Crisaborole 2%

The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.

An adverse event was considered as a treatment-emergent adverse event (TEAE) if the event started after the first dose of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.

Laboratory parameters included: hematology and chemistry. Clinically significant laboratory abnormalities are defined as abnormal values that have clinical manifestations or require medical intervention. Clinically significant laboratory criteria included Hemoglobin \<0.8 x lower limit of normal (LLN), Leukocytes \>1.5 x upper limit of normal (ULN), Lymphocytes \<0.8 x LLN, Lymphocytes/Leukocytes \>1.2 x ULN, Neutrophils \<0.8 x LLN, Neutrophils \>1.2x ULN, Neutrophils/Leukocytes \<0.8 x LLN, Basophils/Leukocytes \>1.2 x ULN, Eosinophils \>1.2 x ULN, Eosinophils/Leukocytes \>1.2 x ULN, Monocytes \>1.2 x ULN, Monocytes/Leukocytes (%) \>1.2 x ULN, Bicarbonate \<0.9 x LLN, and Glucose \>1.5x ULN.

Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participants in the seated position, after having sat/lied calmly for at least 5 minutes. Clinically significant vital signs criteria included Diastolic Blood Pressure (DBP) Value \<50 mmHg, DBP Change ≥20 mmHg increase, DBP Change ≥20 mmHg decrease, Pulse Rate Value \>120 beats per minute (bpm), Systolic Blood Pressure (SBP) Value \<90 mmHg, SBP Change ≥30 mmHg increase, SBP Change ≥30mmHg decrease

The duration of flare-free maintenance was the time from randomization to the last Investigator's Static Global Assessment (ISGA) and was right censored, if an intercurrent event (eg, death, dropout, loss to follow up, or end of study) occurred before the first flare. When a flare occurred first, the duration of flare free maintenance was the time from randomization to the first flare and was not censored. Duration of flare free maintenance was estimated using the Kaplan-Meier method.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started on or after the treatment period start date and before end of study (at least 28 days after last dose of study intervention).

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

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.

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.

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.

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.

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.

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.

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.

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.

The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.

An 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; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.

Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.

Laboratory tests abnormalities included: hematology (haemoglobin\[Hb\], haematocrit and erythrocytes\<0.8\*lower limit of normal\[LLN\]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration \<0.9\*LLN and \>1.1\*upper limit of normal\[ULN\]; platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes/leukocytes\[%\], neutrophils/leukocytes\[%\] \<0.8\*LLN and \>1.2\*ULN; basophils/leukocytes\[%\], eosinophils/leukocytes\[%\], monocytes/leukocytes\[% \]\>1.2\*ULN); clinical chemistry(bilirubin\>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase\>3.0\*ULN; protein and albumin\<0.8\*LLN and \>1.2\*ULN; urea nitrogen and creatinine \>1.3\*ULN; urate\>1.2\*ULN; sodium \<0.95\*LLN and \>1.05\*ULN; potassium, chloride and calcium \<0.9\*LLN and \>1.1\*ULN; fasting glucose \<0.6\*LLN and \>1.5\*ULN); and urinalysis (pH \<4.5 and \>8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase \>=1).

Criteria for clinically significant ECG abnormalities included: QT interval \>=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) \>=450 msec to \<480 msec, \>=480 msec and \>=500 msec; increase from baseline in QTcF interval \>=30 msec to \<60 msec and \>=60 msec.