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	71	47
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	1 1.4%	0 0.0%

6. Secondary Outcome

Title	Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15 and 22
Description	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Time Frame	Baseline, Day 8, 15 and 22

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product. Here, 'number analyzed' signifies number of participants evaluable for each specified row.

Arm/Group Title		Vehicle: Participants 2-17 Years	Crisaborole Ointment 2% BID: Participants 2-17 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants 2-17 Years	Pimecrolimus Cream 1% BID: Participants 2-17 Years	Vehicle: Participants >=18 Years	Crisaborole Ointment 2% BID: Participants >=18 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants >=18 Years	Pimecrolimus Cream 1% BID: Participants >=18 Years
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		38	37	38	30	21	21	32	17
Mean (Standard Deviation); Unit of Measure: Percent change
Percent Change at Day 8	Number Analyzed	37 participants	33 participants	33 participants	29 participants	19 participants	21 participants	27 participants	16 participants
		-17.88 (36.705)	-26.79 (39.280)	-45.59 (28.103)	-34.20 (25.972)	-14.77 (26.308)	-29.83 (44.599)	-42.48 (27.843)	-18.75 (39.016)
Percent Change at Day 15	Number Analyzed	33 participants	33 participants	37 participants	30 participants	15 participants	20 participants	27 participants	14 participants
		-25.77 (35.658)	-36.72 (36.625)	-58.96 (32.617)	-42.75 (31.854)	-25.93 (31.690)	-48.42 (33.458)	-56.29 (32.186)	-37.18 (50.487)
Percent Change at Day 22	Number Analyzed	32 participants	31 participants	35 participants	26 participants	18 participants	19 participants	27 participants	15 participants
		-25.07 (49.326)	-38.87 (32.624)	-69.09 (31.528)	-59.86 (24.835)	-34.43 (30.587)	-56.05 (38.934)	-61.82 (27.894)	-42.25 (40.192)

7. Secondary Outcome

Title	Number of Participants Who Achieved Success in the Investigator's Static Global Assessment (ISGA) (ISGA Score of Clear [0] or Almost Clear [1] With At-least a 2-Grade Improvement From Baseline) at Day 8, 15, 22 and 29
Description	ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0= clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product.

Arm/Group Title	Vehicle: Participants 2-17 Years	Crisaborole Ointment 2% BID: Participants 2-17 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants 2-17 Years	Pimecrolimus Cream 1% BID: Participants 2-17 Years	Vehicle: Participants >=18 Years	Crisaborole Ointment 2% BID: Participants >=18 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants >=18 Years	Pimecrolimus Cream 1% BID: Participants >=18 Years
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	38	37	39	30	21	21	32	17
Measure Type: Count of Participants; Unit of Measure: Participants
Day 8	2 5.3%	0 0.0%	2 5.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Day 15	1 2.6%	3 8.1%	8 20.5%	2 6.7%	0 0.0%	0 0.0%	6 18.8%	1 5.9%
Day 22	2 5.3%	2 5.4%	11 28.2%	5 16.7%	1 4.8%	3 14.3%	9 28.1%	1 5.9%
Day 29	2 5.3%	5 13.5%	20 51.3%	7 23.3%	3 14.3%	6 28.6%	13 40.6%	2 11.8%

8. Secondary Outcome

Title	Number of Participants Who Achieved Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 8, 15, 22 and 29
Description	ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product.

Arm/Group Title	Vehicle: Participants 2-17 Years	Crisaborole Ointment 2% BID: Participants 2-17 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants 2-17 Years	Pimecrolimus Cream 1% BID: Participants 2-17 Years	Vehicle: Participants >=18 Years	Crisaborole Ointment 2% BID: Participants >=18 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants >=18 Years	Pimecrolimus Cream 1% BID: Participants >=18 Years
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	38	37	39	30	21	21	32	17
Measure Type: Count of Participants; Unit of Measure: Participants
Day 8	6 15.8%	3 8.1%	12 30.8%	5 16.7%	0 0.0%	4 19.0%	4 12.5%	2 11.8%
Day 15	6 15.8%	7 18.9%	19 48.7%	9 30.0%	1 4.8%	3 14.3%	11 34.4%	5 29.4%
Day 22	6 15.8%	8 21.6%	19 48.7%	9 30.0%	1 4.8%	8 38.1%	13 40.6%	5 29.4%
Day 29	6 15.8%	10 27.0%	27 69.2%	13 43.3%	4 19.0%	9 42.9%	20 62.5%	7 41.2%

9. Secondary Outcome

Title	Number of Participants Who Achieved Greater Than or Equal to (>=) 75 Percent (%) Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15, 22 and 29
Description	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	70	47
Measure Type: Count of Participants; Unit of Measure: Participants
Day 8	2 3.4%	7 12.1%	9 12.9%	2 4.3%
Day 15	4 6.8%	10 17.2%	25 35.7%	8 17.0%
Day 22	8 13.6%	13 22.4%	29 41.4%	11 23.4%
Day 29	9 15.3%	17 29.3%	40 57.1%	17 36.2%

10. Secondary Outcome

Title	Time to First Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score of Greater Than or Equal to (>=) 75%
Description	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Time Frame	Baseline up to Day 43

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	59	58	70	47
Median (95% Confidence Interval); Unit of Measure: Days
	NA [1]; (NA to NA)	43.0 [2]; (28.0 to NA)	23.0; (16.0 to 34.0)	32.0 [2]; (27.0 to NA)

[1]

Median and 95% CI could not be estimated because there were insufficient number of participants with event.

[2]

Upper limit for 95% CI could not be estimated because there were insufficient number of participants with events to calculate the full 95% CI.

11. Secondary Outcome

Title	Change From Baseline in Percent Body Surface Area (%BSA) at Day 8, 15, 22 and 29
Description	Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae) and lower limbs (including buttocks) excluding scalp. BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were: 10 for head, neck (20 for <8 years age), 20 for upper limbs, 30 for trunk, 40 for lower limbs (30 for <8 years age). Surface area (SA) of body region equivalent to 1 handprint: 10% for head, neck (5% for <8 years age), 5% for upper limbs, 3.33% for trunk, 2.5% for lower limbs (3.33% for <8 years age). Overall %BSA for a body region = total number of handprints in a body region * % SA equivalent to 1 handprint. % BSA for an individual: mean of % BSA of all 4 body regions, range =0-100%, higher values = greater AD severity.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of investigational product. Here 'number analyzed' signifies number of participants evaluable for each specified row.

Arm/Group Title		Vehicle: Participants 2-17 Years	Crisaborole Ointment 2% BID: Participants 2-17 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants 2-17 Years	Pimecrolimus Cream 1% BID: Participants 2-17 Years	Vehicle: Participants >=18 Years	Crisaborole Ointment 2% BID: Participants >=18 Years	Hydrocortisone Butyrate Cream 0.1% BID: Participants >=18 Years	Pimecrolimus Cream 1% BID: Participants >=18 Years
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		38	37	39	30	21	21	32	17
Mean (Standard Deviation); Unit of Measure: Percent BSA
Change at Day 8	Number Analyzed	37 participants	33 participants	33 participants	29 participants	19 participants	21 participants	27 participants	16 participants
		-2.04 (7.533)	-2.63 (11.920)	-5.25 (8.346)	-2.84 (5.296)	-1.39 (4.417)	-4.09 (6.397)	-2.74 (2.718)	-1.44 (5.600)
Change at Day 15	Number Analyzed	33 participants	33 participants	37 participants	30 participants	15 participants	20 participants	27 participants	14 participants
		-2.38 (8.566)	-4.32 (12.620)	-7.40 (9.515)	-3.72 (4.401)	-3.73 (5.895)	-4.63 (7.211)	-5.00 (5.189)	-3.56 (5.750)
Change at Day 22	Number Analyzed	32 participants	31 participants	35 participants	26 participants	18 participants	19 participants	27 participants	15 participants
		-2.23 (12.321)	-7.14 (10.123)	-8.54 (11.226)	-6.52 (9.883)	-4.19 (5.464)	-5.98 (7.852)	-4.91 (5.190)	-4.17 (5.588)
Change at Day 29	Number Analyzed	31 participants	31 participants	36 participants	29 participants	17 participants	19 participants	29 participants	14 participants
		-3.38 (9.974)	-9.95 (11.324)	-9.63 (12.309)	-7.30 (10.774)	-6.76 (8.089)	-7.18 (8.183)	-7.18 (5.971)	-6.86 (8.172)

12. Secondary Outcome

Title	Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged >=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.

Arm/Group Title		Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		33	33	45	28
Mean (Standard Deviation); Unit of Measure: Units on a scale
Change at Day 8	Number Analyzed	30 participants	30 participants	43 participants	26 participants
		-0.67 (1.254)	-1.01 (1.145)	-2.24 (2.065)	-0.29 (1.225)
Change at Day 15	Number Analyzed	29 participants	32 participants	43 participants	25 participants
		-0.97 (1.778)	-1.08 (1.419)	-3.21 (2.598)	-1.35 (1.707)
Change at Day 22	Number Analyzed	27 participants	30 participants	42 participants	24 participants
		-0.98 (1.887)	-1.28 (1.642)	-3.83 (2.554)	-1.66 (1.759)
Change at Day 29	Number Analyzed	27 participants	29 participants	42 participants	24 participants
		-1.30 (2.157)	-1.65 (1.996)	-4.02 (2.734)	-1.67 (1.952)

13. Secondary Outcome

Title	Change From Baseline in Participant Reported Itch Severity Scale in Participants Aged 6-11 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the five-category participant reported itch severity scale for participants aged 6-11 years. Participants at specified time points were asked to "circle the face that shows how itchy your skin has been today". The scale ranged from 0 to 4, where 0= no itch and 4= very itch. Higher scores indicated worse itch.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

14. Secondary Outcome

Title	Change From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the participant reported itch severity scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

15. Secondary Outcome

Title	Time to Greater Than or Equal to (>=2) Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>) 12 Years
Description	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline up to Day 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflected limitations related to reduced sample size (only 39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Summarizing further by Time to >2 Point Improvement will not provide additional useful information due to smaller than planned sample size as a result of study early termination.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

16. Secondary Outcome

Title	Time to >= 3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>)12 Years
Description	The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged >12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline up to Day 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflected limitations related to reduced sample size (only 39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Summarizing further by Time to >3 Point Improvement will not provide additional useful information due to smaller than planned sample size as a result of study early termination.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

17. Secondary Outcome

Title	Time >=2 Point to Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years
Description	The severity of itch (pruritus) due to AD was assessed using the patient reported itch severity scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline up to Day 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

18. Secondary Outcome

Title	Time to >=3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years
Description	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Baseline up to Day 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

19. Secondary Outcome

Title	Number of Participants Who Achieved >=2 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged >=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	31	32	42	26
Measure Type: Count of Participants; Unit of Measure: Participants
Day 8	3 9.7%	7 21.9%	21 50.0%	1 3.8%
Day 15	9 29.0%	8 25.0%	31 73.8%	7 26.9%
Day 22	9 29.0%	7 21.9%	32 76.2%	9 34.6%
Day 29	10 32.3%	9 28.1%	32 76.2%	9 34.6%

20. Secondary Outcome

Title	Number of Participants Who Achieved >=3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged >=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	29	29	40	26
Measure Type: Count of Participants; Unit of Measure: Participants
Day 8	2 6.9%	1 3.4%	11 27.5%	0 0.0%
Day 15	5 17.2%	5 17.2%	21 52.5%	3 11.5%
Day 22	4 13.8%	4 13.8%	25 62.5%	4 15.4%
Day 29	6 20.7%	6 20.7%	24 60.0%	6 23.1%

21. Secondary Outcome

Title	Number of Participants Who Achieved Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

22. Secondary Outcome

Title	Number of Participants Who Achieved Greater Than or Equal to (>=) 3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29
Description	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time Frame	Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

23. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) in Participants Greater Than or Equal to (>=) 16 Years at Day 8, 15, 22 and 29
Description	DLQI is a 10-item questionnaire that measures the impact of skin disease on participants aged >=16 years. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participant.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged >=16 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.

Arm/Group Title		Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		23	26	32	23
Mean (Standard Deviation); Unit of Measure: Units on a scale
Change at Day 8	Number Analyzed	20 participants	23 participants	27 participants	19 participants
		-1.9 (5.53)	-3.8 (3.45)	-5.1 (4.98)	-1.4 (2.99)
Change at Day 15	Number Analyzed	16 participants	23 participants	26 participants	17 participants
		-3.4 (3.72)	-3.5 (2.92)	-6.8 (5.94)	-2.9 (2.63)
Change at Day 22	Number Analyzed	18 participants	20 participants	25 participants	18 participants
		-2.8 (4.12)	-3.4 (4.73)	-6.9 (6.37)	-3.4 (3.88)
Change at Day 29	Number Analyzed	18 participants	19 participants	28 participants	17 participants
		-4.9 (5.60)	-3.9 (4.76)	-7.0 (6.69)	-4.1 (3.76)

24. Secondary Outcome

Title	Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) in Participants Aged 4-15 Years at Day 8, 15, 22 and 29
Description	The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4 to 15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranged from 0 (not at all) to 30 (very much): 0-1 = no effect on the child's life; 2-6 = small effect; 7-12 = moderate effect; 13-18 = very large effect; 19-30 = extremely large effect. Higher scores indicated more impact on quality of life of children.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged 4 to 15 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure and 'number analyzed' = participants evaluable for each specified row.

Arm/Group Title		Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		27	26	30	18
Mean (Standard Deviation); Unit of Measure: Units on a scale
Change at Day 8	Number Analyzed	27 participants	22 participants	25 participants	15 participants
		-0.2 (3.42)	-2.1 (4.49)	-5.4 (6.14)	-1.7 (4.03)
Change at Day 15	Number Analyzed	22 participants	24 participants	29 participants	17 participants
		-2.0 (4.49)	-3.1 (5.13)	-5.5 (6.32)	-1.6 (4.66)
Change at Day 22	Number Analyzed	21 participants	21 participants	27 participants	13 participants
		-2.7 (3.04)	-2.6 (5.81)	-4.9 (7.89)	-2.5 (3.15)
Change at Day 29	Number Analyzed	20 participants	21 participants	28 participants	16 participants
		-3.1 (2.73)	-3.4 (4.85)	-6.4 (5.49)	-3.4 (3.52)

25. Secondary Outcome

Title	Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) in Participants Aged 2-17 Years at Day 8, 15, 22 and 29
Description	The DFI was a 10-item disease questionnaire that measures the impact of having a child (aged 2-17 years) with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (not at all) to 30 (very much): where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranged from 0 (no impact on life of family) to 30 (maximum effect on life of family), where higher DFI scores indicated maximum effect on life of family.
Time Frame	Baseline, Day 8, 15, 22 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants aged 2 to 17 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure and 'number analyzed' = participants evaluable for each specified row.

Arm/Group Title		Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description:		Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
Overall Number of Participants Analyzed		38	37	39	30
Mean (Standard Deviation); Unit of Measure: Units on a scale
Change at Day 8	Number Analyzed	37 participants	32 participants	33 participants	28 participants
		-1.2 (6.43)	-2.3 (5.16)	-5.6 (5.61)	-2.8 (6.79)
Change at Day 15	Number Analyzed	32 participants	31 participants	37 participants	30 participants
		-1.1 (6.77)	-2.3 (4.71)	-5.5 (6.82)	-3.2 (5.94)
Change at Day 22	Number Analyzed	31 participants	29 participants	34 participants	26 participants
		-2.5 (4.84)	-3.1 (5.24)	-5.3 (6.92)	-4.5 (5.93)
Change at Day 29	Number Analyzed	30 participants	28 participants	35 participants	29 participants
		-1.8 (5.26)	-3.6 (4.40)	-6.4 (5.61)	-4.8 (5.61)

Adverse Events

Time Frame	Day 1 up to 28 days after last dose of study treatment (maximum up to 60 days)
Adverse Event Reporting Description	Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.
Arm/Group Title	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
Arm/Group Description	Vehicle matched to crisaborole 2% ointment was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Crisaborole ointment 2% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Hydrocortisone butyrate cream 0.1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.	Pimecrolimus cream 1% was applied topically BID to all treatable AD involved areas (excluding the scalp) identified at Baseline (Day 1) through Day 28. End of treatment visit was scheduled on Day 29. Participants were followed-up for at least 28 days after last dose, maximum up to Day 60.
All-Cause Mortality
	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/59 (0.00%)	0/58 (0.00%)	0/71 (0.00%)	0/47 (0.00%)
Serious Adverse Events
	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/59 (0.00%)	0/58 (0.00%)	0/71 (0.00%)	0/47 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Vehicle	Crisaborole Ointment 2% BID	Hydrocortisone Butyrate Cream 0.1% BID	Pimecrolimus Cream 1% BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/59 (16.95%)	18/58 (31.03%)	4/71 (5.63%)	16/47 (34.04%)
General disorders
Application site pain * 1	1/59 (1.69%)	8/58 (13.79%)	0/71 (0.00%)	2/47 (4.26%)
Infections and infestations
Nasopharyngitis * 1	2/59 (3.39%)	3/58 (5.17%)	0/71 (0.00%)	3/47 (6.38%)
Rhinitis * 1	0/59 (0.00%)	2/58 (3.45%)	1/71 (1.41%)	3/47 (6.38%)
Nervous system disorders
Headache * 1	1/59 (1.69%)	3/58 (5.17%)	2/71 (2.82%)	2/47 (4.26%)
Skin and subcutaneous tissue disorders
Dermatitis atopic * 1	7/59 (11.86%)	4/58 (6.90%)	2/71 (2.82%)	7/47 (14.89%)
Eczema * 1	0/59 (0.00%)	3/58 (5.17%)	0/71 (0.00%)	1/47 (2.13%)
1 Term from vocabulary, MedDRA 23.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

Study was terminated early by sponsor. Decision was not due to safety/efficacy concerns, but was related to business, portfolio reprioritization. Sub-study planned as per Amendment 3 was not initiated, as sub study site setup didn't complete prior to study termination.

More Information

Certain Agreements

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

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

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

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 18007181021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03539601
• Other Study ID Numbers: C3291037; 2018-001043-31 ( EudraCT Number )
• First Submitted: May 16, 2018
• First Posted: May 29, 2018
• Results First Submitted: December 8, 2021
• Results First Posted: January 10, 2022
• Last Update Posted: January 10, 2022