Safety, Tolerability and Pharmacokinetics of LEO 29102 Cream in Atopic Dermatitis.

Study Overview
=================
Brief Summary
-----------------
The purpose of this Phase Ib study is to investigate the safety, tolerability and pharmacokinetics of LEO 29102 2,5 mg/g cream when treating atopic dermatitis (AD) lesions from 10 up to 100% of the body surface area (BSA) twice daily (BID) for 7 days (Cohorts I, II, III) and from 10% up to 50% of BSA (bid) for 6 weeks (Cohort IV). This trial will be performed in four cohorts. Cohort I, II and III includes patients with a larger BSA that increases from one cohort to the next. After each cohort (Cohort I, II)a blinded evaluation of the safety and tolerability data will assess whether a stepwise increase in the percentage of to be treated BSA is justified. Cohort IV will start dosing after finalisation of Cohort II and after submission of data from Cohort I and II to the national authority and IEC for review.

Official Title
-----------------
Safety, Tolerability and Pharmacokinetics of LEO 29102 Cream in Atopic Dermatitis. A Multicentre, Prospective, Randomised Phase Ib Study in Subjects Investigating Safety,Tolerability and Pharmacokinetics of LEO 29102 Cream (2.5 mg/g) When Treating Atopic Dermatitis Lesions Twice Daily for 7 Days (Cohorts I, II and III) and 6 Weeks (Cohort IV)

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: LEO 29102
* Drug: LEO 29102 Cream Vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of AD defined according to Hanifin and Rajka. Investigator Global Assessment scored as mild (2) to severe (4) AD. At screening, AD lesions amenable for treatment involving 10% to < 25% (Cohort I), 25% to < 50% (Cohort II), 50% to 100% (Cohort III) and 10% to < 50% (Cohort IV) of the total BSA. On Day -1, AD lesions amenable for treatment involving 10% to < 28% (Cohort I), 25% to < 55% (Cohort II), 50% to 100% (Cohort III) and 10% to < 55% (Cohort IV) of the total BSA. Adult male or female subjects, aged 18 to 65 years, inclusive.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 29102 2,5 mg/g cream<br> | Drug: LEO 29102<br>* Cream, 1,7mg/cm2 BSA, BID, 7 days In Cohort I, II and III, 6 weeks in Cohort IV<br>|
| Placebo Comparator: LEO 29102 Cream Vehicle<br> | Drug: LEO 29102 Cream Vehicle<br>* Cream, 1,7mg/cm2 BSA, BID, 7 days in Cohort I and II, 6 weeks in Cohort IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile - Cohort I, II, III | Cmax, AUC, Tmax | Predose, 1h, 2h, 4h, 6h, 12h, 13h, 14h, 16h, 18h, 24h (on day 1 and 7) and 36h, 48h, 72h (on day 7 only) | 
| Tolerability and safety of LEO 29102 cream - Cohort I, II, III | Number of subjects with AEs and change from baseline in vital signs (blood pressure, pulse rate, respiratory rate body temperature), ECG parameters, clinical laboratory, physical examination | 14 Days | 
| PK profile - Cohort IV | Cmax, AUC, Tmax | Day 1, 14, 28, 42: Pre AM dose and 1h, 2h, 4h, 6h, 12h. Post AM dose, but prior to PM dose and 24 h, 36h, 48h, 72h after AM dose Day 42 | 
| Tolerability and safety of LEO 29102 cream - Cohort IV | Number of subjects with AEs and change from baseline in vital signs (blood pressure, pulse rate, respiratory rate body temperature), ECG parameters, clinical laboratory, physical examination, SCORAD, EASI and IGA by stratum, treatment and visit. | 49 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermis concentration of LEO 29102 and its metabolites LEO 28386 and LEO 26989 after multiple topical applications in subjects with AD (Cohorts II and IV, Subgroup 1) |  | 10 Days for cohort II; 42 days for cohort IV, subgroup 1 | 
| Biomarkers in AD lesions before and after multiple topical applications in subjects with AD (Cohorts I and IV, Subgroup 2) |  | 10 Days for cohort I, 42 days for cohort IV, subgroup 2 |