Safety and Tolerability Study of Ingenol Mebutate Compared to 5-FU to Treat Facial Actinic Keratosis

September 15, 2014 updated by: Luis Antonio Torezan, University of Sao Paulo

Evaluation of the Tolerability and Safety of 0.015% Ingenol Mebutate Gel Compared to 5% 5-fluorouracil Cream for the Treatment of Facial Actinic Keratosis: a Prospective Randomized Trial

Background: 5% 5-fluorouracil cream (5-FU) is a well-established treatment for actinic keratosis (AK) and ingenol mebutate gel (IMB) is a new topical field therapy.

Objective: To compare tolerability and safety of IMB with 5-FU for the treatment of facial AKs.

Methods: Open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within 25-cm2 contiguous field on the face. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for four weeks. Treatment effect was evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43, considering ITT populations.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil, 05403000
        • Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • age of at least 18 years
  • the presence of four to eight clinically typical, visible, and discrete AKs within 25-cm2 contiguous field on the face (cheek or forehead region)
  • Women with childbearing potential had to be using effective birth control and have a confirmed negative urine pregnancy test prior to trial treatment.

Exclusion Criteria:

  • target treatment area was within 5 cm of an incompletely healed wound or within 10 cm of a suspected basal-cell or squamous-cell carcinoma
  • if they have received previous treatment with ingenol mebutate gel on the face or scalp (previous treatment on trunk or extremities was acceptable)
  • the selected treatment area had hyperkeratotic lesions or cutaneous horns and recalcitrant disease (lesions that had not responded to cryotherapy on two previous occasions)
  • history or evidence of skin conditions that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
  • anticipated need for hospitalization or outpatient surgery during the first 15 days after the first trial medication application
  • known sensitivity or allergy to any of the ingredients of ingenol mebutate gel or 5-FU
  • presence of sunburn within of the target treatment area; current enrolment or participation in any other interventional clinical trial within 30 days of entry into this trial
  • women breastfeeding
  • recent use of medications or other treatments that could interfere with evaluation of the target area, such as topical medications (e.g. steroids, keratolytics, immunomodulators), artificial tanners, immunomodulators, cytotoxic drugs or interferon /interferon inducers, phototherapy, systemic retinoids, biologic/monoclonal antibody drugs, or other therapies for AKs within eight weeks prior to the first visit of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: ingenol mebutate
Patients assigned to ingenol mebutate gel received an application a day for three consecutive days in a pre-determined area
Drug: ingenol mebutate
an application a day for three consecutive days in a pre-determined area
Other Names:
  • Picato
Other: 5% 5-FU
Patients assigned to 5% 5-FU received two applications a day for four weeks in a pre-determined area
Drug: 5% 5-FU
two applications a day for four weeks in a pre-determined area
Other Names:
  • efurix
  • efudex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the LSR (local skin reactions)-Time Curve (AUC 0-43 days)
Time Frame: Baseline and on day 43
Primary endpoint was to compare the total local skin reaction grading scale (LSR) and the area under the curve (AUC) with respect to duration of effects, using a generalized linear model, assuming a logarithmic link function. Age, Fitzpatrick skin type and site of the treatment were considered as covariates. The scale ranged from 0 to 4 (with higher numbers indicating greater severity) for the following six local skin effects: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration (maximum score of 24).
Baseline and on day 43

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)
Time Frame: Baseline and on day 43
A secondary endpoint was to evaluate and compare the AUC for each component of the total LSR using generalized linear models. The effect of treatment on the proportion of patients that completed the assigned treatment regimens was compared using generalized estimating equation model and logarithmic link function.
Baseline and on day 43

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with side effects in each arm of the study
Time Frame: Baseline and on day 43
An additional endpoint was to evaluate adverse effects related to the drugs.
Baseline and on day 43

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

LEO Pharma

Investigators

  • Principal Investigator: Luis Antonio Torezan, PhD, Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

September 12, 2014

First Submitted That Met QC Criteria

September 15, 2014

First Posted (Estimate)

September 17, 2014

Study Record Updates

Last Update Posted (Estimate)

September 17, 2014

Last Update Submitted That Met QC Criteria

September 15, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11334 (DAIDS ES)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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