A Simultaneous Treatment Regimen Compared to a Sequential Treatment Regimen With Ingenol Mebutate Gel 0.015% and 0.05% of Two Areas With Actinic Keratosis on Face/Scalp and Trunk/Extremities

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01787383
• Collaborator: (none)
• Enrollment: 200
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 18.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the safety of a simultaneous treatment regimen compared to a sequential treatment regimen when two separate areas with AKs (one located on face/scalp and the other located on trunk/ extremities) are treated with ingenol mebutate gel

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Drug: Ingenol mebutate gel 0.05 %; Drug: Ingenol mebutate gel 0.015 %	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Simultaneous Treatment Regimen Compared to a Sequential Treatment Regimen With Ingenol Mebutate Gel 0.015% and 0.05% of Two Areas With Actinic Keratosis on Face/Scalp and Trunk/Extremities
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ingenol mebutate gel 0.05 %	Drug: Ingenol mebutate gel 0.05 %; Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities either applied simultaneously or sequentially; Other Names: Picato® ; Drug: Ingenol mebutate gel 0.015 %; Ingenol mebutate gel 0.015 % (Picato®) on face/scalp either applied simultaneously or sequentially; Other Names: Picato®
Active Comparator: Ingenol mebutate gel 0.015 %	Drug: Ingenol mebutate gel 0.05 %; Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities either applied simultaneously or sequentially; Other Names: Picato® ; Drug: Ingenol mebutate gel 0.015 %; Ingenol mebutate gel 0.015 % (Picato®) on face/scalp either applied simultaneously or sequentially; Other Names: Picato®

Outcome Measures

Primary Outcome Measures

1. Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area [3 days after treatment of each selected treatment area]

   Composite Local Skin Reaction (LSR) score 3 days after treatment of each selected treatment area in both treatment groups (simultaneous or sequential). The composite LSR score (0 to 24), reflecting the sum of the individual LSR grades (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, grade 0 to 4), was calculated for each selected treatment area at each visit.The composite LSR score ranges from 0 (best possible outcome) to 24 (worst possible outcome). Both affected areas were calculated together "Per Arm". Each subject could contribute with up to 2 values (1 for each treated area).

Secondary Outcome Measures

1. Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment [8 weeks after treatment]

   Complete clearance of Actinic Keratosis lesions (AKs) analysed in each separate treatment area and presented by treatment regimen given as "percentage of participants" with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").

2. Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment [8 weeks after treatment]

   Partial clearance of Actinic Keratosis lesions (AKs) defined as 75% or greater reduction in Actinic Keratosis lesions (AKs) from start of treatment to 8 weeks after treatment, was analysed in each separate treatment area and presented by treatment regimen given as "percentage of participatns" with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").

3. Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment [8 weeks after treatment]

   Percent reduction in number of Actinic Keratosis lesions (AKs) analysed for each separate treatment area and presented by treatment regimen. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").

4. Effectiveness Satisfaction Questionnaire for Medication (TSQM) [8 weeks]

   Effectiveness TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived effectiveness of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).

5. Side Effects TSQM [8 weeks]

   Side Effects TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived side effects of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).

6. Global Satisfaction TSQM [8 weeks]

   Global Satisfaction TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived overall satisfaction with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).

7. Convenience TSQM [8 weeks]

   Convenience TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived convenience with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must provide informed consent

• Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on face or scalp

• Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm2 treatment area on trunk or extremities

• Subjects at least 18 years of age

• Female subjects must be of either:

1. Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,

2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy.

• Female subjects of childbearing potential must be willing to use effective contraception at trial entry and until completion.

Exclusion Criteria:

• Location of the selected treatment areas:

• on the periorbital skin

• within 5 cm of an incompletely healed wound

• within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)

• Prior treatment with ingenol mebutate gel on face/scalp and on trunk/extremities

• Lesions in the selected treatment areas that have:

• atypical clinical appearance (and/or,

• recalcitrant disease

• History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication

• Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the selected treatment areas

• Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator's clinical judgment.

• Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application.

• Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel

• Presence of sunburn within the selected treatment areas

• Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial

• Subjects previously randomised in the trial

• Female subjects who are breastfeeding

• In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol

Prohibited Therapies and/or Medications within 2 weeks prior to Visit 1:

• Cosmetic or therapeutic procedures within 2 cm of the selected treatment areas

• Use of topical keratolytic therapeutic products within 2 cm of the selected treatment areas

• Use of topical medicated creams, ointments, lotions, gels, foams or sprays including topical steroids : within 2 cm of the selected treatment areas; artificial tanners: within 5 cm of the selected treatment areas

Prohibited Therapies and/or Medications: within 4 weeks prior to Visit 1:

• Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers

• Treatment with systemic medications that suppress the immune system

• Treatment/therapy with ultraviolet light A (UVA) or ultraviolet light B (UVB)

Prohibited Therapies and/or Medications within 8 weeks prior to Visit 1:

• Treatment with 5-fluorouracil (5-FU), imiquimod, topical diclofenac sodium, or photodynamic therapy within 2 cm of the selected treatment areas.

Prohibited Therapies and/or Medications within 6 months prior to Visit 1:

• Use of systemic retinoids or biologic/monoclonal antibody therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinica Dermatologica dell'Università di Modena e Reggio Emilia	Modena		Italy	41124

Sponsors and Collaborators

• LEO Pharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT01787383
• Other Study ID Numbers: LP0041-64; 2012-002863-88
• First Posted: Feb 8, 2013
• Last Update Posted: Jun 22, 2021
• Last Verified: May 1, 2021

• Keywords provided by LEO Pharma: Actinic Keratosis; Ingenol mebutate gel
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis

Study Results

Participant Flow

Pre-assignment Detail	In the clinical study protocol 200 subjects were planned to be enrolled and 199 subjects were actually enrolled and randomised.

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
Period Title: Overall Study
STARTED	101	98
COMPLETED	92	76
NOT COMPLETED	9	22

Baseline Characteristics

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment	Total
Arm/Group Description	Ingenol mebutate gel 0.05 %: Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities applied simultaneously Ingenol mebutate gel 0.015 %: Ingenol mebutate gel 0.015 % (Picato®) on face/scalp applied simultaneously	Ingenol mebutate gel 0.05 %: Ingenol mebutate gel 0.05 % (Picato®) on trunk/extremities applied sequentially Ingenol mebutate gel 0.015 %: Ingenol mebutate gel 0.015 % (Picato®) on face/scalp applied sequentially	Total of all reporting groups
Overall Participants	101	98	199
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 11.9%	9 9.2%	21 10.6%
>=65 years	89 88.1%	89 90.8%	178 89.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	74.4	74.5	74.5
Sex: Female, Male (Count of Participants)
Female	13 12.9%	18 18.4%	31 15.6%
Male	88 87.1%	80 81.6%	168 84.4%
Region of Enrollment (participants) [Number]
Italy	63 62.4%	61 62.2%	124 62.3%
Spain	38 37.6%	37 37.8%	75 37.7%

Outcome Measures

1. Primary Outcome

Title	Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area
Description	Composite Local Skin Reaction (LSR) score 3 days after treatment of each selected treatment area in both treatment groups (simultaneous or sequential). The composite LSR score (0 to 24), reflecting the sum of the individual LSR grades (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, grade 0 to 4), was calculated for each selected treatment area at each visit.The composite LSR score ranges from 0 (best possible outcome) to 24 (worst possible outcome). Both affected areas were calculated together "Per Arm". Each subject could contribute with up to 2 values (1 for each treated area).
Time Frame	3 days after treatment of each selected treatment area

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
Measure Participants	101	98
Mean (Standard Deviation) [units on a scale]	10.4 (5.1)	9.7 (4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Description	Complete clearance of Actinic Keratosis lesions (AKs) analysed in each separate treatment area and presented by treatment regimen given as "percentage of participants" with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").
Time Frame	8 weeks after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
Measure Participants	101	98
Number [percentage of participants]	52.7 52.2%	46.9 47.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Regression, Logistic
	Comments

3. Secondary Outcome

Title	Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Description	Partial clearance of Actinic Keratosis lesions (AKs) defined as 75% or greater reduction in Actinic Keratosis lesions (AKs) from start of treatment to 8 weeks after treatment, was analysed in each separate treatment area and presented by treatment regimen given as "percentage of participatns" with complete AK clearance. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").
Time Frame	8 weeks after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
Measure Participants	101	98
Number [percentage of participants]	76.6 75.8%	68.1 69.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments
	Method	Regression, Logistic
	Comments

4. Secondary Outcome

Title	Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment
Description	Percent reduction in number of Actinic Keratosis lesions (AKs) analysed for each separate treatment area and presented by treatment regimen. Each subject could contribute with up to 2 values (1 for each treated area). Both affected areas were calculated together "Per Arm" (e.g. "averaged").
Time Frame	8 weeks after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
Measure Participants	101	98
Mean (Standard Deviation) [percentage reduction in number of AKs]	83.4 (22.0)	79.1 (26.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Effectiveness Satisfaction Questionnaire for Medication (TSQM)
Description	Effectiveness TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived effectiveness of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Effectiveness TSQM compliance was lower than the number of randomised subjects.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Effectiveness TSQM compliance was lower than the number of randomised subjects.
Measure Participants	90	73
Mean (Standard Deviation) [units on a scale]	63.1 (23.4)	66.4 (21.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Side Effects TSQM
Description	Side Effects TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived side effects of medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Side EffectsTSQM compliance was lower than the number of randomised subjects.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Side Effects TSQM compliance was lower than the number of randomised subjects.
Measure Participants	90	73
Mean (Standard Deviation) [units on a scale]	93.1 (18.4)	96.1 (16.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Global Satisfaction TSQM
Description	Global Satisfaction TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived overall satisfaction with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Global Satisfaction TSQM compliance was lower than the number of randomised subjects.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Global Satisfaction TSQM compliance was lower than the number of randomised subjects.
Measure Participants	82	72
Mean (Standard Deviation) [units on a scale]	64.6 (19.0)	67.4 (20.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Convenience TSQM
Description	Convenience TSQM After a Treatment Cycle of 8 Weeks. Measurement of the perceived convenience with medication, ranging from 0 (worst possible outcome) to 100 (best possible outcome).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment	Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Convenience TSQM compliance was lower than the number of randomised subjects.	Ingenol mebutate gel in 2 doses (0.015 %: and 0.05 %) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities. The Convenience TSQM compliance was lower than the number of randomised subjects.
Measure Participants	83	73
Mean (Standard Deviation) [units on a scale]	73.7 (14.6)	74.7 (18.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ingenol Mebutate Gel Simultaneous Treatment, Ingenol Mebutate Gel Sequential Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Ingenol Mebutate Gel Simultaneous Treatment		Ingenol Mebutate Gel Sequential Treatment
Arm/Group Description	Ingenol mebutate gel in 2 doses (0.015% and 0.05%) were applied simultaneously: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.		Ingenol mebutate gel in 2 doses (0.015% and 0.05%) were applied sequentially: ingenol mebutate gel 0.015% (Picato®) was applied once daily for 3 consecutive days on on face/scalp and ingenol mebutate gel 0.05% (Picato®) was applied once daily for 2 consecutive days on trunk/extremities.
All Cause Mortality
	Ingenol Mebutate Gel Simultaneous Treatment		Ingenol Mebutate Gel Sequential Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ingenol Mebutate Gel Simultaneous Treatment		Ingenol Mebutate Gel Sequential Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/101 (3%)		4/98 (4.1%)
Gastrointestinal disorders
Haemorrhagic erosive gastritis	0/101 (0%)		1/98 (1%)
Metabolism and nutrition disorders
Hyperglycaemia	0/101 (0%)		1/98 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	1/101 (1%)		0/98 (0%)
Benign renal neoplasm	1/101 (1%)		0/98 (0%)
Basal cell carcinoma	0/101 (0%)		1/98 (1%)
Nervous system disorders
Amnesia	0/101 (0%)		1/98 (1%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/101 (1%)		0/98 (0%)
Other (Not Including Serious) Adverse Events
	Ingenol Mebutate Gel Simultaneous Treatment		Ingenol Mebutate Gel Sequential Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/101 (21.8%)		22/98 (22.4%)
Ear and labyrinth disorders
Vertigo	1/101 (1%)		0/98 (0%)
Eye disorders
Conjunctivitis	0/101 (0%)		1/98 (1%)
Eyelid oedema	1/101 (1%)		0/98 (0%)
Scotoma	1/101 (1%)		0/98 (0%)
General disorders
Application site pruritus	8/101 (7.9%)		1/98 (1%)
Application site pain	5/101 (5%)		1/98 (1%)
Feeling cold	0/101 (0%)		1/98 (1%)
Infections and infestations
Bronchitis	1/101 (1%)		1/98 (1%)
Urinary tract infection	0/101 (0%)		1/98 (1%)
Injury, poisoning and procedural complications
Application site burn	1/101 (1%)		1/98 (1%)
Fall	0/101 (0%)		1/98 (1%)
Metabolism and nutrition disorders
Hyperglycaemia	0/101 (0%)		1/98 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	3/101 (3%)		3/98 (3.1%)
Squamous cell carcinoma of skin	1/101 (1%)		2/98 (2%)
Malignant melanoma	0/101 (0%)		1/98 (1%)
Nervous system disorders
Headache	5/101 (5%)		2/98 (2%)
Loss of consciousness	0/101 (0%)		1/98 (1%)
Psychiatric disorders
Depression	0/101 (0%)		1/98 (1%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/101 (0%)		1/98 (1%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/101 (1%)		0/98 (0%)
Rash	0/101 (0%)		1/98 (1%)
Subcutaneous nodule	1/101 (1%)		0/98 (0%)
Vascular disorders
Hypertension	0/101 (0%)		1/98 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.