Percentage of Participants Achieving Investigator's Global Assessment (IGA) Score Clear (0) or Almost Clear (1) and a Reduction From Baseline of Greater Than or Equal to ( >=2) Points at Week 6: Non-responder Imputation
IGA assesses severity of participant's AD on a 5 point scale. 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting and 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Higher scores indicating more severity of AD. Assessment excluded soles, palms and scalp.
Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6: Multiple Imputation
EASI evaluates severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions(head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Percentage of Participants Achieving >=2 Points Reduction in Peak Pruritus Numerical Rating Scale (PP-NRS) From Baseline at Weeks 1, 2, 3, 4 and 6: Non-responder Imputation
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants at specified time points were asked the following question: "How would you rate your itch due to AD at the worst moment during the previous 24 hours?" The scale ranged from 0-10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Percentage of Participants Achieving >=4 Points Reduction in Peak Pruritus Numerical Rating Scale (PP-NRS) From Baseline at Weeks 1, 2, 3, 4, 6 and Follow-up Visit: Non-responder Imputation
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants at specified time points were asked the following question: "How would you rate your itch due to AD at the worst moment during the previous 24 hours?" The scale ranged from 0-10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Percent Change From Baseline in Affected Body Surface Area (BSA) at Weeks 1, 2, 3, 4, 6 and Follow-up Visit
4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranged from 0 to 100%, with higher values representing greater severity of AD.
Percentage of Participants Achieving >=75% Improvement in Eczema Area and Severity Index Total Score (EASI-75) From Baseline at Weeks 1, 2, 3, 4 and 6: Non-responder Imputation
EASI evaluates severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions(head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product 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; medically important events. Treatment-emergent were events between first dose of investigational product and up to 28 days after the last dose of investigational product that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Number of Participants With Pre-defined Criteria For Vital Signs
Pre-defined criteria included: 1) Diastolic blood pressure (DBP), a) sitting DBP: change of >= 20 millimeter of mercury (mmHg) increase, b) sitting DBP: change of >=20mmHg decrease, c) supine DBP: less than (<) 50 mmHg, d) supine DBP: change of >= 20mmHg increase, e) supine DBP: change of >= 20mmHg decrease; 2) Systolic blood pressure (SBP), a) sitting SBP: <90 mmHg, b) sitting SBP: change of >=30mmHg increase, c) sitting SBP: change of >=30mmHg decrease, d) supine SBP: change of >=30mmHg increase, e) supine SBP: change of >=30mmHg decrease and f) Supine SBP: value <90mmHg.
Number of Participants With Laboratory Abnormalities
Hemoglobin (HGB),hematocrit,erythrocytes (ery.),HDL cholesterol (chl.)<0.8*lower limit of normal(LLN);reticulocytes (ret.), ret./ery. (%)<0.5*LLN,>1.5*upper limit of normal (ULN);ery. mean corpuscular (EMC) volume,EMC HGB,EMC HGB concentration,potassium,chloride,calcium,bicarbonate<0.9*LLN,>1.1*ULN;platelets<0.5*LLN,>1.75*ULN;leukocytes (leu.),glucose<0.6*LLN,>1.5*ULN;lymphocytes (lym.), lym./leu.(%), neutrophils (neu.), neu./leu. (%), protein,albumin <0.8*LLN,>1.2*ULN;basophils (bas.), bas./leu.(%), eosinophils (eos.), eos./leu., monocytes (mon.), mon./leu.(%), urate >1.2*ULN;bilirubin (total, direct, indirect)>1.5*ULN;aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase>3.0*ULN;urea nitrogen, creatinine, triglycerides, chl.>1.3*ULN; sodium <0.95*LLN,>1.05*ULN; creatine kinase >2.0*ULN;Urine: pH<4.5,>8;glucose, ketones, protein, HGB, urobilinogen,bilirubin,nitrite,leukocyte esterase>=1;ery., leu.>= 20;hyaline casts>1;bacteria>20.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
Clinically significant ECG criteria included PR interval: value greater than (>) 280 millisecond (msec), percentage change greater than equal to (>=) 25/50 percentage, QRS interval: value >120 msec, percentage change >= 50% and QT interval corrected using the Fridericia's formula (QTCF) value 450 msec and 30<=change<60.
Change From Baseline in Clinical Chemistry-Lactate Dehydrogenase Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Clinical Chemistry- Protein and Albumin Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Clinical Chemistry- Urea Nitrogen, Urate, Calcium and Glucose Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Clinical Chemistry- Sodium, Potassium, Chloride and Bicarbonate Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Hematology- Hemoglobin Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Hematology - Hematocrit, Reticulocytes/Erythrocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes, Basophils/Leukocytes, Eosinophils/Leukocytes and Monocytes/Leukocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Hematology- Erythrocytes and Reticulocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Hematology- Platelets, Leukocytes, Lymphocytes, Neutrophils, Basophils, Eosinophils and Monocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit
Change From Baseline in Lipids Profile Values at Week 6
Lipid parameters that were assessed: high density lipoprotein (HDL) cholesterol, triglycerides, cholesterol, low density lipoprotein (LDL) cholesterol.
Change From Baseline in Ratio of LDL Cholesterol to HDL Cholesterol Lipids Profile at Week 6
Mean change in total cholesterol/HDL cholesterol ratio was assessed and reported.
Change From Baseline in Electrocardiogram (ECG) Parameter- Heart Rate at Weeks 2 and 6
Change From Baseline in PR, QRS, QTCF and QT Interval at Weeks 2 and 6
Change From Baseline in Vital Signs- Blood Pressure (BP) at Weeks 2 and 6
Blood pressure included supine and sitting systolic and diastolic BP.
Change From Baseline in Vital Signs- Pulse Rate at Weeks 2 and 6
Change From Baseline in Vital Signs- Temperature at Weeks 2 and 6
Number of Participants With Each Severity Grade in Local Tolerability Assessments
Local tolerability skin assessments were performed by the investigator and graded based on severity from grade 0 to 4 as: grade 0=none (no evidence of local intolerance); grade 1=mild (minimal erythema and/or oedema, slight glazed appearance); grade 2= moderate (definite erythema and/or oedema with peeling and/or cracking but needs no adaptation of posology) grade 3=severe (erythema, oedema glazing with fissures, few vesicles or papules consider removing topical agent [if still in place]) and grade 4= very severe (strong reaction spreading beyond the treated area, bullous reaction, erosions: removal of topical agent [if still in place]). Higher grades indicated worsening of condition. Only those categories in which at least 1 participant had data were reported.