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

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

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

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: PEP005 (ingenol mebutate) Gel, 0.05%; Drug: Vehicle Gel

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78759
      • Dermresearch, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PEP005 (ingenol mebutate) Gel, 0.05%	Drug: PEP005 (ingenol mebutate) Gel, 0.05%; PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
PLACEBO_COMPARATOR: Vehicle Gel	Drug: Vehicle Gel; Vehicle Gel once daily for 2 consecutive days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peplin

Publications and helpful links

General Publications

• Anderson L, Jarratt M, Schmieder G, Shumack S, Katsamas J, Welburn P. Tolerability and Pharmacokinetics of Ingenol Mebutate 0.05% Gel Applied to Treatment Areas up to 100cm(2) on the Forearm(s) of Patients with Actinic Keratosis. J Clin Aesthet Dermatol. 2014 Dec;7(12):19-29.

Helpful Links

• Food and Drug Authority

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): June 1, 2009
• Study Completion (ACTUAL): June 1, 2009

Study Registration Dates

• First Submitted: February 22, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (ESTIMATE): February 26, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 6, 2015
• Last Update Submitted That Met QC Criteria: February 18, 2015
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Actinic Keratosis; Peplin; PEP005
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: PEP005-017