A Study to Evaluate the Pharmacokinetics of PEP005 (Ingenol Mebutate) Gel, 0.05%, When Applied in a Maximal Use Setting to the Dorsal Aspect of the Forearm in Patients With Actinic Keratosis

Study Overview
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Brief Summary
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This Phase II study is designed to evaluate the pharmacokinetics of PEP005 (ingenol mebutate) Gel, 0.05% when applied in a maximal use setting to the dorsal aspect of the forearm in patients with actinic keratoses

Official Title
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A Randomized, Double-blind, Vehicle-controlled Study to Evaluate the Pharmacokinetics of PEP005 (Ingenol Mebutate) Gel, 0.05%, When Applied in a Maximal Use Setting to the Dorsal Aspect of the Forearm in Patients With Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: PEP005 (ingenol mebutate) Gel, 0.05%
* Drug: Vehicle Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female; Multiple actinic keratosis (AK) lesions over a 100 cm^2 area of skin located on the dorsal aspect of one forearm. Exclusion Criteria: Cosmetic or therapeutic procedures: within 2 weeks and within 2 cm of the selected treatment area(s); Treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system: within 4 weeks; Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 8 weeks and within 2 cm of the selected treatment area(s).

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEP005 (ingenol mebutate) Gel, 0.05%<br> | Drug: PEP005 (ingenol mebutate) Gel, 0.05%<br>* PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days<br>|
| Placebo Comparator: Vehicle Gel<br> | Drug: Vehicle Gel<br>* Vehicle Gel once daily for 2 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | Maximum observed concentration (Cmax) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels over the 24 hour sampling time period based on actual values measured. Blood samples were taken: at 30 minutes, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. | 1 day | 
| Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels. | Time at which Cmax is attained (Tmax) for ingenol mebutate, and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. If a maximum value occured at more than one timepoint Tmax is defined as the first timepoint with this value. | 1 day | 
| Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | Area under the blood conc. versus time curve was calculated for time 0-24 hours (AUC(0-24)) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area | Number of participants with complete clearence. Complete clearance rate is defined as no clinically visible actinic keratosis (AK) lesions in a 25 cm^2 area within the selected treatment area at Day 57 compared to baseline | baseline and day 57 | 
| Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area | Percentage (%) change in actinic keratosis (AK) lesions count at Day 57, compared to baseline, in a 25 cm^2 area within the selected treatment area. | Baseline and Day 57 | 
| Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study. | Number of patients with LSR at any time point during the study above 0. The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. | baseline and Day 2, 3, 8, 15, 29 and 57 | 
| Patients With Incidence of Pigmentation and Scarring | Patients with Incidence of pigmentation and scarring, and grade of pigmentation and scarring, following study treatment through Day 57 | Baseline, Day 2, 3, 8, 15, 29 and 57 | 
| Max Composite Local Skin Response (LSR) Score | Max composite Local Skin Response (LSR) score on day 3 only . The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. (One vehicle treated patent had a LSR on day 1 only). | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peplin, PEP005, Actinic Keratosis