Trial Outcomes & Findings for PEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Reflectance Confocal Microscopy (NCT NCT01449513)

NCT ID: NCT01449513

Last Updated: 2025-03-07

Results Overview

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 24 participants
• Primary outcome timeframe: Baseline to Day 3
• Results posted on: 2025-03-07

Participant Flow

Start date: 27-Sep-2011 (FSFV - first subject first visit) Completion date: 22-May-2012 (LSLV - last subject last visit)

Participant milestones

Measure	Ingenol Mebutate Gel (PEP005 Gel) Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Overall Study STARTED	16	8
Overall Study COMPLETED	16	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Reflectance Confocal Microscopy

Baseline characteristics by cohort

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle n=8 Participants Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Age, Continuous	70.8 years STANDARD_DEVIATION 7.5 • n=5 Participants	69.9 years STANDARD_DEVIATION 3.5 • n=7 Participants	70.5 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Germany	16 participants n=5 Participants	8 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by Reflectance Confocal Microscopy (RCM) in actinic keratosis (AK) skin.This RCM imaging technique is a relatively new non-invasive, real-time evaluation method to generate horizontal skin sections at a resolution comparable to routine histology.

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	1.42 percentage change Standard Deviation 0.94	—

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by Reflectance Confocal Microscopy (RCM) in Sub actinic keratosis (AK) skin.

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	1.52 percentage of change Standard Deviation 0.74	—

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin.

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	0.94 percentage of change Standard Deviation 0.68	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	2.24 percentage of change Standard Deviation 0.77	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin.

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	2.07 percentage of change Standard Deviation 0.76	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	1.38 percentage of change Standard Deviation 0.50	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	0.90 percentage of change Standard Deviation 0.90	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	1.16 percentage of change Standard Deviation 0.95	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	0.31 percentage of change Standard Deviation 0.60	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	-0.60 percentage of change Standard Deviation 0.62	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	0.03 percentage of change Standard Deviation 0.47	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of infiltration will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of infiltration of the epidermis by inflammatory cells following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

The degree of infiltration of the epidermis by inflammatory cells will be based on "inflammation/small bright cells" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel. The degree of infiltration of the dermis by inflammatory cells will be based on "inflammatory cells in the dermis" (grading 0-3) as assessed by RCM from baseline across the trial period for the subjects receiving PEP005 Gel.

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Infiltration	0 percentage of change Standard Deviation 0	—

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	1.69 percentage of change Standard Deviation 0.93	—

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	1.42 percentage of change Standard Deviation 0.90	—

PRIMARY outcome

Timeframe: Baseline to Day 2

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0.81 percentage of change Standard Deviation 0.66	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM(Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	2.44 percentage of change Standard Deviation 0.69	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	2.16 percentage of change Standard Deviation 0.86	—

PRIMARY outcome

Timeframe: Baseline to Day 3

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	1.38 percentage of change Standard Deviation 0.72	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0.31 percentage of change Standard Deviation 0.66	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0.28 percentage of change Standard Deviation 0.68	—

PRIMARY outcome

Timeframe: Baseline to Day 8

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel,0.05% as assessed by RCM (Reflectance Confocal Microscopy) in normal skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0 percentage of change Standard Deviation 0	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0 percentage of change Standard Deviation 0	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM (Reflectance Confocal Microscopy) in Sub AK (actinic keratosis) skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0 percentage of change Standard Deviation 0	—

PRIMARY outcome

Timeframe: Baseline to Day 57

Population: As stated in the outcome measure, the degree of necrosis will be assessed for subjects receiving Ingenol Mebutate Gel. Therefor this is 0 for all subjects receiving vehicle.

Change from baseline in the degree of necrosis in the epidermis following treatment with ingenol mebutate gel, 0.05% as assessed by RCM in normal skin

Outcome measures

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 Participants Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Change in Degree of Necrosis	0 percentage of change Standard Deviation 0	—

Adverse Events

Ingenol Mebutate Gel (PEP005 Gel)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 participants at risk Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle n=8 participants at risk Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Vascular disorders Hypertensive crisis	6.2% 1/16 • Number of events 1	0.00% 0/8

Other adverse events

Measure	Ingenol Mebutate Gel (PEP005 Gel) n=16 participants at risk Ingenol mebutate gel (PEP005 gel) Ingenol mebutate gel (0.05%) once daily on two consecutive days to an 25cm2 area	Vehicle n=8 participants at risk Vehicle of PEP005 Gel Vehicle gel once daily on two consecutive days to an 25cm2 area
Cardiac disorders Angina pectoris	6.2% 1/16	0.00% 0/8
Cardiac disorders Arteriosclerosis coronary artery	6.2% 1/16	0.00% 0/8
General disorders Hyperthermia	6.2% 1/16	0.00% 0/8
General disorders Pain	62.5% 10/16	0.00% 0/8
General disorders Swelling	6.2% 1/16	0.00% 0/8
Infections and infestations Postoperative wound	6.2% 1/16	0.00% 0/8
Metabolism and nutrition disorders Hypercholesterolaemia	6.2% 1/16	0.00% 0/8
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/16	12.5% 1/8
Nervous system disorders Burning sensation	18.8% 3/16	0.00% 0/8
Nervous system disorders Paraesthesia	6.2% 1/16	0.00% 0/8
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 1/16	0.00% 0/8
Skin and subcutaneous tissue disorders Pain of skin	12.5% 2/16	0.00% 0/8
Skin and subcutaneous tissue disorders Pruritus	31.2% 5/16	0.00% 0/8
Skin and subcutaneous tissue disorders Skin burning sensation	50.0% 8/16	0.00% 0/8
Skin and subcutaneous tissue disorders Skin oedema	6.2% 1/16	0.00% 0/8
Vascular disorders Hypertension	6.2% 1/16	0.00% 0/8
Vascular disorders Hypertensive crisis	6.2% 1/16	0.00% 0/8

Additional Information

Clinical Trial Disclosure Manager

LEO Pharma A/S

Phone: +45 4494 5888

Email: ctr.disclosure@leo-pharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee LEO acknowledges the investigators right to publish the entire results of the study, irrespective of outcome. LEO retains the right to have any publication submitted to LEO for review at least 30 days prior to the same paper being submitted for publication or presentation. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.
• Publication restrictions are in place

Restriction type: OTHER