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Trial record 78 of 154 for:    Dermatitis, Atopic, 8

Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis

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ClinicalTrials.gov Identifier: NCT03233529
Recruitment Status : Completed
First Posted : July 28, 2017
Results First Posted : August 13, 2019
Last Update Posted : August 13, 2019
Sponsor:
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: Basic Science
Condition Dermatitis, Atopic
Interventions Drug: Crisaborole ointment 2% BID
Drug: Placebo ointment (vehicle)
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2%
Hide Arm/Group Description 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.
Period Title: Double-Blind Period (Day 1 to Day 15)
Started 40
Completed 39
Not Completed 1
Reason Not Completed
Adverse Event             1
Period Title: Open-Label Period (Day 15 to Day 71)
Started 39
Completed 38
Not Completed 1
Reason Not Completed
Adverse Event             1
Arm/Group Title Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2%
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
32.2  (11.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
27
  67.5%
Male
13
  32.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Hispanic or Latino
3
   7.5%
Not Hispanic or Latino
37
  92.5%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   7.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
   7.5%
White
34
  85.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: units on a scale
-4.5  (0.31) -2.1  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-3.1 to -1.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.35
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-1.2787  (0.36339) -0.2881  (0.34055)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0420
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.9906
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48404
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-0.7295  (0.25784) -0.1849  (0.25272)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1519
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.5446
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37855
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-1.3267  (0.24359) -0.1994  (0.22335)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.1273
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.32552
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-0.5484  (0.25767) 0.2128  (0.27893)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0871
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.7612
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44266
Estimation Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-2.4495  (0.30229) -1.0854  (0.33131)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.3641
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48603
Estimation Comments [Not Specified]
7.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-2.4235  (0.33463) -1.2989  (0.35218)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0238
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.1246
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.49359
Estimation Comments [Not Specified]
8.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
-3.2762  (0.39686) -1.2849  (0.40613)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0042
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.9913
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.68659
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2-scale micrometers
-0.2737  (0.10653) -0.1779  (0.08229)
10.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2-scale cells per square millimeter
CD11c -0.4736  (0.18946) -0.1694  (0.11081)
CD3 -0.6219  (0.15152) -0.2642  (0.13959)
FceR1 -0.4226  (0.16068) -0.1314  (0.16513)
Ki67 -1.0983  (0.21512) -0.8971  (0.19918)
Langerin 0.3694  (0.27896) 0.2779  (0.19645)
11.Secondary Outcome
Title Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Mean (Standard Error)
Unit of Measure: log2(normalized expression)
CCL13 -0.3095  (0.21520) 0.0604  (0.20967)
CCL20 -0.2016  (0.23629) 0.1088  (0.23212)
CCL26 0.0231  (0.18602) 0.1195  (0.22820)
CRLF2 -0.8058  (0.13728) -0.2023  (0.14431)
CXCL1 -1.4174  (0.23956) 0.1924  (0.32423)
CXCL10 -1.0779  (0.36531) 0.6697  (0.37822)
CXCL2 -0.5462  (0.21129) 0.1945  (0.20700)
CXCL9 -0.9941  (0.33692) 0.7562  (0.39811)
DEFB4A -3.5331  (0.42635) -1.3456  (0.46988)
FLG -0.2155  (0.18503) -0.3670  (0.22285)
FOXP3 -0.5115  (0.12709) -0.0273  (0.16057)
IFNG -0.5588  (0.34472) 0.5737  (0.31138)
IL-10 -0.3773  (0.19458) 0.2950  (0.17314)
IL-15 -0.2307  (0.12331) 0.2193  (0.11761)
IL-15RA -0.0780  (0.10814) 0.2110  (0.10624)
IL-17A -1.1577  (0.57223) 0.7516  (0.59970)
IL-17F -1.9482  (0.79294) 0.5309  (0.88038)
IL-19 -3.1946  (0.78012) -0.8108  (0.75460)
IL-1B -0.5792  (0.21864) 0.2808  (0.29124)
IL-2 -0.5352  (0.26229) 0.2769  (0.16896)
IL-22 -1.4970  (0.39951) -0.0170  (0.35503)
IL-2RA -0.8836  (0.19462) -0.0824  (0.22176)
IL-31 -1.5885  (0.60512) -0.3997  (0.65363)
IL-32 -0.2992  (0.16762) 0.1878  (0.15632)
IL-5 -0.3487  (0.51329) -0.4148  (0.42311)
IL-6 -0.8814  (0.32670) 0.1724  (0.36369)
IL-8 -1.9805  (0.37922) -0.1698  (0.42603)
IL-9 -2.2803  (0.71683) -1.0530  (0.68305)
IL-12A 0.2787  (0.20557) 0.5251  (0.16751)
IL-23A -1.2754  (0.26058) -0.1173  (0.28133)
LOR 0.3759  (0.19707) -0.1041  (0.21965)
MMP-12 -1.9588  (0.39817) -0.4205  (0.34033)
PDE4A 0.0105  (0.12015) 0.1359  (0.11153)
PDE4B -0.1900  (0.12061) 0.1923  (0.10897)
PDE4D -0.3865  (0.12920) 0.0736  (0.12231)
PPL -0.3000  (0.09781) -0.1933  (0.12180)
RNA18SP5 0.1121  (0.08576) -0.0221  (0.06550)
S100A7 -2.1764  (0.30729) -0.8782  (0.26498)
S100A8 -2.4454  (0.36057) -1.0669  (0.33255)
S100A9 -2.6155  (0.35209) -1.2976  (0.33324)
12.Secondary Outcome
Title Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15
Hide Description 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.
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Measure Type: Count of Participants
Unit of Measure: Participants
No change
10
  25.6%
19
  48.7%
Partial normalization
10
  25.6%
5
  12.8%
Full normalization
12
  30.8%
4
  10.3%
Worsening
7
  17.9%
11
  28.2%
13.Secondary Outcome
Title Number of Participants With Categorical Histological Response at Day 15
Hide Description 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.
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Measure Type: Count of Participants
Unit of Measure: Participants
Non-responder
18
  46.2%
30
  76.9%
Responder
21
  53.8%
9
  23.1%
14.Secondary Outcome
Title Number of Participants With Categorical KRT16 Expression at Day 15
Hide Description 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.
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 39
Measure Type: Count of Participants
Unit of Measure: Participants
No change
13
  33.3%
18
  46.2%
Slight improvement
3
   7.7%
10
  25.6%
Good improvement
8
  20.5%
5
  12.8%
Excellent improvement
12
  30.8%
1
   2.6%
Worsening
3
   7.7%
5
  12.8%
15.Secondary Outcome
Title Change From Baseline in Lesion Severity as Measured by TSS at Day 8
Hide Description 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.
Time Frame Baseline (Day 1), Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of investigational product.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 40
Mean (Standard Error)
Unit of Measure: units on a scale
-3.3  (0.36) -1.2  (0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-2.7 to -1.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Days 8 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
"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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 40
Mean (Standard Error)
Unit of Measure: units on a scale
Day 8 Number Analyzed 40 participants 40 participants
-1.3  (0.16) -0.4  (0.11)
Day 15 Number Analyzed 39 participants 39 participants
-1.9  (0.15) -0.8  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.3 to -0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments Comparison at Day 8
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-1.4 to -0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments Comparison at Day 15
17.Secondary Outcome
Title Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15
Hide Description 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.
Time Frame Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
Hide Outcome Measure Data
Hide Analysis Population Description
"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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 40
Mean (Standard Error)
Unit of Measure: units on a scale
Day 2 Number Analyzed 39 participants 39 participants
-1.9  (0.36) -1.0  (0.31)
Day 3 Number Analyzed 39 participants 39 participants
-2.2  (0.36) -0.9  (0.38)
Day 4 Number Analyzed 40 participants 40 participants
-2.4  (0.33) -1.1  (0.33)
Day 5 Number Analyzed 38 participants 38 participants
-2.7  (0.31) -1.1  (0.36)
Day 6 Number Analyzed 39 participants 39 participants
-2.6  (0.34) -1.3  (0.36)
Day 7 Number Analyzed 39 participants 39 participants
-3.1  (0.36) -1.5  (0.35)
Day 8 Number Analyzed 39 participants 39 participants
-3.4  (0.35) -1.5  (0.33)
Day 9 Number Analyzed 39 participants 39 participants
-3.4  (0.32) -1.5  (0.34)
Day 10 Number Analyzed 39 participants 39 participants
-3.5  (0.34) -1.6  (0.32)
Day 11 Number Analyzed 37 participants 37 participants
-3.5  (0.41) -2.0  (0.41)
Day 12 Number Analyzed 39 participants 39 participants
-3.7  (0.40) -1.5  (0.36)
Day 13 Number Analyzed 39 participants 39 participants
-4.0  (0.38) -2.2  (0.39)
Day 14 Number Analyzed 39 participants 39 participants
-3.9  (0.36) -2.2  (0.37)
Day 15 Number Analyzed 39 participants 39 participants
-3.9  (0.38) -2.0  (0.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0188
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-1.6 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 2
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-1.9 to -0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 3
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.0 to -0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 4
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.2 to -0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 5
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.0 to -0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 6
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.3 to -0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 7
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-2.5 to -1.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 8
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-2.6 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 9
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-2.7 to -1.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 10
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.3 to -0.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments Comparison at Day 11
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-2.9 to -1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 12
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-2.6 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 13
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-2.4 to -1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 14
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Crisaborole Ointment 2% Treated Lesion, Vehicle Treated Lesion
Comments Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Square Mean of Difference
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-2.7 to -1.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments Comparison at Day 15
18.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups
Hide Description 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).
Time Frame From first dose of study treatment up to Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in each treatment group who received at least 1 dose of investigational product.
Arm/Group Title Crisaborole Ointment 2% + Vehicle in Double-Blind Period Crisaborole Ointment 2% in Open-Label Period
Hide Arm/Group Description:
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.
On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp).
Overall Number of Participants Analyzed 40 39
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment-emergent AEs
27
  67.5%
16
  41.0%
Treatment-emergent SAEs
0
   0.0%
0
   0.0%
19.Secondary Outcome
Title 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
Hide Description 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.
Time Frame From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crisaborole Ointment 2% Treated Lesion Vehicle Treated Lesion
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 40 40
Measure Type: Count of Participants
Unit of Measure: Participants
Application site dermatitis
0
   0.0%
1
   2.5%
Application site erythema
1
   2.5%
0
   0.0%
Application site pain
2
   5.0%
4
  10.0%
Application site pruritus
1
   2.5%
2
   5.0%
Application site folliculitis
1
   2.5%
0
   0.0%
Post procedural haemorrhage
0
   0.0%
1
   2.5%
Procedural pain
2
   5.0%
2
   5.0%
Suture related complication
1
   2.5%
2
   5.0%
Time Frame From first dose of study treatment up to Day 71
Adverse Event Reporting Description 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).
 
Arm/Group Title Crisaborole Ointment 2% + Vehicle in Double-Blind Period Crisaborole Ointment 2% in Open-Label Period
Hide Arm/Group Description 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. On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp).
All-Cause Mortality
Crisaborole Ointment 2% + Vehicle in Double-Blind Period Crisaborole Ointment 2% in Open-Label Period
Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)   0/39 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Crisaborole Ointment 2% + Vehicle in Double-Blind Period Crisaborole Ointment 2% in Open-Label Period
Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)   0/39 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Crisaborole Ointment 2% + Vehicle in Double-Blind Period Crisaborole Ointment 2% in Open-Label Period
Affected / at Risk (%) Affected / at Risk (%)
Total   27/40 (67.50%)   16/39 (41.03%) 
Eye disorders     
Noninfective conjunctivitis * 1  0/40 (0.00%)  1/39 (2.56%) 
Gastrointestinal disorders     
Constipation * 1  1/40 (2.50%)  0/39 (0.00%) 
Diarrhoea * 1  1/40 (2.50%)  0/39 (0.00%) 
Gastrooesophageal reflux disease * 1  1/40 (2.50%)  0/39 (0.00%) 
Nausea * 1  2/40 (5.00%)  0/39 (0.00%) 
General disorders     
Application site pain * 1  4/40 (10.00%)  4/39 (10.26%) 
Application site dermatitis * 1  1/40 (2.50%)  0/39 (0.00%) 
Application site erythema * 1  1/40 (2.50%)  0/39 (0.00%) 
Application site paraesthesia * 1  0/40 (0.00%)  1/39 (2.56%) 
Application site pruritus * 1  2/40 (5.00%)  0/39 (0.00%) 
Fatigue * 1  1/40 (2.50%)  0/39 (0.00%) 
Injection site pain * 1  0/40 (0.00%)  1/39 (2.56%) 
Infections and infestations     
Gastroenteritis * 1  0/40 (0.00%)  2/39 (5.13%) 
Nasopharyngitis * 1  7/40 (17.50%)  5/39 (12.82%) 
Application site folliculitis * 1  1/40 (2.50%)  0/39 (0.00%) 
Cystitis * 1  0/40 (0.00%)  1/39 (2.56%) 
Paronychia * 1  1/40 (2.50%)  0/39 (0.00%) 
Vulvovaginal candidiasis * 1  0/40 (0.00%)  1/39 (2.56%) 
Injury, poisoning and procedural complications     
Procedural pain * 1  6/40 (15.00%)  1/39 (2.56%) 
Suture related complication * 1  4/40 (10.00%)  1/39 (2.56%) 
Graft complication * 1  0/40 (0.00%)  1/39 (2.56%) 
Post procedural haemorrhage * 1  1/40 (2.50%)  0/39 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/40 (2.50%)  2/39 (5.13%) 
Arthralgia * 1  1/40 (2.50%)  0/39 (0.00%) 
Myalgia * 1  2/40 (5.00%)  0/39 (0.00%) 
Pain in extremity * 1  0/40 (0.00%)  1/39 (2.56%) 
Nervous system disorders     
Headache * 1  8/40 (20.00%)  1/39 (2.56%) 
Burning sensation * 1  1/40 (2.50%)  0/39 (0.00%) 
Dizziness * 1  1/40 (2.50%)  0/39 (0.00%) 
Paraesthesia * 1  1/40 (2.50%)  0/39 (0.00%) 
Presyncope * 1  1/40 (2.50%)  0/39 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain * 1  2/40 (5.00%)  0/39 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis atopic * 1  1/40 (2.50%)  5/39 (12.82%) 
Night sweats * 1  1/40 (2.50%)  0/39 (0.00%) 
Skin plaque * 1  1/40 (2.50%)  0/39 (0.00%) 
1
Term from vocabulary, MedDRA v21.0
*
Indicates events were collected by non-systematic assessment
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
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03233529     History of Changes
Other Study ID Numbers: C3291001
First Submitted: July 12, 2017
First Posted: July 28, 2017
Results First Submitted: April 26, 2019
Results First Posted: August 13, 2019
Last Update Posted: August 13, 2019