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

• LEO 43204 (Drug)
• Placebo (Drug)

Primary outcomes

• Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) [From Day 1 up to and including Day 8]: 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.
• Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count [From baseline to Week 8]: Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) in the selected treatment area.

Secondary outcomes

• Part 2: Participants With Complete Clearance of AKs [From baseline to Week 8]: Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in AK count.
• Part 2: Participants With Partial Clearance of AKs [From baseline to Week 8]: Partial clearance of AKs at Week 8 was defined as at least 75% reduction from baseline in AK count.

Sex: All, ages: 18 Years to any

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)

Participant flow

Outcome results

• Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) (Primary), Count of participants, Participants: Part 1 - 0.018% Cohort 0; Part 1 - 0.025% Cohort 0; Part 1 - 0.037% Cohort 0; Part 1 - 0.05% Cohort 0; Part 1 - 0.075% Cohort 0
• Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count (Primary), Mean, percentage of reduction: Part 2 - Vehicle 12.6 (-9.5 to 30.3); Part 2 - 0.037% 72.7 (66.9 to 77.5); Part 2 - 0.05% 78.5 (73.7 to 82.5) (p <0.001)
• Part 2: Participants With Complete Clearance of AKs (Secondary), Number, percentage of participants: Part 2 - Vehicle 3.1 (0.1 to 16.2); Part 2 - 0.037% 21.9 (12.5 to 34); Part 2 - 0.05% 29.9 (19.3 to 42.3) (p =0.007)
• Part 2: Participants With Partial Clearance of AKs (Secondary), Number, percentage of participants: Part 2 - Vehicle 6.3 (0.8 to 20.8); Part 2 - 0.037% 54.7 (41.7 to 67.2); Part 2 - 0.05% 59.7 (47.0 to 71.5) (p <0.001)

Adverse events

Time frame: Part 1: From Day 1 to Week 2 Part 2: From Day 1 to Week 8

Serious adverse events by term

Other adverse events by term

13 more terms not shown.

• Jonathan Weiss, MD, Principal investigator, Gwinnett Clinical Research Center, Inc.

NIH grants: 2014