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

NCT02242747 | Completed DMC

• 1 other identifier: 11334
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Actinic Keratosis

Keywords

actinic keratosis; field cancerization; ingenol mebutate; 5-fluorouracil; tolerability; safety

Outcome Measures

Primary Outcomes (1)

• Area under the LSR (local skin reactions)-Time Curve (AUC 0-43 days)

  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 Outcomes (1)

• Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)

  Baseline and on day 43

Other Outcomes (1)

• Number of participants with side effects in each arm of the study

  Baseline and on day 43

Study Arms (2)

ingenol mebutate

OTHER

Patients assigned to ingenol mebutate gel received an application a day for three consecutive days in a pre-determined area

Drug: ingenol mebutate

5% 5-FU

OTHER

Patients assigned to 5% 5-FU received two applications a day for four weeks in a pre-determined area

Drug: 5% 5-FU

Interventions

ingenol mebutate DRUG

an application a day for three consecutive days in a pre-determined area

Also known as: Picato

ingenol mebutate

5% 5-FU DRUG

two applications a day for four weeks in a pre-determined area

Also known as: efurix, efudex

5% 5-FU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Sao Paulo: lead
• LEO Pharma: collaborator

Study Sites (1)

Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)

São Paulo, São Paulo, 05403000, Brazil

Location

Related Publications (1)

• Samorano LP, Torezan LA, Sanches JA. Evaluation of the tolerability and safety of a 0.015% ingenol mebutate gel compared to 5% 5-fluorouracil cream for the treatment of facial actinic keratosis: a prospective randomized trial. J Eur Acad Dermatol Venereol. 2015 Sep;29(9):1822-7. doi: 10.1111/jdv.13063. Epub 2015 Feb 27.

  PMID: 25727104 DERIVED

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

3-ingenyl angelate; Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Luis Antonio Torezan, PhD

  Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor University of Sao Paulo

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 17, 2014
• Study Start: May 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 17, 2014

Record last verified: 2014-09

Locations

BR (1)