Back to results

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

Primary Purpose

Actinic Keratosis

Status

Completed

Phase

Not Applicable

Locations

Brazil

Study Type

Interventional

Intervention

ingenol mebutate

5% 5-FU

About this trial

This is an interventional treatment trial for Actinic Keratosis focused on measuring actinic keratosis, field cancerization, ingenol mebutate, 5-fluorouracil, tolerability, safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

ingenol mebutate

5% 5-FU

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02242747

First Posted

September 12, 2014

Last Updated

September 15, 2014

Sponsor

University of Sao Paulo

Collaborators

LEO Pharma

1. Study Identification

Unique Protocol Identification Number

NCT02242747

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Completed

Study Start Date

May 2014 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Sao Paulo

Collaborators

LEO Pharma

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Actinic Keratosis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ingenol mebutate

Arm Type

Other

Arm Description

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

Arm Title

5% 5-FU

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

ingenol mebutate

Other Intervention Name(s)

Picato

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

5% 5-FU

Other Intervention Name(s)

efurix, efudex

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and on day 43

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and on day 43

Other Pre-specified Outcome Measures:

Title

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

Description

An additional endpoint was to evaluate adverse effects related to the drugs.

Time Frame

Baseline and on day 43

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Luis Antonio Torezan, PhD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Sao Paulo

ZIP/Postal Code

05403000

Country

Brazil

12. IPD Sharing Statement

Citations:

PubMed Identifier

25727104

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs