Safety and Tolerability of Different Concentrations of an Ingenol Derivative Field Therapy in the Treatment of Actinic Keratosis

Study Overview
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Brief Summary
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The purpose of this study is to determine if the new ingenol derivative gels are as safe as and as well tolerated as ingenol mebutate gel when applied to AK lesions on the forearm for two consecutive days.

Detailed Description
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Various concentrations of new ingenol derivatives will be applied to AKs on the forearms. Reactions and safety will be compared to a US registered and marketed ingenol gel to ascertain if the new ingenol is at least as safe and as well tolerated as the registered ingenol.

Official Title
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A Phase 1 Exploratory Trial Evaluating Safety and Tolerability of Topical Administration of Different Concentrations of an Ingenol Derivative Compared to Ingenol Mebutate Gel 0.05% Applied on Two Consecutive Days to Four Separate 25cm2 Treatment Areas on the Forearms of Subjects With Actinic Keratosis (Field Therapy)

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: Ingenol once daily for two consecutive days


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 Visit 2 use of acid-containing therapeutic products within 2cm of the selected treatment area in the 2 weeks prior to Visit 2 use of topical moisturisers/creams/lotions, artificial tanners or topical steroids within 2cm of the selected treatment areas in the 2 weeks prior to visit 2 Treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system within 4 weeks of Visit 2 Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy within 2 cm of the treatment area in the 8 weeks prior to visit 2 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 of 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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ingenol mebutate gel 0.05%<br>once daily for two consecutive days | Drug: Ingenol once daily for two consecutive days<br> <br> |
| Experimental: Ingenol derivative concentration 1<br>once daily for two consecutive days | Drug: Ingenol once daily for two consecutive days<br> <br> |
| Experimental: Ingenol derivative concentration 2<br>once daily for two consecutive days | Drug: Ingenol once daily for two consecutive days<br> <br> |
| Experimental: Ingenol derivative concentration 3<br>once daily for two consecutive days | Drug: Ingenol once daily for two consecutive days<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of a new ingenol derivative compared to ingenol mebutate 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate treatment responses on Actinic Keratosis of different concentrations of a new ingenol derivative gel compared to the ingenol mebutate gel as assessed by reduction in number of clinically visible selected AK lesions eight weeks after treatment | Assessed by Reflective Confocal Microscopy scoring of visible selected AK lesions | 8 weeks |