Actinic Keratosis
Conditions
Keywords
Korean
Brief summary
This study evaluate the efficacy and safety of ingenol mebutate gel 0.015% on face and scalp & 0.05% on trunk and extremities in Korean patient with actinic keratosis.
Detailed description
The mechanism of action of ingenol mebutate for actinic keratosis(AK) treatment involves a rapid induction of necrosis followed by neutrophil-mediated, antibody-dependent cellular cytotoxicity (ADCC) of residual lesion. As the ingenol mebutate infiltrates the cell membrane, it increases intracellular Ca2+ concentration which leads to mitochondrial swelling and disruption of mitochondrial membrane within hours. The release of intra-mitochondrial Ca2+ into the cytoplasm leads to depletion of adenosine triphosphate (ATP) and a rapid induction of cell death by necrosis. This process occurs within 1 hour of application, which explains why the treatment period requires only 2 or 3 days of treatment. As the next phase, the cellular necrosis is accompanied by a robust inflammatory response through the release of proinflammatory cytokines from skin cells and tumor cells undergoing necrosis. The release of these proinflammatory cytokines into the dysplastic cells mediates the process of neutrophil recruitment through paracrine signaling and activation of endothelial cells. Here, the neutrophil mediated ADCC occurs, where activated neutrophils attach to the fragment, crystallized (Fc) parts of antibodies of dysplastic cells and destroys the residual dysplastic epidermal cells. In this way, the ingenol mebutate eradicates any residual tumor cells and prevents recurrence of actinic keratosis.As described above, the rapid effect and dual mechanism of action of ingenol mebutate gel allows not only a short-course therapy (2 or 3 days of application) for the elimination of actinic keratosis but also, the benefit for eradication of any residual lesions preventing the recurrence and the progression of AK into squamous cell carcinoma (SCC).
Interventions
-Face or Scalp arm (Referred to Face/Scalp arm): Apply ingenol mebutate gel 0.015% once daily for 3 consecutive days
-Trunk or Extremities arm (Referred to Trunk/Extremities arm): Apply ingenol mebutate gel 0.05% once daily for 2 consecutive days
Sponsors
LEO Pharma
Chonnam National University Hospital
Severance Hospital
Ajou University School of Medicine
Asan Medical Center
Samsung Medical Center
Seoul National University Bundang Hospital
Dong-A University Hospital
Korea University Anam Hospital
Seoul National University Hospital
Korea University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥ 19 years 2. Histopathologically diagnosed AK patients with at least 1 macroscopic and discrete lesion within a contiguous 25 cm2 (e.g. 5 cm x 5 cm) of treatment area 3. The treatment area including the lesion must be accessible to apply the investigational product. However, the lesions on lips, mucosa, outer ear (concha) and those around eyes are excluded. 4. Subjects who signed the written informed consent prior to perform any study-related procedures or assessments, including photographs of their treatment area for documentation and efficacy assessment.
Exclusion criteria
1. Hypersensitivity to any components of the investigational product 2. History or evidence of skin conditions that could interfere with evaluation of the investigational product(e.g., eczema, unstable psoriasis, xeroderma pigmentosa, inflammatory or infectious disease around the selected treatment area) 3. Unhealed wound within 5 cm, or basal cell carcinoma or squamous cell carcinoma within 10 cm from the selected treatment area. 4. Subjects who received or expected to receive any of the following pharmacotherapy and non-pharmacotherapy or procedures during the treatment and follow-up period 5. Subjects who have following disorder or abnormal laboratory result 6. Pregnant, lactating, and childbearing potential women who are unwilling to practice effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and abstinence. 7. Subjects who previously underwent another clinical trial within 30 days or 5-times the half-life of previous investigational product prior to baseline (the longer period of time must be considered). 8. Other conditions by investigator's discretion to be inappropriate for this clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CC Rate of AK Lesions in the Selected Treatment Area | at day 57 | Complete Clearance (CC) means that clearance of all visible AK lesions in the selected treatment area and Investigator-rated actinic keratiosis(AK) lesion complete clearance (CC) rate at the selected treatment area on day 57 was analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change of the Number of AK Lesions in the Selected Treatment Area | Baseline and Day 57 | Percentage change from baseline in the number of actinic keratiosis(AK) lesions in the selected treatment area on Day 57 was analyzed. |
| Sustained CC Rate in CC Group | at 6 months | Sustained Complete Clearance means that Complete Clearance was maintained until Month 6 in complete clearance (CC) group and sustained complete clearance(CC) rate at month 6 for complete clearance(CC) group was analyzed. |
| Recurrence Rate in CC Group | at 6 months | Recurrence rate in complete clearance(CC) group was analyzed. |
| Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group | at 6 months from baseline | Percentage change from baseline in the number of actinic keratiosis(AK) lesions at Month 6 in the selected treatment area in complete clearance(CC) Group was analyzed. |
| Cosmetic Outcomes Assessment (COA) | at 29 and 57 days from baseline | The investigator rated the subject's Cosmetic Outcomes Assessment(COA) using 5 grades (Very good, Good, No change, Bad, Very bad), and results were as follows. |
| Time to Relapse in CC Group | at 6 months | Time to relapse in complete clearance(CC) Group was analyzed. Median survival time with 95% confidence interval was calculated by Kaplan-Meier method. |
| Change From Baseline in Quality of Life (Skindex-29) | at 29 and 57 days from baseline | Skindex-29 is a self-administered QoL questionnaire comprised of 29 items scored on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, 4=all the time) covering 3 domains: emotional (10 items), symptomatic (7 items), and functional (12 items), with domain scores ranging from 0 to 40, 28, and 48, respectively. Lower scores for each of the domains represents a better Quality of life. |
| Treatment Satisfaction Questionnaire for Medication (TSQM) | at 29 and 57 days from baseline | Participants personally completed the tool to evaluate satisfaction with drug treatment. It consisted of 4 areas of Effectiveness, side effect, convenience, and global satisfaction, with a total of 14 sub-items. The full mark is 100, and it is divided in four stages as follows. * Very good: 76 -100 score * Good: 51-75 score * Not bad: 26-50 score * Bad: 0-25 score Scores for each area ranged from 0 to 100, with higher scores indicating that fewer side effects had occurred and greater treatment satisfaction. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Medication for Actinic Keratosis | from 57 days to 6 months | The count of participants in complete clearance(CC) group and Non-CC group who administered medication for actinic keratosis on the selected treatment area after Day 57 was collected. |
| Non-Drug Treatment/Surgery for Actinic Keratosis | from 57 days to 6 months | The count of participants in complete clearance(CC) group and Non-CC group who received non-drug treatment/surgery for actinic keratosis on the selected treatment area after Day 57 was collected. |
Countries
South Korea
Participant flow
Recruitment details
This study enrolled patients with actinic keratosis (AK) patients with the lesions on the face, scalp, trunk and/or extremities from 10 academic medical centers in South Korea. First subject was enrolled on 06 Apr 2015 and Last subject was completed on 13 Jun 2016.
Participants by arm
| Arm | Count |
|---|---|
| Ingenol Mebutate Gel 0.015% Participants with actinic keratosis on the face or scalp received 1 tube of ingenol mebutate gel 0.015% to be self-applied to the selected treatment area once daily for 3 consecutive days.
1 tube (0.47g) contained the amount that can be applied to the area of approximately 25cm2(eg. cn. 5cm X 5cm) and 1 tube was applied to the selected treatment area. | 64 |
| Ingenol Mebutate Gel 0.05% Participants with actinic keratosis on the trunk or extremities received 1 tube of ingenol mebutate gel 0.05% to be self-applied to the selected treatment area once daily for 2 consecutive days.
1 tube (0.47g) contained the amount that can be applied to the area of approximately 25cm2(eg. cn. 5cm X 5cm) and 1 tube was applied to the selected treatment area. | 9 |
| Total | 73 |
Baseline characteristics
| Characteristic | Ingenol Mebutate Gel 0.015% | Total | Ingenol Mebutate Gel 0.05% |
|---|---|---|---|
| Actinic keratosis duration | 8.43 months STANDARD_DEVIATION 26.73 | 9.74 months STANDARD_DEVIATION 30.72 | 19.10 months STANDARD_DEVIATION 52.48 |
| Actinic keratosis duration at the selected treatment area | 2.03 months STANDARD_DEVIATION 8.67 | 1.91 months STANDARD_DEVIATION 8.14 | 1.03 months STANDARD_DEVIATION 1.78 |
| Age, Continuous | 72.39 years STANDARD_DEVIATION 8.85 | 72.36 years STANDARD_DEVIATION 8.47 | 72.11 years STANDARD_DEVIATION 5.44 |
| BMI | 22.62 kg/m^2 STANDARD_DEVIATION 2.59 | 22.73 kg/m^2 STANDARD_DEVIATION 2.6 | 23.49 kg/m^2 STANDARD_DEVIATION 2.63 |
| Fitzpatrick skin type I | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick skin type II | 7 Participants | 8 Participants | 1 Participants |
| Fitzpatrick skin type III | 42 Participants | 48 Participants | 6 Participants |
| Fitzpatrick skin type IV | 15 Participants | 17 Participants | 2 Participants |
| Fitzpatrick skin type V | 0 Participants | 0 Participants | 0 Participants |
| Fitzpatrick skin type VI | 0 Participants | 0 Participants | 0 Participants |
| Height | 157.64 cm STANDARD_DEVIATION 7.72 | 157.92 cm STANDARD_DEVIATION 7.51 | 159.89 cm STANDARD_DEVIATION 5.75 |
| Prior treatment history of actinic keratosis No | 52 Participants | 58 Participants | 6 Participants |
| Prior treatment history of actinic keratosis Yes | 12 Participants | 15 Participants | 3 Participants |
| Severity of actinic keratosis AK III (Severe) | 13 Participants | 14 Participants | 1 Participants |
| Severity of actinic keratosis AK II (Moderate) | 42 Participants | 47 Participants | 5 Participants |
| Severity of actinic keratosis AK I (Mild) | 9 Participants | 12 Participants | 3 Participants |
| Sex: Female, Male Female | 46 Participants | 50 Participants | 4 Participants |
| Sex: Female, Male Male | 18 Participants | 23 Participants | 5 Participants |
| Weight | 56.42 kg STANDARD_DEVIATION 8.89 | 56.89 kg STANDARD_DEVIATION 8.93 | 60.24 kg STANDARD_DEVIATION 8.98 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 10 |
| other Total, other adverse events | 67 / 67 | 10 / 10 |
| serious Total, serious adverse events | 1 / 67 | 0 / 10 |
Outcome results
Primary
CC Rate of AK Lesions in the Selected Treatment Area
Complete Clearance (CC) means that clearance of all visible AK lesions in the selected treatment area and Investigator-rated actinic keratiosis(AK) lesion complete clearance (CC) rate at the selected treatment area on day 57 was analyzed.
Time frame: at day 57
Population: Intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | CC Rate of AK Lesions in the Selected Treatment Area | CC | 49 Participants |
| Ingenol Mebutate Gel 0.015% | CC Rate of AK Lesions in the Selected Treatment Area | Non-CC | 15 Participants |
| Ingenol Mebutate Gel 0.05% | CC Rate of AK Lesions in the Selected Treatment Area | CC | 8 Participants |
| Ingenol Mebutate Gel 0.05% | CC Rate of AK Lesions in the Selected Treatment Area | Non-CC | 1 Participants |
Secondary
Change From Baseline in Quality of Life (Skindex-29)
Skindex-29 is a self-administered QoL questionnaire comprised of 29 items scored on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, 4=all the time) covering 3 domains: emotional (10 items), symptomatic (7 items), and functional (12 items), with domain scores ranging from 0 to 40, 28, and 48, respectively. Lower scores for each of the domains represents a better Quality of life.
Time frame: at 29 and 57 days from baseline
Population: Intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 57-Baseline) | 1.45 units on a scale | Standard Deviation 15.6 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Baseline) | 20.57 units on a scale | Standard Deviation 20.62 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 29) | 21.21 units on a scale | Standard Deviation 20.24 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 57) | 15.28 units on a scale | Standard Deviation 19.18 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 29-Baseline) | -0.42 units on a scale | Standard Deviation 21.96 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 57-Baseline) | -6.46 units on a scale | Standard Deviation 18.62 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Baseline) | 16.45 units on a scale | Standard Deviation 17.54 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 29) | 20.16 units on a scale | Standard Deviation 17.52 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 57) | 12.41 units on a scale | Standard Deviation 14.86 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 29-Baseline) | 3.09 units on a scale | Standard Deviation 22.15 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 57-Baseline) | -4.76 units on a scale | Standard Deviation 19.71 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Baseline) | 8.54 units on a scale | Standard Deviation 13.64 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 29) | 17.10 units on a scale | Standard Deviation 20.19 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 57) | 10.58 units on a scale | Standard Deviation 16.97 |
| Ingenol Mebutate Gel 0.015% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 29-Baseline) | 8.02 units on a scale | Standard Deviation 21.32 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 57-Baseline) | -10.19 units on a scale | Standard Deviation 14.67 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 57) | 12.70 units on a scale | Standard Deviation 14.19 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Baseline) | 27.22 units on a scale | Standard Deviation 19.94 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 29) | 5.56 units on a scale | Standard Deviation 7.29 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 29) | 12.50 units on a scale | Standard Deviation 11.59 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 29-Baseline) | -17.46 units on a scale | Standard Deviation 17.08 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 57) | 12.78 units on a scale | Standard Deviation 16.56 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 29-Baseline) | -7.87 units on a scale | Standard Deviation 14.08 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 29-Baseline) | -14.72 units on a scale | Standard Deviation 20.17 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 57-Baseline) | -18.65 units on a scale | Standard Deviation 19.62 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Emotions(Day 57-Baseline) | -14.44 units on a scale | Standard Deviation 20.49 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Day 57) | 3.24 units on a scale | Standard Deviation 7.52 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Baseline) | 31.35 units on a scale | Standard Deviation 18.45 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Functioning(Baseline) | 13.43 units on a scale | Standard Deviation 11.13 |
| Ingenol Mebutate Gel 0.05% | Change From Baseline in Quality of Life (Skindex-29) | Symptoms(Day 29) | 13.89 units on a scale | Standard Deviation 8.83 |
Secondary
Cosmetic Outcomes Assessment (COA)
The investigator rated the subject's Cosmetic Outcomes Assessment(COA) using 5 grades (Very good, Good, No change, Bad, Very bad), and results were as follows.
Time frame: at 29 and 57 days from baseline
Population: Intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 29 | Very bad | 0 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 29 | Very good | 16 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 57 | Good | 39 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 29 | No change | 5 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 57 | No change | 6 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 57 | Very good | 17 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 57 | Bad | 2 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 29 | Bad | 8 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 57 | Very bad | 0 Participants |
| Ingenol Mebutate Gel 0.015% | Cosmetic Outcomes Assessment (COA) | Day 29 | Good | 33 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 57 | Very bad | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 29 | Very good | 3 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 29 | Good | 4 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 29 | No change | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 29 | Bad | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 57 | Very good | 4 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 57 | Good | 5 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 57 | No change | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 57 | Bad | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Cosmetic Outcomes Assessment (COA) | Day 29 | Very bad | 0 Participants |
Secondary
Percentage Change of the Number of AK Lesions in the Selected Treatment Area
Percentage change from baseline in the number of actinic keratiosis(AK) lesions in the selected treatment area on Day 57 was analyzed.
Time frame: Baseline and Day 57
Population: Intent to treat population(Intention To Treat (ITT) set was defined as all subjects who applied the investigational product at least once after the enrollment and allocation during this study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Percentage Change of the Number of AK Lesions in the Selected Treatment Area | -80.08 percentage change | Standard Deviation 38.36 |
| Ingenol Mebutate Gel 0.05% | Percentage Change of the Number of AK Lesions in the Selected Treatment Area | -88.89 percentage change | Standard Deviation 33.33 |
Secondary
Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group
Percentage change from baseline in the number of actinic keratiosis(AK) lesions at Month 6 in the selected treatment area in complete clearance(CC) Group was analyzed.
Time frame: at 6 months from baseline
Population: In intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study), CC Group consisted of 54 participants who had at least 1 follow-up after achieving complete clearance of AK lesions on day 57.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group | -88.65 Percentage change | Standard Deviation 37.61 |
| Ingenol Mebutate Gel 0.05% | Percentage Change of the Number of AK Lesions in the Selected Treatment Area of CC Group | -85.71 Percentage change | Standard Deviation 37.8 |
Secondary
Recurrence Rate in CC Group
Recurrence rate in complete clearance(CC) group was analyzed.
Time frame: at 6 months
Population: In intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study), CC Group consisted of 54 participants who had at least 1 follow-up after achieving complete clearance of AK lesions on Day 57.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Recurrence Rate in CC Group | Recurrence rate | 5 Participants |
| Ingenol Mebutate Gel 0.015% | Recurrence Rate in CC Group | Censored | 42 Participants |
| Ingenol Mebutate Gel 0.05% | Recurrence Rate in CC Group | Recurrence rate | 2 Participants |
| Ingenol Mebutate Gel 0.05% | Recurrence Rate in CC Group | Censored | 5 Participants |
Secondary
Sustained CC Rate in CC Group
Sustained Complete Clearance means that Complete Clearance was maintained until Month 6 in complete clearance (CC) group and sustained complete clearance(CC) rate at month 6 for complete clearance(CC) group was analyzed.
Time frame: at 6 months
Population: In intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study), CC Group consisted of 54 participants who had at least 1 follow-up after achieving complete clearance of AK lesions on Day 57.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Sustained CC Rate in CC Group | Sustained CC | 42 Participants |
| Ingenol Mebutate Gel 0.015% | Sustained CC Rate in CC Group | Recurrence | 5 Participants |
| Ingenol Mebutate Gel 0.05% | Sustained CC Rate in CC Group | Sustained CC | 6 Participants |
| Ingenol Mebutate Gel 0.05% | Sustained CC Rate in CC Group | Recurrence | 1 Participants |
Secondary
Time to Relapse in CC Group
Time to relapse in complete clearance(CC) Group was analyzed. Median survival time with 95% confidence interval was calculated by Kaplan-Meier method.
Time frame: at 6 months
Population: CC Group consisted of 54 participants who had at least 1 follow-up after achieving Complete Clearance of AK lesions on Day 57.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ingenol Mebutate Gel 0.015% | Time to Relapse in CC Group | NA days |
| Ingenol Mebutate Gel 0.05% | Time to Relapse in CC Group | 203 days |
Secondary
Treatment Satisfaction Questionnaire for Medication (TSQM)
Participants personally completed the tool to evaluate satisfaction with drug treatment. It consisted of 4 areas of Effectiveness, side effect, convenience, and global satisfaction, with a total of 14 sub-items. The full mark is 100, and it is divided in four stages as follows. * Very good: 76 -100 score * Good: 51-75 score * Not bad: 26-50 score * Bad: 0-25 score Scores for each area ranged from 0 to 100, with higher scores indicating that fewer side effects had occurred and greater treatment satisfaction.
Time frame: at 29 and 57 days from baseline
Population: Intent to treat population(all participants who applied the investigational product at least once after the enrollment and allocation during this study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Effectiveness(Day 29) | 57.62 units on a scale | Standard Deviation 18.88 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Convenience(Day 29) | 60.75 units on a scale | Standard Deviation 17.38 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Side-effect(Day 29) | 84.48 units on a scale | Standard Deviation 22.4 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Convenience(Day 57) | 65.10 units on a scale | Standard Deviation 15.85 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Effectiveness(Day 57) | 62.67 units on a scale | Standard Deviation 16.22 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Global satisfaction(Day 29) | 59.22 units on a scale | Standard Deviation 18.89 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Side-effect(Day 57) | 89.26 units on a scale | Standard Deviation 19.84 |
| Ingenol Mebutate Gel 0.015% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Global satisfaction(Day 57) | 60.60 units on a scale | Standard Deviation 18.27 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Side-effect(Day 57) | 91.41 units on a scale | Standard Deviation 21.89 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Effectiveness(Day 29) | 61.11 units on a scale | Standard Deviation 11.79 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Effectiveness(Day 57) | 70.37 units on a scale | Standard Deviation 14.7 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Side-effect(Day 29) | 91.67 units on a scale | Standard Deviation 14.99 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Global satisfaction(Day 57) | 63.49 units on a scale | Standard Deviation 21.26 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Convenience(Day 29) | 61.11 units on a scale | Standard Deviation 15.96 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Convenience(Day 57) | 65.43 units on a scale | Standard Deviation 16.62 |
| Ingenol Mebutate Gel 0.05% | Treatment Satisfaction Questionnaire for Medication (TSQM) | Global satisfaction(Day 29) | 65.08 units on a scale | Standard Deviation 14.48 |
Other Pre-specified
Medication for Actinic Keratosis
The count of participants in complete clearance(CC) group and Non-CC group who administered medication for actinic keratosis on the selected treatment area after Day 57 was collected.
Time frame: from 57 days to 6 months
Population: The number of participants who had at least 1 follow-up after assessment of treatment response on Day 57 was 67 and which is consisit of CC group(54 participants) and Non-CC group(13 participants). The CC group and Non-CC group for Ingenol Mebutate Gel 0.015% and 0.05% were intended to be analyzed together.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Medication for Actinic Keratosis | Fluorouracil | 0 Participants |
| Ingenol Mebutate Gel 0.015% | Medication for Actinic Keratosis | Imiquimod | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Medication for Actinic Keratosis | Fluorouracil | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Medication for Actinic Keratosis | Imiquimod | 0 Participants |
Other Pre-specified
Non-Drug Treatment/Surgery for Actinic Keratosis
The count of participants in complete clearance(CC) group and Non-CC group who received non-drug treatment/surgery for actinic keratosis on the selected treatment area after Day 57 was collected.
Time frame: from 57 days to 6 months
Population: The number of participants who had at least 1 follow-up after assessment of treatment response on Day 57 and which is consisit of CC group(54 participants) and Non-CC group(13 participants). The CC group /Non-CC group for Ingenol Mebutate Gel 0.015% and 0.05% were intended to be analyzed together.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Skin cryotherapy | 5 Participants |
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Photodynamic therapy | 0 Participants |
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Phototherapy | 0 Participants |
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Skin lesion excision | 1 Participants |
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Wound treatment | 1 Participants |
| Ingenol Mebutate Gel 0.015% | Non-Drug Treatment/Surgery for Actinic Keratosis | Biopsy skin | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Wound treatment | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Skin cryotherapy | 4 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Skin lesion excision | 0 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Photodynamic therapy | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Biopsy skin | 1 Participants |
| Ingenol Mebutate Gel 0.05% | Non-Drug Treatment/Surgery for Actinic Keratosis | Phototherapy | 1 Participants |