Trial Outcomes & Findings for Ingenol Mebutate Gel, 0.015% Repeat Use for Multiple Actinic Keratoses on Face and Scalp (NCT NCT01600014)

Last Updated: 2025-03-10

Results Overview

The complete clearance rates 8 weeks after randomisation was compared between ingenol mebutate gel, 0.015% and vehicle gel. Complete clearance was defined as no clinically visible AKs in the Selected Treatment Area (STA)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

463 participants

Primary outcome timeframe

8 weeks after randomisation

Results posted on

2025-03-10

Participant Flow

First Subject First Visit: 04-Jun-2012 Last Subject Last Visit: 05-Feb-2014

A total of 463 subjects were enrolled, 13 of whom were screening failures. 450 subjects were allocated to open label treatment with ingenol mebutate gel (1st cycle) and subsequently administered a 2nd cycle in a randomised vehicle controlled setting, if eligible for repeat use

Participant milestones

Participant milestones
Measure	Ingenol Mebutate Gel, 0.015% (1st & 2nd Cycle) Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52	Vehicle Gel (2nd Cycle) Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with vehicle gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52
1. Cycle & Observation Period D1 to W52 STARTED	450	0
1. Cycle & Observation Period D1 to W52 COMPLETED	162	0
1. Cycle & Observation Period D1 to W52 NOT COMPLETED	288	0
2. Cycle Recalcitrant Subgroup W8 to W52 STARTED	92	49
2. Cycle Recalcitrant Subgroup W8 to W52 COMPLETED	80	39
2. Cycle Recalcitrant Subgroup W8 to W52 NOT COMPLETED	12	10
2. Cycl Recurrent Subgroup W26/44 to W52 STARTED	42	20
2. Cycl Recurrent Subgroup W26/44 to W52 COMPLETED	39	20
2. Cycl Recurrent Subgroup W26/44 to W52 NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ingenol Mebutate Gel, 0.015% (1st & 2nd Cycle) Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52	Vehicle Gel (2nd Cycle) Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by observation and/or repeat use (2nd cycle) once daily for 3 consecutive days with vehicle gel of the same treatment area, in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup) with follow-up until Week 52
1. Cycle & Observation Period D1 to W52 Withdrawal by Subject	24	0
1. Cycle & Observation Period D1 to W52 Included in 2nd cycle	203	0
1. Cycle & Observation Period D1 to W52 Adverse Event	6	0
1. Cycle & Observation Period D1 to W52 Other	27	0
1. Cycle & Observation Period D1 to W52 Exclusion Criteria Emerging during Study	14	0
1. Cycle & Observation Period D1 to W52 Protocol Violation	6	0
1. Cycle & Observation Period D1 to W52 Lost to Follow-up	8	0
2. Cycle Recalcitrant Subgroup W8 to W52 Death	1	2
2. Cycle Recalcitrant Subgroup W8 to W52 Other	1	3
2. Cycle Recalcitrant Subgroup W8 to W52 Withdrawal by Subject	2	1
2. Cycle Recalcitrant Subgroup W8 to W52 Lack of Efficacy	1	0
2. Cycle Recalcitrant Subgroup W8 to W52 Protocol Violation	5	0
2. Cycle Recalcitrant Subgroup W8 to W52 Exclusion Criteria Emerging during Study	1	1
2. Cycle Recalcitrant Subgroup W8 to W52 Lost to Follow-up	1	3
2. Cycl Recurrent Subgroup W26/44 to W52 Adverse Event	1	0
2. Cycl Recurrent Subgroup W26/44 to W52 Withdrawal by Subject	1	0
2. Cycl Recurrent Subgroup W26/44 to W52 Lost to Follow-up	1	0

Baseline Characteristics

Ingenol Mebutate Gel, 0.015% Repeat Use for Multiple Actinic Keratoses on Face and Scalp

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ingenol Mebutate 0.015% Gel (1.& 2. Cycle) n=450 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by observation and/or controlled repeat use (2nd cycle) treatment of recalcitrant or recurrent AK lesions
Age, Continuous	71.7 years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants
Sex: Female, Male Male	397 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks after randomisation

Outcome measures

Outcome measures
Measure	Ingenol Mebutate Gel, 0.015% Field Recalcitrant Subgroup n=92 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Vehicle Gel Field Recalcitrant Subgroup n=49 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Ingenol Mebutate Gel 0.015% Field Recurrent Subgroup n=42 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup n=20 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup See primary endpoint for previously defined description
Number of Participants With Complete Clearance of AKs 8 Weeks After Randomisation	43 participants	9 participants	25 participants	5 participants	—

SECONDARY outcome

Timeframe: From last treatment cycle through to Month 12

The analysis was done separately for the field recalcitrant subgroup, the field recurrent subgroup, and overall for all treated subject (Analysis 1, 2, and 3, respectively)

Outcome measures

Outcome measures
Measure	Ingenol Mebutate Gel, 0.015% Field Recalcitrant Subgroup n=247 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Vehicle Gel Field Recalcitrant Subgroup n=92 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Ingenol Mebutate Gel 0.015% Field Recurrent Subgroup n=49 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup n=42 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup n=20 Participants See primary endpoint for previously defined description
Number of Participants With Complete Clearance Through to Month 12, Defined as no Clinically Visible AKs and no Lesions Treated in the Selected Treatment Area at Any Time From Last Treatment Cycle Through to Month 12	124 participants	17 participants	2 participants	13 participants	3 participants

SECONDARY outcome

Timeframe: 8 weeks after randomisation

The change in AK count from randomisation to 8 weeks after randomisation was determined for the field recalcitrant and the field recurrent subgroups

Outcome measures

Outcome measures
Measure	Ingenol Mebutate Gel, 0.015% Field Recalcitrant Subgroup n=92 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Vehicle Gel Field Recalcitrant Subgroup n=49 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 8 with follow-up until Week 52	Ingenol Mebutate Gel 0.015% Field Recurrent Subgroup n=42 Participants Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup n=20 Participants Open label topical field treatment once daily for 3 consecutive days with mebutate 0.015% gel (1st cycle) within a 25 cm\^2 treatment area on the face or scalp, followed by once daily for 3 consecutive days with vehicle gel of the same treatment area (2nd cycle), in a randomised, controlled, double-blind setting, at Week 26 or Week 44 with follow-up until Week 52	Vehicle Gel Field Recurrent Subgroup See primary endpoint for previously defined description
The Change in AK Count From Randomisation to 8 Weeks After Randomisation	-1.41 AK count Standard Deviation 1.49	-0.51 AK count Standard Deviation 1.65	-1.52 AK count Standard Deviation 1.49	-0.85 AK count Standard Deviation 0.99	—

Adverse Events

Ingenol Mebutate 0.015% Gel (1. Cycle)

Serious events: 7 serious events

Other events: 197 other events

Deaths: 0 deaths

Ingenol Mebutate 0.015% Gel (2. Cycle)

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Vehicle Gel (2. Cycle)

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ingenol Mebutate 0.015% Gel (1. Cycle) n=450 participants at risk Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel within a 25 cm2 treatment area on the face or scalp	Ingenol Mebutate 0.015% Gel (2. Cycle) n=134 participants at risk Repeat use once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup)	Vehicle Gel (2. Cycle) n=69 participants at risk Repeat use once daily for 3 consecutive days with vehicle gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.22% 1/450 • Number of events 2 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	1.4% 1/69 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	1.4% 1/69 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Cardiac disorders Myocardial infarction	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Respiratory, thoracic and mediastinal disorders Lung disorder	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Nervous system disorders Cerebrovascular accident	0.22% 1/450 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Reproductive system and breast disorders Prostatism	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	1.4% 1/69 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	0.75% 1/134 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)

Other adverse events

Other adverse events
Measure	Ingenol Mebutate 0.015% Gel (1. Cycle) n=450 participants at risk Open label topical field treatment once daily for 3 consecutive days with ingenol mebutate 0.015% gel within a 25 cm2 treatment area on the face or scalp	Ingenol Mebutate 0.015% Gel (2. Cycle) n=134 participants at risk Repeat use once daily for 3 consecutive days with ingenol mebutate 0.015% gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup)	Vehicle Gel (2. Cycle) n=69 participants at risk Repeat use once daily for 3 consecutive days with vehicle gel of the same treatment area (25 cm2 treatment area on the face or scalp) in a randomised, controlled, double-blind setting, at Week 8 (field recalcitrant subgroup) or Week 26 or Week 44 (field recurrent subgroup)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	4.2% 19/450 • Number of events 23 • 8-week treatment periods (1st or 2nd cycle)	3.7% 5/134 • Number of events 11 • 8-week treatment periods (1st or 2nd cycle)	8.7% 6/69 • Number of events 8 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	2.2% 3/134 • Number of events 3 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	3.0% 4/134 • Number of events 6 • 8-week treatment periods (1st or 2nd cycle)	5.8% 4/69 • Number of events 6 • 8-week treatment periods (1st or 2nd cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	2.2% 3/134 • Number of events 3 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Nervous system disorders Headache	4.7% 21/450 • Number of events 24 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	2.9% 2/69 • Number of events 2 • 8-week treatment periods (1st or 2nd cycle)
Eye disorders Eyelid oedema	3.8% 17/450 • Number of events 18 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
Eye disorders Periorbital oedema	3.3% 15/450 • Number of events 16 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
General disorders Application site pain	13.8% 62/450 • Number of events 71 • 8-week treatment periods (1st or 2nd cycle)	11.2% 15/134 • Number of events 19 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/69 • 8-week treatment periods (1st or 2nd cycle)
General disorders Application site pruritus	4.4% 20/450 • Number of events 20 • 8-week treatment periods (1st or 2nd cycle)	5.2% 7/134 • Number of events 7 • 8-week treatment periods (1st or 2nd cycle)	1.4% 1/69 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)
Skin and subcutaneous tissue disorders Actinic keratosis	9.6% 43/450 • Number of events 51 • 8-week treatment periods (1st or 2nd cycle)	15.7% 21/134 • Number of events 38 • 8-week treatment periods (1st or 2nd cycle)	4.3% 3/69 • Number of events 4 • 8-week treatment periods (1st or 2nd cycle)
Infections and infestations Nasopharyngitis	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	2.2% 3/134 • Number of events 3 • 8-week treatment periods (1st or 2nd cycle)	1.4% 1/69 • Number of events 1 • 8-week treatment periods (1st or 2nd cycle)
Infections and infestations Oral herpes	0.00% 0/450 • 8-week treatment periods (1st or 2nd cycle)	0.00% 0/134 • 8-week treatment periods (1st or 2nd cycle)	2.9% 2/69 • Number of events 2 • 8-week treatment periods (1st or 2nd cycle)

Additional Information

Clinical Trial Disclosure Manager

LEO Pharma A/S

Phone: +45 44945888

Email: [email protected]

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. 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