A Study of Increasing Strengths, Safety and Efficacy of Two Formulas of LEO 43204 on the Face or the Chest in Patients With Actinic Keratosis

Actinic Keratosis Clinical Trial

Official title:

Safety and Efficacy of Escalating Doses of Two LEO 43204 Formulations Applied Once Daily for Two Consecutive Days on Full Face or Approximately 250 cm2 (40 in2) on the Chest in Subjects With Actinic Keratosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01922050
• Other study ID #: LP0084-1013
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2013
• Est. completion date: November 2014

Study information

• Verified date: February 2019
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Part 1:

To identify Maximum Tolerated Dose (MTD) levels of two formulations of LEO 43204 after once daily treatment for two consecutive days

Part 2:

To evaluate efficacy of two formulations of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle formulations

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Following verbal and written information about the trial, subject must provide informed consent documented by signing the Informed Consent Form (ICF) prior to any trial-related procedures.

2. Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face

3. Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face or within a contiguous area of approximately 250 cm2 (40 in2) on the chest

4. Subject at least 18 years of age.

5. Female subjects must be of either:

1. Non-childbearing potential, i.e., have a confirmed clinical history of sterility (e.g., the subject is without a uterus or have tubal ligation), or,

2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment.

6. Female subjects of childbearing potential must use effective contraception throughout the study.

Exclusion Criteria:

1. Location of the treatment area within 5 cm (2 inches) of:

1. an incompletely healed wound,

2. a suspected basal or squamous cell carcinoma.

2. Prior treatment with ingenol mebutate gel on the treatment area.

3. Lesions in the treatment areas that have:

1. atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or

2. recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions).

4. History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum, Rosacea), at the investigator's discretion.

5. Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.

6. Any other disease or medical condition such as history or presence of cancer, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunological, or neurological disease or disorder, that, in the opinion of the investigator, makes the subject unsuitable to participate in the trial.

7. Any abnormal laboratory or ECG findings that are clinically significant and would impact the safety of the subjects or the interpretation of the study results, as determined by the investigator.

8. Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications.

9. Known sensitivity or allergy to any of the ingredients in the LEO 43204.

10. Presence of acute sunburn within the treatment areas.

11. Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.

12. Subjects previously randomised in the trial (Part 1 or 2).

13. Female subjects who are breastfeeding.

14. In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g., alcoholism, drug dependency or psychotic state).

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• LEO 43204 Formulation 1

• LEO 43204 Formulation 2

• LEO 43204 Formulation 1 Dose X

• LEO 43204 Formulation 1 Dose Y

• LEO 43204 Formulation 2 Dose XX

• LEO 43204 Formulation 2 Dose YY

• Placebo Formulation 1

• Placebo Formulation 2

Locations

Country	Name	City	State
Canada	Ultranova Skincare	Barrie	Ontario
Canada	Co-Medica Research Network Inc.	Courtice	Ontario
Canada	Stratica Medical Inc.	Edmonton	Alberta
Canada	Dermatrials Research Incorporated	Hamilton	Ontario
Canada	The Guenther Dermatology Research Centre	London	Ontario
Canada	Lynderm Research Inc.	Markham	Ontario
Canada	Durondel C.P. Inc./Dermatology Clinic	Moncton	New Brunswick
Canada	SKiN Centre for Dermatology	Peterborough	Ontario
Canada	Centre de Recherche Dermatologique du Quebec Metropolitain	Quebec City	Quebec
Canada	Guildford Dermatology Specialists	Surrey	British Columbia
Canada	K. Papp Clinical Research	Waterloo	Ontario
Canada	XLR8 Medical Research	Windsor	Ontario
United States	Great Lakes Research Group, Inc.	Bay City	Michigan
United States	Hudson Dermatology, LLC	Evansville	Indiana
United States	Research Institute of Deaconess Clinic	Evansville	Indiana
United States	Torrance Clinical Research Institute Inc.	Lomita	California
United States	Mount Sinai School of Medicine	New York	New York
United States	Leavitt Medical Associates of Florida	Ormond Beach	Florida
United States	Omni Dermatology	Phoenix	Arizona
United States	DermAssociates, PC	Rockville	Maryland
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.	San Diego	California
United States	Clinical Research Center, Morsani Center for Advanced Healthcare	Tampa	Florida
United States	The Dermatology Group, P.C.	Verona	New Jersey
United States	Henry Ford Medical Center, Dept. of Dermatology	West Bloomfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)	The number of participants experiencing DLTs are tabulated by treatment group. This was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants(cohorts 1 to 4) or less than 6 out of 18 participants(cohorts 5 and 6) experiencing a DLT; DLT was defined as one or more of the following 3 LSRs: Crusting Grade 4; Erosion/Ulceration Grade 4; Vesiculation/Pustulation Grade 4; or two or more of the following five LSRs: Erythema Grade 4; Crusting Grade 3; Swelling Grade 4; Erosion/Ulceration Grade 3; Vesiculation/Pustulation Grade 3; The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and 4 being the highest grade of severity.	From Day 1 up to and including Day 8
Primary	Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Counts (Multiple Imputation)		At Week 8
Secondary	Part 2: Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs) (Multiple Imputation)	Complete clearance was defined as a 100% reduction from baseline in AK count. For treatment groups Vehicle, 0.006 and 0.012 the table shows the percentage of mean number of participants across imputations with complete clearance. For treatment group 0.018 the table shows the percentage of mean number of participants with complete clearance in observed cases.	At Week 8
Secondary	Part 2: Percentage of Participants With Partial Clearance of AKs (Multiple Imputation)	Partial clearance was defined as at least 75% reduction from baseline in AK count.; For treatment groups Vehicle, 0.006 and 0.012 the table shows the percentage of mean number of participants across imputations with partial clearance. For treatment group 0.018 the table shows the percentage of mean number of participants with partial clearance in observed cases.	At Week 8