Back to resultsEfficacy 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
Primary Purpose
Actinic Keratosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ingenol mebutate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Actinic Keratosis
Eligibility Criteria
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)
Sites / Locations
- Long Island Skin Cancer and Dermatologic Surgery
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
2 days placebo and 2 days drug
1 day placebo and 3 days drug
4 days placebo
4 days drug
Arm Description
Placebo and drug
Placebo and drug
Placebo
Drug
Outcomes
Primary Outcome Measures
Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs)
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
Percentage of Reduction in Actinic Keratosis (AK) Lesion Count From Baseline (Day 1) (Multiple Imputation)
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 AKs
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01998984
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LEO Pharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Actinic Keratosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
266 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2 days placebo and 2 days drug
Arm Type
Experimental
Arm Description
Placebo and drug
Arm Title
1 day placebo and 3 days drug
Arm Type
Experimental
Arm Description
Placebo and drug
Arm Title
4 days placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
4 days drug
Arm Type
Experimental
Arm Description
Drug
Intervention Type
Drug
Intervention Name(s)
ingenol mebutate
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs)
Description
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.
Time Frame
At Week 8
Secondary Outcome Measure Information:
Title
Percentage of Reduction in Actinic Keratosis (AK) Lesion Count From Baseline (Day 1) (Multiple Imputation)
Description
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.
Time Frame
At Week 8
Title
Percentage of Participants With Partial Clearance of AKs
Description
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.
Time Frame
At Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel M Siegel, MD, MS
Organizational Affiliation
Lond Island Skin Cancer and Dermatologic Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Long Island Skin Cancer and Dermatologic Surgery
City
Smithtown
State/Province
New York
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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