Trial Outcomes & Findings for Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis (NCT NCT03233529)

NCT ID: NCT03233529

Last Updated: 2019-08-13

Results Overview

The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: Baseline (Day 1), Day 15
• Results posted on: 2019-08-13

Participant Flow

Participant milestones

Measure	Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2% The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42.
Double-Blind Period (Day 1 to Day 15) STARTED	40
Double-Blind Period (Day 1 to Day 15) COMPLETED	39
Double-Blind Period (Day 1 to Day 15) NOT COMPLETED	1
Open-Label Period (Day 15 to Day 71) STARTED	39
Open-Label Period (Day 15 to Day 71) COMPLETED	38
Open-Label Period (Day 15 to Day 71) NOT COMPLETED	1

Reasons for withdrawal

Measure	Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2% The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42.
Double-Blind Period (Day 1 to Day 15) Adverse Event	1
Open-Label Period (Day 15 to Day 71) Adverse Event	1

Baseline Characteristics

Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis

Baseline characteristics by cohort

Measure	Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2% n=40 Participants The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42.
Age, Continuous	32.2 years STANDARD_DEVIATION 11.29 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15.

The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-4.5 units on a scale Standard Error 0.31	-2.1 units on a scale Standard Error 0.35

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-1.2787 log2(normalized expression) Standard Error 0.36339	-0.2881 log2(normalized expression) Standard Error 0.34055

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.7295 log2(normalized expression) Standard Error 0.25784	-0.1849 log2(normalized expression) Standard Error 0.25272

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-1.3267 log2(normalized expression) Standard Error 0.24359	-0.1994 log2(normalized expression) Standard Error 0.22335

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.5484 log2(normalized expression) Standard Error 0.25767	0.2128 log2(normalized expression) Standard Error 0.27893

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-2.4495 log2(normalized expression) Standard Error 0.30229	-1.0854 log2(normalized expression) Standard Error 0.33131

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-2.4235 log2(normalized expression) Standard Error 0.33463	-1.2989 log2(normalized expression) Standard Error 0.35218

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-3.2762 log2(normalized expression) Standard Error 0.39686	-1.2849 log2(normalized expression) Standard Error 0.40613

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.2737 log2-scale micrometers Standard Error 0.10653	-0.1779 log2-scale micrometers Standard Error 0.08229

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CD11c	-0.4736 log2-scale cells per square millimeter Standard Error 0.18946	-0.1694 log2-scale cells per square millimeter Standard Error 0.11081
Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CD3	-0.6219 log2-scale cells per square millimeter Standard Error 0.15152	-0.2642 log2-scale cells per square millimeter Standard Error 0.13959
Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 FceR1	-0.4226 log2-scale cells per square millimeter Standard Error 0.16068	-0.1314 log2-scale cells per square millimeter Standard Error 0.16513
Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 Ki67	-1.0983 log2-scale cells per square millimeter Standard Error 0.21512	-0.8971 log2-scale cells per square millimeter Standard Error 0.19918
Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 Langerin	0.3694 log2-scale cells per square millimeter Standard Error 0.27896	0.2779 log2-scale cells per square millimeter Standard Error 0.19645

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-32	-0.2992 log2(normalized expression) Standard Error 0.16762	0.1878 log2(normalized expression) Standard Error 0.15632
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CCL13	-0.3095 log2(normalized expression) Standard Error 0.21520	0.0604 log2(normalized expression) Standard Error 0.20967
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CCL20	-0.2016 log2(normalized expression) Standard Error 0.23629	0.1088 log2(normalized expression) Standard Error 0.23212
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CCL26	0.0231 log2(normalized expression) Standard Error 0.18602	0.1195 log2(normalized expression) Standard Error 0.22820
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CRLF2	-0.8058 log2(normalized expression) Standard Error 0.13728	-0.2023 log2(normalized expression) Standard Error 0.14431
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CXCL1	-1.4174 log2(normalized expression) Standard Error 0.23956	0.1924 log2(normalized expression) Standard Error 0.32423
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CXCL10	-1.0779 log2(normalized expression) Standard Error 0.36531	0.6697 log2(normalized expression) Standard Error 0.37822
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CXCL2	-0.5462 log2(normalized expression) Standard Error 0.21129	0.1945 log2(normalized expression) Standard Error 0.20700
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 CXCL9	-0.9941 log2(normalized expression) Standard Error 0.33692	0.7562 log2(normalized expression) Standard Error 0.39811
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 DEFB4A	-3.5331 log2(normalized expression) Standard Error 0.42635	-1.3456 log2(normalized expression) Standard Error 0.46988
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 FLG	-0.2155 log2(normalized expression) Standard Error 0.18503	-0.3670 log2(normalized expression) Standard Error 0.22285
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 FOXP3	-0.5115 log2(normalized expression) Standard Error 0.12709	-0.0273 log2(normalized expression) Standard Error 0.16057
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IFNG	-0.5588 log2(normalized expression) Standard Error 0.34472	0.5737 log2(normalized expression) Standard Error 0.31138
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-10	-0.3773 log2(normalized expression) Standard Error 0.19458	0.2950 log2(normalized expression) Standard Error 0.17314
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-15	-0.2307 log2(normalized expression) Standard Error 0.12331	0.2193 log2(normalized expression) Standard Error 0.11761
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-15RA	-0.0780 log2(normalized expression) Standard Error 0.10814	0.2110 log2(normalized expression) Standard Error 0.10624
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-17A	-1.1577 log2(normalized expression) Standard Error 0.57223	0.7516 log2(normalized expression) Standard Error 0.59970
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-17F	-1.9482 log2(normalized expression) Standard Error 0.79294	0.5309 log2(normalized expression) Standard Error 0.88038
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-19	-3.1946 log2(normalized expression) Standard Error 0.78012	-0.8108 log2(normalized expression) Standard Error 0.75460
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-1B	-0.5792 log2(normalized expression) Standard Error 0.21864	0.2808 log2(normalized expression) Standard Error 0.29124
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-2	-0.5352 log2(normalized expression) Standard Error 0.26229	0.2769 log2(normalized expression) Standard Error 0.16896
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-22	-1.4970 log2(normalized expression) Standard Error 0.39951	-0.0170 log2(normalized expression) Standard Error 0.35503
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-2RA	-0.8836 log2(normalized expression) Standard Error 0.19462	-0.0824 log2(normalized expression) Standard Error 0.22176
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-31	-1.5885 log2(normalized expression) Standard Error 0.60512	-0.3997 log2(normalized expression) Standard Error 0.65363
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-5	-0.3487 log2(normalized expression) Standard Error 0.51329	-0.4148 log2(normalized expression) Standard Error 0.42311
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-6	-0.8814 log2(normalized expression) Standard Error 0.32670	0.1724 log2(normalized expression) Standard Error 0.36369
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-8	-1.9805 log2(normalized expression) Standard Error 0.37922	-0.1698 log2(normalized expression) Standard Error 0.42603
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-9	-2.2803 log2(normalized expression) Standard Error 0.71683	-1.0530 log2(normalized expression) Standard Error 0.68305
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-12A	0.2787 log2(normalized expression) Standard Error 0.20557	0.5251 log2(normalized expression) Standard Error 0.16751
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 IL-23A	-1.2754 log2(normalized expression) Standard Error 0.26058	-0.1173 log2(normalized expression) Standard Error 0.28133
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 LOR	0.3759 log2(normalized expression) Standard Error 0.19707	-0.1041 log2(normalized expression) Standard Error 0.21965
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 MMP-12	-1.9588 log2(normalized expression) Standard Error 0.39817	-0.4205 log2(normalized expression) Standard Error 0.34033
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 PDE4A	0.0105 log2(normalized expression) Standard Error 0.12015	0.1359 log2(normalized expression) Standard Error 0.11153
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 PDE4B	-0.1900 log2(normalized expression) Standard Error 0.12061	0.1923 log2(normalized expression) Standard Error 0.10897
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 PDE4D	-0.3865 log2(normalized expression) Standard Error 0.12920	0.0736 log2(normalized expression) Standard Error 0.12231
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 PPL	-0.3000 log2(normalized expression) Standard Error 0.09781	-0.1933 log2(normalized expression) Standard Error 0.12180
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 RNA18SP5	0.1121 log2(normalized expression) Standard Error 0.08576	-0.0221 log2(normalized expression) Standard Error 0.06550
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 S100A7	-2.1764 log2(normalized expression) Standard Error 0.30729	-0.8782 log2(normalized expression) Standard Error 0.26498
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 S100A8	-2.4454 log2(normalized expression) Standard Error 0.36057	-1.0669 log2(normalized expression) Standard Error 0.33255
Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 S100A9	-2.6155 log2(normalized expression) Standard Error 0.35209	-1.2976 log2(normalized expression) Standard Error 0.33324

SECONDARY outcome

Timeframe: Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 No change	10 Participants	19 Participants
Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 Partial normalization	10 Participants	5 Participants
Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 Full normalization	12 Participants	4 Participants
Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 Worsening	7 Participants	11 Participants

SECONDARY outcome

Timeframe: Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Number of Participants With Categorical Histological Response at Day 15 Non-responder	18 Participants	30 Participants
Number of Participants With Categorical Histological Response at Day 15 Responder	21 Participants	9 Participants

SECONDARY outcome

Timeframe: Day 15

Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.

KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Number of Participants With Categorical KRT16 Expression at Day 15 No change	13 Participants	18 Participants
Number of Participants With Categorical KRT16 Expression at Day 15 Slight improvement	3 Participants	10 Participants
Number of Participants With Categorical KRT16 Expression at Day 15 Good improvement	8 Participants	5 Participants
Number of Participants With Categorical KRT16 Expression at Day 15 Excellent improvement	12 Participants	1 Participants
Number of Participants With Categorical KRT16 Expression at Day 15 Worsening	3 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 8

Population: All randomized participants who received at least 1 dose of investigational product.

The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Lesion Severity as Measured by TSS at Day 8	-3.3 units on a scale Standard Error 0.36	-1.2 units on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 8 and 15

Population: "Number of Participants Analyzed" signifies the number of participants who received at least 1 dose of investigational product. "Number Analyzed" refers to the number of evaluable participants for specified time points.

The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 Day 8	-1.3 units on a scale Standard Error 0.16	-0.4 units on a scale Standard Error 0.11
Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 Day 15	-1.9 units on a scale Standard Error 0.15	-0.8 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15

Population: "Number of Participants Analyzed" signifies the number of participants who received at least 1 dose of investigational product. "Number Analyzed" refers to the number of evaluable participants for specified time points.

The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 2	-1.9 units on a scale Standard Error 0.36	-1.0 units on a scale Standard Error 0.31
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 3	-2.2 units on a scale Standard Error 0.36	-0.9 units on a scale Standard Error 0.38
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 4	-2.4 units on a scale Standard Error 0.33	-1.1 units on a scale Standard Error 0.33
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 5	-2.7 units on a scale Standard Error 0.31	-1.1 units on a scale Standard Error 0.36
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 6	-2.6 units on a scale Standard Error 0.34	-1.3 units on a scale Standard Error 0.36
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 7	-3.1 units on a scale Standard Error 0.36	-1.5 units on a scale Standard Error 0.35
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 8	-3.4 units on a scale Standard Error 0.35	-1.5 units on a scale Standard Error 0.33
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 9	-3.4 units on a scale Standard Error 0.32	-1.5 units on a scale Standard Error 0.34
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 10	-3.5 units on a scale Standard Error 0.34	-1.6 units on a scale Standard Error 0.32
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 11	-3.5 units on a scale Standard Error 0.41	-2.0 units on a scale Standard Error 0.41
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 12	-3.7 units on a scale Standard Error 0.40	-1.5 units on a scale Standard Error 0.36
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 13	-4.0 units on a scale Standard Error 0.38	-2.2 units on a scale Standard Error 0.39
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 14	-3.9 units on a scale Standard Error 0.36	-2.2 units on a scale Standard Error 0.37
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 Day 15	-3.9 units on a scale Standard Error 0.38	-2.0 units on a scale Standard Error 0.41

SECONDARY outcome

Timeframe: From first dose of study treatment up to Day 71

Population: All participants in each treatment group who received at least 1 dose of investigational product.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=39 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups Treatment-emergent AEs	27 Participants	16 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups Treatment-emergent SAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection

Population: This outcome measure was summarized by the treatment areas during the double-blind period; therefore, the analysis population here represents the participants who received at least 1 dose of investigational product for each treatment area in double-blind period.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.

Outcome measures

Measure	Crisaborole Ointment 2% Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the target lesions that were treated with crisaborole ointment 2% during Days 1 to 14.	Vehicle Treated Lesion n=40 Participants On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14.
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Application site dermatitis	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Application site erythema	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Application site pain	2 Participants	4 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Application site pruritus	1 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Application site folliculitis	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Post procedural haemorrhage	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Procedural pain	2 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period Suture related complication	1 Participants	2 Participants

Adverse Events

Crisaborole Ointment 2% + Vehicle in Double-Blind Period

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Crisaborole Ointment 2% in Open-Label Period

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Crisaborole Ointment 2% + Vehicle in Double-Blind Period n=40 participants at risk On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the participants who were treated with both crisaborole ointment 2% and vehicle during Days 1 to 14.	Crisaborole Ointment 2% in Open-Label Period n=39 participants at risk On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp).
General disorders Application site pain	10.0% 4/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	10.3% 4/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Gastroenteritis	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	5.1% 2/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Nasopharyngitis	17.5% 7/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	12.8% 5/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Injury, poisoning and procedural complications Procedural pain	15.0% 6/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Injury, poisoning and procedural complications Suture related complication	10.0% 4/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Musculoskeletal and connective tissue disorders Back pain	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	5.1% 2/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Nervous system disorders Headache	20.0% 8/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Skin and subcutaneous tissue disorders Dermatitis atopic	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	12.8% 5/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Eye disorders Noninfective conjunctivitis	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Gastrointestinal disorders Constipation	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Gastrointestinal disorders Diarrhoea	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Gastrointestinal disorders Gastrooesophageal reflux disease	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Gastrointestinal disorders Nausea	5.0% 2/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Application site dermatitis	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Application site erythema	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Application site paraesthesia	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Application site pruritus	5.0% 2/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Fatigue	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
General disorders Injection site pain	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Application site folliculitis	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Cystitis	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Paronychia	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Infections and infestations Vulvovaginal candidiasis	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Injury, poisoning and procedural complications Graft complication	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Injury, poisoning and procedural complications Post procedural haemorrhage	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Musculoskeletal and connective tissue disorders Arthralgia	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Musculoskeletal and connective tissue disorders Myalgia	5.0% 2/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	2.6% 1/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Nervous system disorders Burning sensation	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Nervous system disorders Dizziness	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Nervous system disorders Paraesthesia	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Nervous system disorders Presyncope	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 2/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Skin and subcutaneous tissue disorders Night sweats	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).
Skin and subcutaneous tissue disorders Skin plaque	2.5% 1/40 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).	0.00% 0/39 • From first dose of study treatment up to Day 71 Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see Outcome Measure 19 for the treated area AEs).

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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