Actinic Keratosis
Conditions
Keywords
Peplin, PEP005, Actinic Keratosis
Brief summary
This Phase II study is designed to evaluate the pharmacokinetics of PEP005 (ingenol mebutate) Gel, 0.05% when applied in a maximal use setting to the dorsal aspect of the forearm in patients with actinic keratoses
Interventions
PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days
DRUGVehicle Gel
Vehicle Gel once daily for 2 consecutive days
Sponsors
Peplin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female; * Multiple actinic keratosis (AK) lesions over a 100 cm\^2 area of skin located on the dorsal aspect of one forearm.
Exclusion criteria
* Cosmetic or therapeutic procedures: within 2 weeks and within 2 cm of the selected treatment area(s); * Treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system: within 4 weeks; * Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 8 weeks and within 2 cm of the selected treatment area(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | 1 day | Maximum observed concentration (Cmax) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels over the 24 hour sampling time period based on actual values measured. Blood samples were taken: at 30 minutes, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. |
| Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels. | 1 day | Time at which Cmax is attained (Tmax) for ingenol mebutate, and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. If a maximum value occured at more than one timepoint Tmax is defined as the first timepoint with this value. |
| Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | 1 day | Area under the blood conc. versus time curve was calculated for time 0-24 hours (AUC(0-24)) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With Incidence of Pigmentation and Scarring | Baseline, Day 2, 3, 8, 15, 29 and 57 | Patients with Incidence of pigmentation and scarring, and grade of pigmentation and scarring, following study treatment through Day 57 |
| Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area | baseline and day 57 | Number of participants with complete clearence. Complete clearance rate is defined as no clinically visible actinic keratosis (AK) lesions in a 25 cm\^2 area within the selected treatment area at Day 57 compared to baseline |
| Max Composite Local Skin Response (LSR) Score | Day 3 | Max composite Local Skin Response (LSR) score on day 3 only . The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. (One vehicle treated patent had a LSR on day 1 only). |
| Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area | Baseline and Day 57 | Percentage (%) change in actinic keratosis (AK) lesions count at Day 57, compared to baseline, in a 25 cm\^2 area within the selected treatment area. |
| Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study. | baseline and Day 2, 3, 8, 15, 29 and 57 | Number of patients with LSR at any time point during the study above 0. The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. |
Countries
United States
Participant flow
Recruitment details
Study Period: First patient randomized: March 18, 2009 Last patient completed Day 57: May 27, 2009 A single site in the US
Participants by arm
| Arm | Count |
|---|---|
| PEP005 Gel, 0.05% PEP005 (ingenol mebutate) Gel 0.05% once daily for 2 consecutive days | 13 |
| Vehicle Vehicle gel once daily for 2 consecutive days | 3 |
| Total | 16 |
Baseline characteristics
| Characteristic | Vehicle | PEP005 Gel, 0.05% | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 5 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 8 Participants | 10 Participants |
| Age, Continuous | 64.7 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 9.7 | 63.3 years STANDARD_DEVIATION 9.7 |
| Region of Enrollment United States | 3 participants | 13 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 13 | 2 / 3 |
| serious Total, serious adverse events | 0 / 13 | 0 / 3 |
Outcome results
Primary
Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels
Area under the blood conc. versus time curve was calculated for time 0-24 hours (AUC(0-24)) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2.
Time frame: 1 day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PEP005 Gel, 0.05% | Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | NA ng/mL x h |
| Vehicle | Area Under the Blood Conc. Versus Time Curve for Time 0-24 Hours (AUC(0-24)) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | NA ng/mL x h |
Primary
Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels
Maximum observed concentration (Cmax) for ingenol mebutate and its two acyl isomers (PEP015 and PEP025) levels over the 24 hour sampling time period based on actual values measured. Blood samples were taken: at 30 minutes, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2.
Time frame: 1 day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PEP005 Gel, 0.05% | Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | NA ng/mL |
| Vehicle | Maximum Observed Concentration (Cmax) for Ingenol Mebutate and Its Two Acyl Isomers (PEP015 and PEP025) Levels | NA ng/mL |
Primary
Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels.
Time at which Cmax is attained (Tmax) for ingenol mebutate, and its two acyl isomers (PEP015 and PEP025) levels measured at 30 min, 1, 2, 4, 8, 12 and 24 hours following study medication application on Day 2. If a maximum value occured at more than one timepoint Tmax is defined as the first timepoint with this value.
Time frame: 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.05% | Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels. | NA hours |
| Vehicle | Time at Which Cmax is Attained (Tmax) for Ingenol Mebutate, and Its Two Acyl Isomers (PEP015 and PEP025) Levels. | NA hours |
Secondary
Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area
Number of participants with complete clearence. Complete clearance rate is defined as no clinically visible actinic keratosis (AK) lesions in a 25 cm\^2 area within the selected treatment area at Day 57 compared to baseline
Time frame: baseline and day 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.05% | Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area | 10 participants |
| Vehicle | Complete Clearance Rate in a 25 cm^2 Area Within the Selected Treatment Area | 0 participants |
Secondary
Max Composite Local Skin Response (LSR) Score
Max composite Local Skin Response (LSR) score on day 3 only . The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24. (One vehicle treated patent had a LSR on day 1 only).
Time frame: Day 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PEP005 Gel, 0.05% | Max Composite Local Skin Response (LSR) Score | 6.6 local skin response score | Standard Deviation 3.1 |
| Vehicle | Max Composite Local Skin Response (LSR) Score | 0 local skin response score | Standard Deviation 0 |
Secondary
Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study.
Number of patients with LSR at any time point during the study above 0. The treatment area was assessed at baseline and at each subsequent study visit for the presence and grade of the following Local Skin Responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using the Local Skin Response Grading Scale (version 5). Each LSR was graded from 0 (best outcome) to 4 (worst outcome). A composite LSR score was calculated as the sum of each individual LSR grade, giving a possible range of 0-24.
Time frame: baseline and Day 2, 3, 8, 15, 29 and 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.05% | Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study. | 13 participants |
| Vehicle | Number of Patients With Local Skin Responses (LSRs) Above 0 at Any Time Point During the Study. | 1 participants |
Secondary
Patients With Incidence of Pigmentation and Scarring
Patients with Incidence of pigmentation and scarring, and grade of pigmentation and scarring, following study treatment through Day 57
Time frame: Baseline, Day 2, 3, 8, 15, 29 and 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEP005 Gel, 0.05% | Patients With Incidence of Pigmentation and Scarring | 0 participants |
| Vehicle | Patients With Incidence of Pigmentation and Scarring | 0 participants |
Secondary
Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area
Percentage (%) change in actinic keratosis (AK) lesions count at Day 57, compared to baseline, in a 25 cm\^2 area within the selected treatment area.
Time frame: Baseline and Day 57
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PEP005 Gel, 0.05% | Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area | -96 change from baseline lesion count (%) | Standard Deviation 8 |
| Vehicle | Percentage (%) Change in Actinic Keratosis (AK) Lesions in a 25 cm^2 Area Within the Selected Treatment Area | 33 change from baseline lesion count (%) | Standard Deviation 58 |