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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

PEP005 (ingenol mebutate) Gel, 0.05%

Vehicle Gel

About this trial

This is an interventional treatment trial for Actinic Keratosis focused on measuring Peplin, PEP005, Actinic Keratosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

DermResearch, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PEP005 (ingenol mebutate) Gel, 0.05%

Vehicle Gel

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

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

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.

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.

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

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).

Full Information

NCT ID

NCT00852137

First Posted

February 22, 2009

Last Updated

February 18, 2015

Sponsor

Peplin

1. Study Identification

Unique Protocol Identification Number

NCT00852137

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2012

Overall Recruitment Status

Completed

Study Start Date

March 2009 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Peplin

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Actinic Keratosis

Keywords

Peplin, PEP005, Actinic Keratosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PEP005 (ingenol mebutate) Gel, 0.05%

Arm Type

Experimental

Arm Title

Vehicle Gel

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

PEP005 (ingenol mebutate) Gel, 0.05%

Intervention Description

PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days

Intervention Type

Drug

Intervention Name(s)

Vehicle Gel

Intervention Description

Vehicle Gel once daily for 2 consecutive days

Primary Outcome Measure Information:

Title

Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels

Description

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.

Time Frame

1 day

Title

Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels.

Description

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.

Time Frame

1 day

Title

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

Description

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.

Time Frame

1 day

Secondary Outcome Measure Information:

Title

Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area

Description

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

Time Frame

baseline and day 57

Title

Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area

Description

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.

Time Frame

Baseline and Day 57

Title

Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study.

Description

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.

Time Frame

baseline and Day 2, 3, 8, 15, 29 and 57

Title

Patients With Incidence of Pigmentation and Scarring

Description

Patients with Incidence of pigmentation and scarring, and grade of pigmentation and scarring, following study treatment through Day 57

Time Frame

Baseline, Day 2, 3, 8, 15, 29 and 57

Title

Max Composite Local Skin Response (LSR) Score

Description

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).

Time Frame

Day 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Jarratt, MD

Organizational Affiliation

Derm Research, PLLC

Official's Role

Principal Investigator

Facility Information:

Facility Name

DermResearch, Inc.

City

Austin

State/Province

Texas

ZIP/Postal Code

78759

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25584134

Citation

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.

Results Reference

derived

Links:

URL

http://www.fda.gov

Description

Food and Drug Authority

Actinic Keratosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial