A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY TO ASSESS THE ANTI-INFLAMMATORY PROPERTIES OF TOPICAL CRX-197 IN LESIONAL SKIN OF ADULT SUBJECTS WITH MILD TO MODERATE ATOPIC DERMATITIS

INTERVENTION: Product Name: CRx‐197 topical cream Pharmaceutical Form: Cream INN or Proposed INN: loratadine Concentration unit: % percent Concentration type: equal Concentration number: 0,3‐ INN or Proposed INN: nortriptyline Concentration unit: % percent Concentration type: equal Concentration number: 0,1‐ Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use Product Name: 0.1% nortriptyline Pharmaceutical Form: Cream INN or Proposed INN: nortriptyline Concentration unit: % percent Concentration type: equal Concentration number: 0,1‐ Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use CONDITION: mild to moderate atopic dermatitis PRIMARY OUTCOME: Main Objective: The primary objective of this study is to demonstrate the effectiveness, tolerability and safety of CRx‐197 in subjects with mild to moderate AD. Primary end point(s): Exploratory Efficacy Endpoints: ; • Differences in change from Baseline to Days 8, 15, 22 and 29, 36 and 43 in erythema measured by chromametry between the treatments within each cohort separately; • Difference in change from Baseline to Days 8, 15, 22, 29, 36 and 43 in ADSI between the treatments within each cohort separately; • Differences in change from Baseline to Days 8, 15, 22 and 29, 36 and 43 in TEWL between treatments within each cohort separately; ; Safety Endpoints:; • Safety and tolerability as assessed by treatment emergent adverse events (AEs), concomitant medications, change from baseline in physical exam, vital signs, laboratory values ; •Difference in change from Baseline to Days 8, 15, 22, 29, 36 and 43 in skin thickness measured by ultrasound at between the treatments within each cohort separately ; ; PK Exploratory Analysis:; • PK assessment of plasma levels at the Baseline Visit (prior to treatment), Day 22 and Day 43; Secondary Objective: INCLUSION CRITERIA: To be eligible to participate in this study, candidates must meet the following INCLUSION CRITERIA: ? I01 Subject must voluntarily give written informed consent ? I02 Subject must be 18 to 60 years of age ? I03 Subject must manifest mild to moderate AD diagnosed according to Hanifin and Rajka [Hanifin, 1980] • Two Lesional areas of 20‐50 cm2 ? ADSI lesional score =4 and <13 • Difference in ADSI lesional score between lesions treated in the same subject should not be greater than 1 ? I04 TEWL in the lesional areas at least 12 g/m2h ? I05 Subject must be free from a condition/disease that the investigator feels will interfere with the interpretation of the study results. ? I06 Females of childbearing potential should either be surgically sterile (hysterectomy or tubal ligation), or should use a highly effective medically accepted contraceptive regimen. A highly effective method of birth control is defined as those which result in a