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Efficacy and Safety of Ingenol Mebutate Gel 0.06% When Applied Once Daily for 2, 3 or 4 Consecutive Days to a Treatment Area of Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis

Phase 2
Completed
Conditions
Actinic Keratosis
Interventions
Registration Number
NCT01998984
Lead Sponsor
LEO Pharma
Brief Summary

This is a randomised, double-blind, parallel groups, vehicle controlled, 8-week phase 2 trial. The objective is to evaluate efficacy of ingenol mebutate gel 0.06 % after once daily treatment for 2, 3 or 4 consecutive days compared to vehicle gel

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
266
Inclusion Criteria

Subjects with 5 to 20 clinically typical, visible and discrete AKs within a contiguous area of approximately 250 cm² sun-damaged skin on either trunk (except chest), or extremities

Exclusion Criteria
  • Location of the treatment area (trunk (except chest) or extremities)

    • within 5 cm of an incompletely healed wound,
    • within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)
  • Prior treatment with ingenol mebutate within the selected treatment area

  • Lesions in the treatment area that have:

    • atypical clinical appearance (e.g., hypertrophic,hyperkeratotic or cutaneous horns) and/or,
    • recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2 days placebo and 2 days drugingenol mebutatePlacebo and drug
2 days placebo and 2 days drugPlaceboPlacebo and drug
1 day placebo and 3 days drugingenol mebutatePlacebo and drug
1 day placebo and 3 days drugPlaceboPlacebo and drug
4 days placeboPlaceboPlacebo
4 days drugingenol mebutateDrug
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs)At Week 8

Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in number of AKs.

The table presents the mean across 1000 multiple imputations. Missing values for AK count were imputed sequentially from a negative binomial regression model with treatment group, AK counts at the previous visit, and analysis site as covariates and log baseline AK count as offset.

Secondary Outcome Measures
NameTimeMethod
Percentage of Reduction in Actinic Keratosis (AK) Lesion Count From Baseline (Day 1) (Multiple Imputation)At Week 8

The number of clinically visible AK lesions identified in the treatment area was to be recorded at Visit 1(≤14 days prior to Day 1).

The analysis was based on 1000 imputations of actinic keratosis lesion count at Week 8 using a negative binomial regression model with factors treatment and analysis site and with log of baseline actinic keratosis lesion count as offset. The table shows the adjusted percentage reduction from baseline.

Values for the Ingenol 4 days arm were calculated separately based on observed cases. On the basis of the data monitoring committee's recommendation the 4-day active treatment group was closed, and this arm was excluded from statistical models and comparisons in the secondary efficacy analyses.

Percentage of Participants With Partial Clearance of AKsAt Week 8

Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in number of AKs, was analysed in the same way as the primary response criterion.

The percent reduction at Week 8 from baseline was analyzed using a negative binomial regression for the AK count at Week 8 with treatment group and pooled sites as factors and baseline count as offset variable (using multiple imputations to account for missing values).

The table presents the mean across 1000 multiple imputations. Missing values for AK count were imputed sequentially from a negative binomial regression model with treatment group, AK counts at the previous visit, and analysis site as covariates and log baseline AK count as offset.

Trial Locations

Locations (1)

Long Island Skin Cancer and Dermatologic Surgery

🇺🇸

Smithtown, New York, United States

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