Trial Outcomes & Findings for Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis (NCT NCT01820260)

NCT ID: NCT01820260

Last Updated: 2025-03-13

Results Overview

Dose tolerability was measures looking at the composite score of Local Skin Responses (LSR). The MTD was defined as the highest dose level with less than 4 subjects out of 12 experiencing dose limiting toxicity (DLT). DLT was defined as one or more of the following three local skin LSRs: * Crusting Grade 4 * Erosion/Ulceration Grade 4 * Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs: * Erythema Grade 4 * Crusting Grade 3 * Swelling Grade 4 * Erosion/Ulceration Grade 3 * Vesiculation/Pustulation Grade 3 The grading is a scale of 1 to 4 (highest grade).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 395 participants
• Primary outcome timeframe: 8 days after initial treatment
• Results posted on: 2025-03-13

Participant Flow

Part 1: There was 1 of the 82 subjects who withdrew before receiving any treatment but after collection of baseline characteristics. 81 subjects received treatment and all completed the trial. Part 2: There were 2 of the 315 randomized subjects who withdrew consent prior to any baseline characteristics being recorded (therefore they received no treatment) and are excluded from the total number of participants, full analysis set and safety analysis.

Participant milestones

Measure	Part 1A: Ingenol Mebutate Gel 0.005% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.018% for 2 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.018% for 3 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 2 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 3 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Vehicle Gel (Placebo) for 2 Days Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Vehicle Gel (Placebo) for 3 Days Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days
Phase 1 (Part 1) STARTED	3	12	10	12	12	10	12	11	0	0	0	0	0	0
Phase 1 (Part 1) COMPLETED	3	12	10	12	12	10	11	11	0	0	0	0	0	0
Phase 1 (Part 1) NOT COMPLETED	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Phase 2 (Part 2) STARTED	0	0	0	0	0	0	0	0	64	62	61	64	31	31
Phase 2 (Part 2) COMPLETED	0	0	0	0	0	0	0	0	64	61	61	64	31	31
Phase 2 (Part 2) NOT COMPLETED	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Reasons for withdrawal

Measure	Part 1A: Ingenol Mebutate Gel 0.005% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.018% for 2 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.018% for 3 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 2 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 3 Days Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Vehicle Gel (Placebo) for 2 Days Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Vehicle Gel (Placebo) for 3 Days Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days
Phase 1 (Part 1) Subject withdrew after randomization before treatment assignment	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Phase 2 (Part 2) Withdrawal by Subject	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis

Baseline characteristics by cohort

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=3 Participants Administration on full face, once daily for 3 days	Part 1A: Ingenol Mebutate Gel 0.008% n=12 Participants Administration on full face, once daily for 3 days	Part 1A: Ingenol Mebutate Gel 0.012% n=10 Participants Administration on full face, once daily for 3 days	Part 1A: Ingenol Mebutate Gel 0.018% n=12 Participants Administration on full face, once daily for 3 days	Part 1A: Ingenol Mebutate Gel 0.027% n=12 Participants Administration on full face, once daily for 3 days	Part 1A: Ingenol Mebutate Gel 0.04% n=10 Participants Administration on full face, once daily for 3 days	Part 1B: Ingenol Mebutate Gel 0.04% n=11 Participants Administration on full face, once daily for 2 days	Part 1B: Ingenol Mebutate Gel 0.06% n=12 Participants Administration on full face, once daily for 2 days	Part 2: Ingenol Mebutate Gel 0.018% for 3 Days Treatment n=62 Participants Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days Ingenol mebutate gel 0.018%	Part 2: Ingenol Mebutate Gel 0.027% for 3 Days Treatment n=64 Participants Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days Ingenol mebutate gel 0.027%	Part 2: Ingenol Mebutate Gel 0.018% for 2 Days Treatment n=64 Participants Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days Ingenol mebutate gel 0.018%	Part 2: Ingenol Mebutate Gel 0.027% for 2 Days Treatment n=61 Participants Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days Ingenol mebutate gel 0.027%	Part 2: Vehicle Gel (Placebo)for 2 Days Treatment n=31 Participants Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days Vehicle gel (placebo)	Part 2: Vehicle Gel (Placebo) for 3 Days Treatment n=31 Participants Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days Vehicle gel (placebo)	Total n=395 Participants Total of all reporting groups
Age, Continuous	75.3 years n=5 Participants	69.6 years n=7 Participants	68.7 years n=5 Participants	67.4 years n=4 Participants	69.7 years n=21 Participants	68.0 years n=8 Participants	67.5 years n=8 Participants	71.7 years n=24 Participants	68.0 years n=42 Participants	66.3 years n=42 Participants	66.9 years n=42 Participants	66.1 years n=42 Participants	68.4 years n=36 Participants	69.0 years n=36 Participants	68.0 years n=24 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	5 Participants n=24 Participants	20 Participants n=42 Participants	15 Participants n=42 Participants	8 Participants n=42 Participants	15 Participants n=42 Participants	3 Participants n=36 Participants	5 Participants n=36 Participants	79 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	11 Participants n=21 Participants	8 Participants n=8 Participants	10 Participants n=8 Participants	7 Participants n=24 Participants	42 Participants n=42 Participants	49 Participants n=42 Participants	56 Participants n=42 Participants	46 Participants n=42 Participants	28 Participants n=36 Participants	26 Participants n=36 Participants	316 Participants n=24 Participants
Region of Enrollment United States	3 participants n=5 Participants	12 participants n=7 Participants	10 participants n=5 Participants	12 participants n=4 Participants	12 participants n=21 Participants	10 participants n=8 Participants	11 participants n=8 Participants	12 participants n=24 Participants	62 participants n=42 Participants	64 participants n=42 Participants	64 participants n=42 Participants	61 participants n=42 Participants	31 participants n=36 Participants	31 participants n=36 Participants	395 participants n=24 Participants

PRIMARY outcome

Timeframe: 8 days after initial treatment

Population: The composite (sum) score was obtained by summing the 6 individual LSRs

Dose tolerability was measures looking at the composite score of Local Skin Responses (LSR). The MTD was defined as the highest dose level with less than 4 subjects out of 12 experiencing dose limiting toxicity (DLT).

DLT was defined as one or more of the following three local skin LSRs:

• Crusting Grade 4
• Erosion/Ulceration Grade 4
• Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs:
• Erythema Grade 4
• Crusting Grade 3
• Swelling Grade 4
• Erosion/Ulceration Grade 3
• Vesiculation/Pustulation Grade 3

The grading is a scale of 1 to 4 (highest grade).

Outcome measures

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=3 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% n=12 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% n=10 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% n=12 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% n=12 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% n=10 Participants Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% n=11 Participants Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% n=11 Participants Administration on full face, once daily for 2 consecutive days
Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	4 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 8 weeks

Number of subjects with complete clearance of Actinic Keratosis lesions (AKs) at week 8 after 2 or 3 consecutive days of treatment with ingenol mebutate gel on the full face, full balding scalp or approximately 250 cm² on the chest

Outcome measures

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=62 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% n=64 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% n=64 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% n=61 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% Administration on full face, once daily for 2 consecutive days
Part 2: Number of Subjects With Complete Clearance of AKs	15 participants	19 participants	25 participants	13 participants	1 participants	0 participants	—	—

SECONDARY outcome

Timeframe: From baseline to Week 8

Reduction in actinic keratosis lesion count from baseline to week 8 (percentage, adjusted for anatomical location and pooled site)

Outcome measures

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=62 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% n=64 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% n=64 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% n=61 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% Administration on full face, once daily for 2 consecutive days
Part 2: Reduction in AK Count	73.5 Percentage reduction Interval 66.4 to 79.1	70.5 Percentage reduction Interval 62.8 to 76.6	82.9 Percentage reduction Interval 77.6 to 86.9	67.7 Percentage reduction Interval 59.1 to 74.5	4.3 Percentage reduction Interval -28.1 to 28.5	15.7 Percentage reduction Interval -12.9 to 37.1	—	—

SECONDARY outcome

Timeframe: Week 8

Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in the number of clinically visible AKs

Outcome measures

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=62 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.008% n=64 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.012% n=62 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.018% n=61 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.027% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1A: Ingenol Mebutate Gel 0.04% n=31 Participants Administration on full face, once daily for 3 consecutive days	Part 1B: Ingenol Mebutate Gel 0.04% Administration on full face, once daily for 2 consecutive days	Part 1B: Ingenol Mebutate Gel 0.06% Administration on full face, once daily for 2 consecutive days
Part 2: Number of Subjects With Partial Clearance of AKs	54.8 percentage of participants	57.8 percentage of participants	76.6 percentage of participants	52.5 percentage of participants	6.5 percentage of participants	12.9 percentage of participants	—	—

Adverse Events

Part 1A: Ingenol Mebutate Gel 0.005%

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1A: Ingenol Mebutate Gel 0.008%

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 1A: Ingenol Mebutate Gel 0.012%

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Part 1A: Ingenol Mebutate Gel 0.018%

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part 1A: Ingenol Mebutate Gel 0.027%

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part 1A: Ingenol Mebutate Gel 0.04%

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part 1B: Ingenol Mebutate Gel 0.04%

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Part 1B: Ingenol Mebutate Gel 0.06%

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part 2: Ingenol Mebutate Gel 0.018% for 3 Days

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Part 2: Ingenol Mebutate Gel 0.018% for 2 Days

Serious events: 0 serious events

Other events: 59 other events

Deaths: 0 deaths

Part 2: Ingenol Mebutate Gel 0.027% for 3 Days

Serious events: 0 serious events

Other events: 60 other events

Deaths: 0 deaths

Part 2: Ingenol Mebutate Gel 0.027% for 2 Days

Serious events: 0 serious events

Other events: 58 other events

Deaths: 0 deaths

Part 2: Vehicle Gel (Placebo) for 3 Days

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 2: Vehicle Gel (Placebo) for 2 Days

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part 1A: Ingenol Mebutate Gel 0.005% n=3 participants at risk Administration on full face, once daily 3 days	Part 1A: Ingenol Mebutate Gel 0.008% n=12 participants at risk Administration on full face, once daily 3 days	Part 1A: Ingenol Mebutate Gel 0.012% n=10 participants at risk Administration on full face, once daily 3 days	Part 1A: Ingenol Mebutate Gel 0.018% n=12 participants at risk Administration on full face, once daily 3 days	Part 1A: Ingenol Mebutate Gel 0.027% n=12 participants at risk Administration on full face, once daily 3 days	Part 1A: Ingenol Mebutate Gel 0.04% n=10 participants at risk Administration on full face, once daily 3 days	Part 1B: Ingenol Mebutate Gel 0.04% n=11 participants at risk Administration on full face, once daily 2 days	Part 1B: Ingenol Mebutate Gel 0.06% n=11 participants at risk Administration on full face, once daily 3 days	Part 2: Ingenol Mebutate Gel 0.018% for 3 Days n=62 participants at risk Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Ingenol Mebutate Gel 0.018% for 2 Days n=64 participants at risk Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 3 Days n=64 participants at risk Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Ingenol Mebutate Gel 0.027% for 2 Days n=61 participants at risk Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days	Part 2: Vehicle Gel (Placebo) for 3 Days n=31 participants at risk Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days	Part 2: Vehicle Gel (Placebo) for 2 Days n=31 participants at risk Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days
General disorders Application site pain	0.00% 0/3	41.7% 5/12	80.0% 8/10	66.7% 8/12	100.0% 12/12	90.0% 9/10	100.0% 11/11	81.8% 9/11	90.3% 56/62	87.5% 56/64	93.8% 60/64	93.4% 57/61	6.5% 2/31	12.9% 4/31
General disorders Application site pruritus	0.00% 0/3	0.00% 0/12	40.0% 4/10	16.7% 2/12	8.3% 1/12	20.0% 2/10	54.5% 6/11	18.2% 2/11	29.0% 18/62	15.6% 10/64	14.1% 9/64	14.8% 9/61	0.00% 0/31	0.00% 0/31
General disorders Application site discomfort	0.00% 0/3	0.00% 0/12	0.00% 0/10	8.3% 1/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	4.7% 3/64	3.1% 2/64	4.9% 3/61	0.00% 0/31	0.00% 0/31
General disorders Application site paraesthesia	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	9.1% 1/11	9.1% 1/11	3.2% 2/62	1.6% 1/64	4.7% 3/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Influenza like illness	0.00% 0/3	0.00% 0/12	0.00% 0/10	8.3% 1/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	3.1% 2/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	3.2% 1/31
General disorders Appilcation site dryness	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	4.8% 3/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
General disorders Cyst rupture	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	3.2% 1/31
Infections and infestations Nasopharyngititis	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	1.6% 1/62	4.7% 3/64	1.6% 1/64	3.3% 2/61	0.00% 0/31	3.2% 1/31
Infections and infestations Sinusitis	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	1.6% 1/64	1.6% 1/64	0.00% 0/61	0.00% 0/31	3.2% 1/31
Infections and infestations Upper respiratory tract infection	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	1.6% 1/64	1.6% 1/61	3.2% 1/31	0.00% 0/31
Infections and infestations Folliculitis	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	1.6% 1/62	0.00% 0/64	0.00% 0/64	1.6% 1/61	3.2% 1/31	0.00% 0/31
Infections and infestations Influenza	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Infections and infestations Herpes zoster	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
Eye disorders Eye irritation	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	8.3% 1/12	10.0% 1/10	9.1% 1/11	9.1% 1/11	3.2% 2/62	3.1% 2/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Eye disorders Eye swelling	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	1.6% 1/62	1.6% 1/64	3.1% 2/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Eye disorders Lacrimation increased	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	1.6% 1/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Nervous system disorders Headache	0.00% 0/3	0.00% 0/12	0.00% 0/10	8.3% 1/12	0.00% 0/12	10.0% 1/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	3.1% 2/64	1.6% 1/64	4.9% 3/61	0.00% 0/31	0.00% 0/31
Investigations Electrocardiogram QT prolonged	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	3.2% 2/62	0.00% 0/64	1.6% 1/64	1.6% 1/61	3.2% 1/31	0.00% 0/31
Psychiatric disorders Insomnia	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	9.1% 1/11	1.6% 1/62	0.00% 0/64	3.1% 2/64	1.6% 1/61	0.00% 0/31	0.00% 0/31
Vascular disorders Hypertension	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	9.1% 1/11	0.00% 0/62	3.1% 2/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Injury, poisoning and procedural complications Procedural pain	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	3.2% 1/31	0.00% 0/31
Eye disorders Eyelid oedema	33.3% 1/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Fatigue	0.00% 0/3	8.3% 1/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	9.1% 1/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Chills	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	10.0% 1/10	9.1% 1/11	0.00% 0/11	1.6% 1/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Nervous system disorders Transient ischaemic attack	0.00% 0/3	8.3% 1/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Application site reaction	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	8.3% 1/12	0.00% 0/10	9.1% 1/11	27.3% 3/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Application site oedema	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	9.1% 1/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Tenderness	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	9.1% 1/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Periorbital oedema	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	9.1% 1/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Skin and subcutaneous tissue disorders Skin burning sensation	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	8.3% 1/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
General disorders Pyrexia	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	10.0% 1/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Eye disorders Conjunctival hyperaemia	0.00% 0/3	0.00% 0/12	0.00% 0/10	8.3% 1/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Infections and infestations oral herpes	0.00% 0/3	0.00% 0/12	20.0% 2/10	8.3% 1/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Infections and infestations Lung infection	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Nervous system disorders Parosmia	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	10.0% 1/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Gastrointestinal disorders Nausea	0.00% 0/3	0.00% 0/12	10.0% 1/10	8.3% 1/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	1.6% 1/64	1.6% 1/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	1.6% 1/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/3	0.00% 0/12	10.0% 1/10	0.00% 0/12	0.00% 0/12	0.00% 0/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Respiratory, thoracic and mediastinal disorders upper airway cough syndrome	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	10.0% 1/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31
Ear and labyrinth disorders Ear pain	0.00% 0/3	0.00% 0/12	0.00% 0/10	0.00% 0/12	0.00% 0/12	10.0% 1/10	0.00% 0/11	0.00% 0/11	0.00% 0/62	0.00% 0/64	0.00% 0/64	0.00% 0/61	0.00% 0/31	0.00% 0/31

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
• Publication restrictions are in place