Crisaborole for Chinese and Japanese Subjects (≥2 Years of Age) With Mild to Moderate Atopic Dermatitis

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

ISGA assessed the severity of atopic dermatitis (AD) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Improvement in ISGA is defined as ISGA score of 0 or 1.

ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Success in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline.

Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point NRS where 0 is no pruritus and 10 is worst itch imaginable. Change: score at Week 4 minus score at baseline.

ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Success in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline.

ISGA (Investigator's Static Global Assessment) assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD.

Improvement in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) .

The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of 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.

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp was excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated.

The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis.

EASI-50 is defined as EASI score has ≥50% improvement from baseline.

The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis.

EASI-75 is defined as EASI score has ≥75% improvement from baseline.

Peak Pruritus NRS is participants-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point NRS where 0 is no pruritus and 10 is worst itch imaginable.

Change: score at observation minus score at baseline.

Patient Reported Itch Severity Scale is a 5-point scale indicating no itchy to very itchy (ranged from 0 to 4, where 0=no itch to 4=worst itch imaginable) for participants ≥6 and <12 years of age.

Observer Reported Itch Severity Scale is an 11-point (ranged from 0 to 10, where 0=no itch to 10=worst itch imaginable) scale and must be completed by the observer (caregivers of participants) for participants <6 years of age.

The DLQI was a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. The questionnaire will be completed by all participants aged 16 years and older, based on the age at Screening Visit/time of informed consent/assent. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4-15 years) quality of life. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

The IDQOL was completed by observer for participants aged 2-3 years, based on the age at the Screening Visit/time of informed consent/assent. The IDQOL is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score the more quality of life is impaired.

The DFI was completed by all observer for participants aged 2-17 years, based on the age at Screening Visit/time of informed consent/assent. The minimum DFI score is 0; the maximum DFI score is 30. The higher score means worse outcome.

The POEM is a validated 7-item measure used to assess the impact of AD over the past week. The POEM contains 7 symptom based questions with responses rating number of days each symptom is experienced over the past week, from 0 (no days) to 4 (every day), with a maximum score of 28. Higher score means worse outcome.

The POEM is a validated 7-item measure used to assess the impact of AD over the past week. The POEM contains 7 symptom based questions with responses rating number of days each symptom is experienced over the past week, from 0 (no days) to 4 (every day), with a maximum score of 28. Higher score means worse outcome.

The PGIS (for participants 12 years and older) is a single item patient-rated measure of the participant's AD condition severity at a given point in time.

This single item instrument uses a 7-point rating scale, which range from 1 to 7, where 1=Not present to 7=Extremely severe.

The PGIC (for participants 12 years and older) was used to determine global improvement as assessed by the participant or caregiver. It was used as an anchor to define a responder definition for the peak pruritus scales for 'clinically important responder' and as a sensitivity analysis for defining a 'clinical important difference' on the peak pruritus scales.

This single item instrument is a 7-point rating scale, anchored by (1) 'very much improved' to (7) 'very much worse'.

The OGIS (for participants ≥2 and <12 years) is a single item observer-rated measure of the participant's AD condition severity at a given point in time.

This single item instrument uses a 7-point rating scale, which ranged from 1 to 7, where 1=Not present to 7=Extremely severe.

The OGIC (for participants ≥2 and <12 years ) was used to determine global improvement as assessed by the participant or caregiver. It was used as an anchor to define a responder definition for the peak pruritus scales for 'clinically important responder' and as a sensitivity analysis for defining a 'clinical important difference' on the peak pruritus scales.

This single item instrument is a 7-point rating scale, anchored by (1) 'very much improved' to (7) 'very much worse'.