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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Peplin
ClinicalTrials.gov Identifier:
NCT00852137
First received: February 22, 2009
Last updated: April 24, 2012
Last verified: April 2012
  Purpose

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


Condition Intervention Phase
Actinic Keratosis
Drug: PEP005 (ingenol mebutate) Gel, 0.05%
Drug: Vehicle Gel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Peplin:

Primary Outcome Measures:
  • Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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 Frame: 1 day ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Day 57 ] [ Designated as safety issue: No ]
    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. [ Time Frame: baseline and Day 2, 3, 8, 15, 29 and 57 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, Day 2, 3, 8, 15, 29 and 57 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 16
Study Start Date: March 2009
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00852137

Locations
United States, Texas
DermResearch, Inc.
Austin, Texas, United States, 78759
Sponsors and Collaborators
Peplin
Investigators
Principal Investigator: Michael Jarratt, MD DermResearch, Inc
  More Information

Additional Information:
No publications provided

Responsible Party: Peplin
ClinicalTrials.gov Identifier: NCT00852137     History of Changes
Other Study ID Numbers: PEP005-017
Study First Received: February 22, 2009
Results First Received: February 21, 2012
Last Updated: April 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Peplin:
Peplin
PEP005
Actinic Keratosis

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms

ClinicalTrials.gov processed this record on April 16, 2014