Trial Outcomes & Findings for 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 (NCT NCT01787383)

NCT ID: NCT01787383

Last Updated: 2025-02-24

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

3 days after treatment of each selected treatment area

Results posted on

2025-02-24

Participant Flow

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

Participant milestones

Participant milestones
Measure
Ingenol Mebutate Gel Simultaneous Treatment
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 Sequential Treatment
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.
Overall Study
STARTED
101
98
Overall Study
COMPLETED
92
76
Overall Study
NOT COMPLETED
9
22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 Participants
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 Sequential Treatment
n=98 Participants
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
n=199 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
12 Participants
n=5 Participants
9 Participants
n=7 Participants
21 Participants
n=5 Participants
Age, Categorical
>=65 years
89 Participants
n=5 Participants
89 Participants
n=7 Participants
178 Participants
n=5 Participants
Age, Continuous
74.4 years
n=5 Participants
74.5 years
n=7 Participants
74.5 years
n=5 Participants
Sex: Female, Male
Female
13 Participants
n=5 Participants
18 Participants
n=7 Participants
31 Participants
n=5 Participants
Sex: Female, Male
Male
88 Participants
n=5 Participants
80 Participants
n=7 Participants
168 Participants
n=5 Participants
Region of Enrollment
Italy
63 participants
n=5 Participants
61 participants
n=7 Participants
124 participants
n=5 Participants
Region of Enrollment
Spain
38 participants
n=5 Participants
37 participants
n=7 Participants
75 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 Participants
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 Sequential Treatment
n=98 Participants
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.
Composite Local Skin Reaction (LSR) Score 3 Days After Treatment of Each Selected Treatment Area
10.4 units on a scale
Standard Deviation 5.1
9.7 units on a scale
Standard Deviation 4.5

SECONDARY outcome

Timeframe: 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").

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 Participants
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 Sequential Treatment
n=98 Participants
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.
Complete Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
52.7 percentage of participants
46.9 percentage of participants

SECONDARY outcome

Timeframe: 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").

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 Participants
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 Sequential Treatment
n=98 Participants
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.
Partial Clearance of AKs in Each Separate Treatment Area 8 Weeks After Treatment
76.6 percentage of participants
68.1 percentage of participants

SECONDARY outcome

Timeframe: 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").

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 Participants
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 Sequential Treatment
n=98 Participants
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.
Percent Reduction in Number of AKs in Each Separate Treatment Area 8 Weeks After Treatment
83.4 percentage reduction in number of AKs
Standard Deviation 22.0
79.1 percentage reduction in number of AKs
Standard Deviation 26.7

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=90 Participants
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 Sequential Treatment
n=73 Participants
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.
Effectiveness Satisfaction Questionnaire for Medication (TSQM)
63.1 units on a scale
Standard Deviation 23.4
66.4 units on a scale
Standard Deviation 21.4

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=90 Participants
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 Sequential Treatment
n=73 Participants
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.
Side Effects TSQM
93.1 units on a scale
Standard Deviation 18.4
96.1 units on a scale
Standard Deviation 16.4

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=82 Participants
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 Sequential Treatment
n=72 Participants
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.
Global Satisfaction TSQM
64.6 units on a scale
Standard Deviation 19.0
67.4 units on a scale
Standard Deviation 20.3

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=83 Participants
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 Sequential Treatment
n=73 Participants
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.
Convenience TSQM
73.7 units on a scale
Standard Deviation 14.6
74.7 units on a scale
Standard Deviation 18.1

Adverse Events

Ingenol Mebutate Gel Simultaneous Treatment

Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths

Ingenol Mebutate Gel Sequential Treatment

Serious events: 4 serious events
Other events: 22 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 participants at risk
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 Sequential Treatment
n=98 participants at risk
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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
0.99%
1/101
0.00%
0/98
Skin and subcutaneous tissue disorders
Skin ulcer
0.99%
1/101
0.00%
0/98
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign renal neoplasm
0.99%
1/101
0.00%
0/98
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/101
1.0%
1/98
Gastrointestinal disorders
Haemorrhagic erosive gastritis
0.00%
0/101
1.0%
1/98
Nervous system disorders
Amnesia
0.00%
0/101
1.0%
1/98
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
0.00%
0/101
1.0%
1/98

Other adverse events

Other adverse events
Measure
Ingenol Mebutate Gel Simultaneous Treatment
n=101 participants at risk
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 Sequential Treatment
n=98 participants at risk
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.
General disorders
Application site pruritus
7.9%
8/101
1.0%
1/98
General disorders
Application site pain
5.0%
5/101
1.0%
1/98
General disorders
Feeling cold
0.00%
0/101
1.0%
1/98
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
3.0%
3/101
3.1%
3/98
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
0.99%
1/101
2.0%
2/98
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
0.00%
0/101
1.0%
1/98
Nervous system disorders
Headache
5.0%
5/101
2.0%
2/98
Nervous system disorders
Loss of consciousness
0.00%
0/101
1.0%
1/98
Eye disorders
Conjunctivitis
0.00%
0/101
1.0%
1/98
Eye disorders
Eyelid oedema
0.99%
1/101
0.00%
0/98
Eye disorders
Scotoma
0.99%
1/101
0.00%
0/98
Infections and infestations
Bronchitis
0.99%
1/101
1.0%
1/98
Infections and infestations
Urinary tract infection
0.00%
0/101
1.0%
1/98
Injury, poisoning and procedural complications
Application site burn
0.99%
1/101
1.0%
1/98
Injury, poisoning and procedural complications
Fall
0.00%
0/101
1.0%
1/98
Skin and subcutaneous tissue disorders
Actinic keratosis
0.99%
1/101
0.00%
0/98
Skin and subcutaneous tissue disorders
Rash
0.00%
0/101
1.0%
1/98
Skin and subcutaneous tissue disorders
Subcutaneous nodule
0.99%
1/101
0.00%
0/98
Ear and labyrinth disorders
Vertigo
0.99%
1/101
0.00%
0/98
Psychiatric disorders
Depression
0.00%
0/101
1.0%
1/98
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
0.00%
0/101
1.0%
1/98
Vascular disorders
Hypertension
0.00%
0/101
1.0%
1/98
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/101
1.0%
1/98

Additional Information

Clinical trial disclosure manager

LEO Pharma A/S

Phone: 00 45 44 94 58 88

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60