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

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ClinicalTrials.gov Identifier: NCT02242747
Recruitment Status : Completed
First Posted : September 17, 2014
Last Update Posted : September 17, 2014
LEO Pharma
Information provided by (Responsible Party):
Luis Antonio Torezan, University of Sao Paulo

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Actinic Keratosis Drug: ingenol mebutate Drug: 5% 5-FU Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2014
Actual Primary Completion Date : July 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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 Name: Picato

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

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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.

Other Outcome Measures:
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02242747

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Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)
Sao Paulo, Brazil, 05403000
Sponsors and Collaborators
University of Sao Paulo
LEO Pharma
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Principal Investigator: Luis Antonio Torezan, PhD Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Luis Antonio Torezan, Associate Professor University of Sao Paulo, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT02242747    
Other Study ID Numbers: 11334
First Posted: September 17, 2014    Key Record Dates
Last Update Posted: September 17, 2014
Last Verified: September 2014
Keywords provided by Luis Antonio Torezan, University of Sao Paulo:
actinic keratosis
field cancerization
ingenol mebutate
Additional relevant MeSH terms:
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Keratosis, Actinic
Skin Diseases
Precancerous Conditions