Safety and Dose Finding Study of New Vehicle Formulations Containing Ingenol Mebutate to Treat Actinic Keratosis on the Forearm

Study Overview
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Brief Summary
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The purpose of this study is to determine if the new vehicle formulations containing ingenol mebutate are as safe and effective as Picato® gel 0.05% (it's current vehicle formulation) when applied to AK lesions on the forearm for two consecutive days.

Detailed Description
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This study will be run in 2 parts. The first part involves applying escalating concentrations of the new vehicle formulations containing ingenol mebutate to AKs on the forearms. Reactions and safety will be compared to Picato® (a registered and marketed ingenol mebutate gel) to ascertain if the new vehicle formulations are at least as safe and effective as Picato® . The purpose of part 2 is to select the concentration in the new formulation that produces this same, if not better response, as Picato® and with a similar or better safety profile.

Official Title
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A Seamless Phase 1/2 Exploratory Multi-centre, Investigator-blind, Dose Escalation Study (Study Part 1), Followed by a Randomised, Intra-subject, Active Controlled Efficacy Study of Different Ingenol Mebutate Formulations Applied to the Forearm for 2 Consecutive Days (Study Part 2)

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: once daily for two consecutive days (Picato)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be male or female and at least 18 years of age. Female patients must be of non-childbearing potential or if of childbearing potential then negative serum and urine pregnancy test and using effective contraception. Ability to provide informed consent. Exclusion Criteria: location of the selected treatment area within 5cm of an incompletely healed wound or within 5cm of a suspected basal cell carcinoma or squamous cell carcinoma undergone Cosmetic or therapeutic procedures within 2cm of the selected treatment area in the 2 weeks prior to the treatment visit presence of sunburn within the selected treatment areas use of acid-containing therapeutic products within 2cm of the selected treatment area in the 2 weeks prior to the treatment visit previous enrolment in this clinical trial prior treatment with ingenol mebutate on the forearms use of topical moisturisers/creams/lotions, artificial tanners or topical steroids within 2cm of the selected treatment areas in the 2 weeks prior to the treatment visit treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system within 4 weeks of the treatment visit treatment with 5-FU, imiquimod, diclofenac,or photodynamic therapy within 2 cm of the treatment area in the 8 weeks prior to the treatment visit use of systemic retinoids those who are currently participating in any other clinical trial females who are pregnant or are breastfeeding those known or suspected or not being able to comply with the requirements of the protocol or provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Picato® 0.05% gel<br>once daily for two consecutive days | Drug: once daily for two consecutive days (Picato)<br> <br> * Other names: escalating doses of ingenol mebutate vehicle formulation 3;|
| Experimental: ingenol mebutate vehicle formulation 1<br>once daily for two consecutive days | Drug: once daily for two consecutive days (Picato)<br> <br> * Other names: escalating doses of ingenol mebutate vehicle formulation 3;|
| Experimental: ingenol mebutate vehicle formulation 2<br>once daily for two consecutive days | Drug: once daily for two consecutive days (Picato)<br> <br> * Other names: escalating doses of ingenol mebutate vehicle formulation 3;|
| Experimental: ingenol mebutate vehicle formulation 3<br>once daily for two consecutive days | Drug: once daily for two consecutive days (Picato)<br> <br> * Other names: escalating doses of ingenol mebutate vehicle formulation 3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of 3 new vehicle formulations containing ingenol mebutate compared to Picato® gel applied topically once daily for two consecutive days to four separate treatment areas containing actinic keratosis on the forearm | Safety data to be collected via CRF entries of AEs/SAEs and photographs. Relative skin reactions for comparison to Picato®. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate treatment responses on AK of selected concentration of ingenol mebutate containing vehicle formulation from Part 1 compared to Picato® gel as assessed by reduction in the number of selected AK lesions 2 months after treatment | Assessed by visible and imaged lesion count | 2 months |