Safety and Efficacy of Doses of LEO 43204 Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis

Study Overview
=================
Brief Summary
-----------------
To identify the Maximum Tolerated Dose levels of LEO 43204 after once daily treatment for two consecutive days and to evaluate efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle

Official Title
-----------------
Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Full Balding Scalp in Subjects With Actinic Keratosis

Conditions
-----------------
Actinic Keratosis

Intervention / Treatment
-----------------
* Drug: LEO 43204
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the full balding scalp. Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the full balding scalp Exclusion Criteria: Location of the treatment area within 5 cm of an incompletely healed wound within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) Prior treatment with ingenol mebutate gel on the treatment area Lesions in the treatment areas that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions)

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Part 1: LEO 43204<br>Open-label, dose escalation, 2 days treatment | Drug: LEO 43204<br> <br> |
| Active Comparator: Part 2: LEO 43204 x dose<br>X dose for 2 days treatment | Drug: LEO 43204<br> <br> |
| Active Comparator: Part 2: LEO 43204 Y dose<br>Y dose for 2 days treatment | Drug: LEO 43204<br> <br> |
| Placebo Comparator: Part 2: Placebo<br>Placebo for 2 days treatment | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | The number participants experiencing a DLT was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants experiencing a DLT. A DLT was defined as: Erosion/ulceration Grade 4 on the Local Skin Response (LSR) scale Other clinically relevant signs or symptoms observed, which the International Co-ordinating Investigator judges to be counted as a DLT. The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. | From Day 1 up to and including Day 8 | 
| Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count | Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) in the selected treatment area. | From baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Participants With Complete Clearance of AKs | Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in AK count. | From baseline to Week 8 | 
| Part 2: Participants With Partial Clearance of AKs | Partial clearance of AKs at Week 8 was defined as at least 75% reduction from baseline in AK count. | From baseline to Week 8 |