Double-blind, Randomized, Vehicle- and Comparator-controlled, Multi-center Trial to Evaluate the Efficacy and Safety of LAS41007 in the Treatment of Actinic Keratosis

The aim of this study is to determine the efficacy, safety and tolerability of LAS41007 compared to a marketed reference product as well as to vehicle (topical application, twice daily, indication mild to moderate AK).

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: LAS41007; Drug: LASW1510; Drug: vehicle of LAS41007

• Study Type: Interventional
• Enrollment (Actual): 889
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Vechta, Germany, 49377
    • Almirall Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have at least 6 but not more than 16 clinically confirmed AK target lesions of mild to moderate (grade I to II, according to Olsen et al., 1991) intensity in the whole treatment area (TA) (and additionally one representative AK lesion for histological diagnosis of AK), which must be located in the face including the forehead (excluding eyelids, lips and mucosa) and/or bald scalp,
• The AK target lesions must be discrete and quantifiable; the distance from one lesion to its neighbor lesion must be greater than 1.0 cm,
• The diameter of each AK target lesion should be not less than 0.5 cm and not greater than 1.5 cm,
• The target lesions must be located in up to 3 TAs with a size of 25 cm2 per TA (i.e. total area of TA is up to 75 cm2),
• Diagnosis of AK histologically confirmed

Exclusion Criteria:

• Have known hypersensitivity, intolerance or allergies against ingredients of the IMPs and other non-steroidal anti-inflammatory agents,
• Have a history of bronchospasm, asthma, urticaria, or rhinitis after the intake of non-steroidal anti-inflammatory drugs (NSAIDs),
• Have a history of gastrointestinal bleeding or perforation associated with prior therapy with NSAIDs,
• Have evidence of clinically significant or unstable medical conditions,
• Have currently and within the past 3 months other malignant tumors of the skin in the TAs,
• Suffer from paresthesia in the TAs,
• Show cornu cutaneum of the skin and/or hypertrophic AK lesions in the TAs,
• Are known to be pregnant or lactating (currently or within the past 3 months),
• Any clinically relevant abnormal finding during Screening and/or Baseline,
• Specific topical treatments in the target area within defined time periods.
• Specific physical treatments in the TAs within defined time periods.
• Specific systemic treatments within defined time periods.
• Patients suffering from AK in locations other than the target areas, receiving any topical AK-therapy throughout the interventional phase of the study until termination of V6,
• Patients who need a permanent therapy with any other NSAID. The use of NSAIDs as "prn" (pro re nata), i.e. to be taken as needed (≤ 3 days at a stretch) and the use of ASA as anticoagulative therapy will be allowed,
• Patients taking methotrexate or sulfonylurea during the interventional phase of the study,
• Anticoagulative therapy, e.g. with cumarines or heparines throughout the interventional phase of the study. Treatment with ASA at a dose not exceeding 100 mg/d and clopidogrel at a dose not exceeding 75 mg/d will be allowed,
• Patients having any significant physical abnormalities in the potential TAs that may cause difficulty with examination or final evaluation,
• Have any dermatological disease in the TAs or surrounding area that may be exacerbated by treatment with topical diclofenac or cause difficulty with examination,
• Physical or mental inability and/or unwillingness to apply the study preparations correctly and to follow the study restrictions and visits,
• Any suspicion of current drug and/or alcohol abuse as assessed by the investigator,
• Anticipated non-availability for study visits / procedures,
• Exposure to an investigational product within the last 3 months,
• Any previous randomization into this trial,
• Patient is institutionalized because of legal or regulatory order,
• Employee of the study site or of the Sponsor's company or the CRO.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LAS41007; All patients will be instructed to apply the IMP twice daily, once in the morning and once in the evening. Per application, not more than 1.5 g of the IMP should be applied, which is sufficient to cover a total area of 75 cm2 (corresponding to 3 single TAs, each with a size of 25 cm²) in maximum. The IMPs will be applied for 90 days in maximum.	Drug: LAS41007; Topical gel, to be applied twice daily (mornings and evenings), for up to 90 days. Generally 0.5 g gel (pea-sized amount of gel) per application will be sufficient to cover an overall area of 25 cm².
Active Comparator: LASW1510; All patients will be instructed to apply the IMP twice daily, once in the morning and once in the evening. Per application, not more than 1.5 g of the IMP should be applied, which is sufficient to cover a total area of 75 cm2 (corresponding to 3 single TAs, each with a size of 25 cm²) in maximum. The IMPs will be applied for 90 days in maximum.	Drug: LASW1510; Topical gel, to be applied twice daily (mornings and evenings), for up to 90 days. Generally 0.5 g gel (pea-sized amount of gel) per application will be sufficient to cover an overall area of 25 cm².
Placebo Comparator: vehicle; All patients will be instructed to apply the IMP twice daily, once in the morning and once in the evening. Per application, not more than 1.5 g of the IMP should be applied, which is sufficient to cover a total area of 75 cm2 (corresponding to 3 single TAs, each with a size of 25 cm²) in maximum. The IMPs will be applied for 90 days in maximum.	Drug: vehicle of LAS41007; Topical gel, to be applied twice daily (mornings and evenings), for up to 90 days. Generally 0.5 g gel (pea-sized amount of gel) per application will be sufficient to cover an overall area of 25 cm².

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
superiority of LAS41007 compared to vehicle	superiority of LAS41007 compared to comparator each assessed by histology to evaluate the histological clearance of one pre-selected target lesion	Day 1
superiority of LAS41007 compared to vehicle	superiority of LAS41007 compared to comparator each assessed by histology to evaluate the histological clearance of one pre-selected target lesion	Day 150

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
superiority of LAS41007 compared to vehicle	improved clinical efficacy of LAS41007 compared to comparator with respect to clinical efficacy	Day 1
superiority of LAS41007 compared to vehicle	improved clinical efficacy of LAS41007 compared to comparator with respect to clinical efficacy	Day 21
superiority of LAS41007 compared to vehicle	improved clinical efficacy of LAS41007 compared to comparator with respect to clinical efficacy	Day 56
superiority of LAS41007 compared to vehicle	improved clinical efficacy of LAS41007 compared to comparator with respect to clinical efficacy	Day 90
superiority of LAS41007 compared to vehicle	improved clinical efficacy of LAS41007 compared to comparator with respect to clinical efficacy	Day 150

Collaborators and Investigators

• Sponsor: Almirall, S.A.
• Investigators: Study Director: Dr. Estrella Estrella Garcia, PhD, Almirall, S.A.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 21, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimate): December 23, 2010

Study Record Updates

• Last Update Posted (Estimate): July 24, 2012
• Last Update Submitted That Met QC Criteria: July 23, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Actinic Keratosis; AK; NMSC
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: H 569 000 - 1004