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

Actinic Keratosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02242747
• Other study ID #: 11334
• Status: Completed
• Phase: N/A
• First received: September 12, 2014
• Last updated: September 15, 2014
• Start date: May 2014
• Est. completion date: August 2014

Study information

• Verified date: September 2014
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• ingenol mebutate
an application a day for three consecutive days in a pre-determined area
• 5% 5-FU
two applications a day for four weeks in a pre-determined area

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP)	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	LEO Pharma

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with side effects in each arm of the study	An additional endpoint was to evaluate adverse effects related to the drugs.	Baseline and on day 43	Yes
Primary	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	Yes
Secondary	Area Under the each component of the total LSR-Time Curve (AUC 0-43 days)	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	Yes