Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2 days placebo and 2 days drug | Experimental | Placebo and drug |
|
| 1 day placebo and 3 days drug | Experimental | Placebo and drug |
|
| 4 days placebo | Placebo Comparator | Placebo |
|
| 4 days drug | Experimental | Drug |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ingenol mebutate | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
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)
Prior treatment with ingenol mebutate within the selected treatment area
Lesions in the treatment area that have:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Daniel M Siegel, MD, MS | Lond Island Skin Cancer and Dermatologic Surgery | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Island Skin Cancer and Dermatologic Surgery | Smithtown | New York | United States |
Not provided
| Label | URL |
|---|---|
| Clinical Trials at LEO Pharma | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
266 participants were enrolled of which 224 participants were randomized to treatment
Participants were followed for 8 weeks following the first application of investigational medicinal product (IMP) at Day 1 (4-day treatment period including an 8-week follow-up period).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Ingenol 2 Days | Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 2 days and ingenol mebutate gel 0.06% was applied for 2 days for a total 4 consecutive days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Other |
|
| At Week 8 |
| 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. | At Week 8 |
| FG001 |
| Ingenol 3 Days |
Ingenol mebutate gel 0.06% and vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg). Vehicle gel was applied for 1 day and ingenol mebutate gel 0.06% was applied for 3 days for a total 4 consecutive days. |
| FG002 | Ingenol 4 Days | Ingenol mebutate gel 0.06% applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days. |
| FG003 | Vehicle | Vehicle gel applied topically once daily to a contiguous area of approximately 250 cm2 sun-damaged skin on trunk (except chest), or extremities (arm with or without back of hand, or leg) for 4 consecutive days. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Ingenol 2 Days | 2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel |
| BG001 | Ingenol 3 Days | 3 days treatment with ingenol mebutate 0.06% gel and 1 day treatment with vehicle gel |
| BG002 | Ingenol 4 Days | 4 days treatment with ingenol mebutate 0.06% gel |
| BG003 | Vehicle | 4 days treatment with vehicle gel |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The analysis was based on the Full Analysis Set, which was defined as all randomized participants. | Posted | Number | percentage of participants | At Week 8 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The analysis was based on the Full Analysis Set, which was defined as all randomized participants. | Posted | Mean | 95% Confidence Interval | percentage of reduction | At Week 8 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The analysis was based on the Full Analysis Set, which was defined as all randomized participants. | Posted | Number | percentage of participants | At Week 8 |
|
From Day 1 to Week 8 (Day 56)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ingenol 2 Days | 2 days treatment with ingenol mebutate 0.06% gel and 2 days treatment with vehicle gel | 0 | 55 | 3 | 55 | 48 | 55 |
| EG001 | Ingenol 3 Days | 1 day treatment with vehicle gel and 3 days treatment with ingenol mebutate 0.06% gel | 0 | 59 | 5 | 59 | 55 | 59 |
| EG002 | Ingenol 4 Days | 4 days treatment with ingenol mebutate 0.06% gel | 0 | 49 | 4 | 49 | 47 | 49 |
| EG003 | Vehicle | 4 days treatment with vehicle gel | 0 | 61 | 0 | 61 | 7 | 61 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| |
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Application site pruritus | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Application site discomfort | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Bowen's disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| |
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
Prior to submitting or presenting a manuscript relating to the clinical trial to a publisher, reviewer or other outside person, the investigator shall provide to LEO Pharma A/S a copy of all such manuscripts, and LEO Pharma A/S shall have rights to review and comment. Upon the request of LEO Pharma A/S the investigator shall remove any confidential information (other than results generated by the investigator) prior to submitting or presenting the manuscripts.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Manager | LEO Pharma A/S | +45 4494 5888 | disclosure@leo-pharma.com |
| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C486592 | 3-ingenyl angelate |
Not provided
Not provided
Not provided
| Male |
|
| Australia |
|
| Superiority |
| Treatment comparison based on 1000 imputations of AK count at week 8 using a negative binomial regression model with factors treatment and analysis site and with log of baseline AK count as offset. Cochran-Mantel-Haenszel logit estimators were used for comparisons with vehicle due to absence of cleared subject in the vehicle group. Type I error not controlled. | Cochran-Mantel-Haenszel | 0.051 | P-value was adjusted for analysis site using Rubin's pooling methodology after log transformation of RR (relative risk) of each imputation. Complete clearance relative to vehicle group and 2-day group. | Relative risk | 3.51 | 2-Sided | 95 | 1.00 | 12.41 | Relative risk and confidence interval were adjusted for analysis site using Rubin's pooling methodology after log transformation of RR of each imputation. Complete clearance relative to vehicle group and 2-day group. | Superiority |
| Treatment comparison based on 1000 imputations of AK count at week 8 using a negative binomial regression model with factors treatment and analysis site and with log of baseline AK count as offset. Type I error not controlled. Mantel-Haenszel estimators were used. | Mantel Haenszel | 0.25 | P-value was adjusted for analysis site using Rubin's pooling methodology after log transformation of RR (relative risk) of each imputation. Complete clearance relative to vehicle group and 2-day group. | Relative risk | 0.47 | 2-Sided | 95 | 0.13 | 1.68 | Relative risk and confidence interval were adjusted for analysis site using Rubin's pooling methodology after log transformation of RR of each imputation. Complete clearance relative to vehicle group and 2-day group. | Superiority |
4 days treatment with ingenol mebutate 0.06% gel |
| OG003 | Vehicle | 4 days treatment with vehicle gel |
|
|
|
4 days treatment with ingenol mebutate 0.06% gel
| OG003 | Vehicle | 4 days treatment with vehicle gel |
|
|
|