Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis
Sponsor
LEO Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT01820260
Collaborator
(none)
395
1
14
16
24.7
Study Details
Study Description
Brief Summary
To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
395 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Part 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel groupPart 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel group
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Masking only for Part 2
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy of Escalating Doses of Ingenol Mebutate Once Daily for Two or Three Consecutive Days When Used on Full Face, Full Balding Scalp or Approximately 250 cm2 on the Chest in Subjects With Actinic Keratosis
Study Start Date
:
Apr 1, 2013
Actual Primary Completion Date
:
Aug 1, 2014
Actual Study Completion Date
:
Aug 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1A: Ingenol mebutate gel 0.005% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Active Comparator: Part 2: Ingenol mebutate gel 0.018% for 3 days treatment Randomized, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Active Comparator: Part 2: Ingenol mebutate gel 0.018% for 2 days treatment Randomized 2 days treatment |
Drug: Ingenol mebutate gel
|
| Active Comparator: Part 2: Ingenol mebutate gel 0.027% for 3 days treatment Randomized 3 days treatment |
Drug: Ingenol mebutate gel
|
| Active Comparator: Part 2: Ingenol mebutate gel 0.027% for 2 days treatment Randomized 2 days treatment |
Drug: Ingenol mebutate gel
|
| Placebo Comparator: Part 2: Placebo for 3 days treatment Randomized 3 days treatment |
Drug: placebo
|
| Placebo Comparator: Part 2: Placebo for 2 days treatment Randomized 2 days treatment |
Drug: placebo
|
| Experimental: Part 1A: Ingenol mebutate gel 0.008% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1A: Ingenol mebutate gel 0.012% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1A: Ingenol mebutate gel 0.027% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1A: Ingenol mebutate gel 0.04% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1B: Ingenol mebutate gel 0.06% Open-label, dose escalation, 2 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1A: Ingenol mebutate gel 0.018% Open-label, dose escalation, 3 days treatment |
Drug: Ingenol mebutate gel
|
| Experimental: Part 1B: Ingenol mebutate gel 0.04% Open-label, dose escalation, 2 days treatment |
Drug: Ingenol mebutate gel
|
Outcome Measures
Primary Outcome Measures
- Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days [8 days after initial treatment]
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).
- Part 2: Number of Subjects With Complete Clearance of AKs [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
Secondary Outcome Measures
- Part 2: Reduction in AK Count [From baseline to Week 8]
Reduction in actinic keratosis lesion count from baseline to week 8 (percentage, adjusted for anatomical location and pooled site)
- Part 2: Number of Subjects With Partial Clearance of AKs [Week 8]
Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in the number of clinically visible AKs
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects must be competent to understand the nature of the trial and provide informed consent
-
Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
-
Subject at least 18 years of age
-
Female subjects must be of either:
-
Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
-
Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy
- Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion
Exclusion Criteria:
-
Location of the treatment area (full face, full balding scalp or chest)
-
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 within the treatment area
-
Lesions in the treatment areas that have:
-
atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or,
-
recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions
-
History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
-
Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the 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
-
Any abnormal laboratory tests that are medically significant and would impact the safety of the subjects or the interpretation of the trial results, as determined by the investigator's judgment
-
Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications
-
Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
-
Presence of acute sunburn within the treatment areas
-
Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
-
Subjects previously assigned to treatment in Part 1 or rand
-
Female subjects who are breastfeeding.
-
In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Laser & Skin Surgery Center of Inidana | Carmel | Indiana | United States | 46032 |
Sponsors and Collaborators
- LEO Pharma
Investigators
- Principal Investigator: C. William Hanke, MD, Laser & Skin Surgery Center of Indiana
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
LEO Pharma
ClinicalTrials.gov Identifier:
NCT01820260
Other Study ID Numbers:
- LP0105-1012
First Posted:
Mar 28, 2013
Last Update Posted:
May 25, 2021
Last Verified:
May 1, 2021
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days | Part 2: Vehicle Gel (Placebo) for 2 Days | Part 2: Vehicle Gel (Placebo) for 3 Days |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 2 consecutive days | Administration on full face, once daily for 2 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days | Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days |
| Period Title: Phase 1 (Part 1) | ||||||||||||||
| STARTED | 3 | 12 | 10 | 12 | 12 | 10 | 12 | 11 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 3 | 12 | 10 | 12 | 12 | 10 | 11 | 11 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Phase 1 (Part 1) | ||||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 64 | 62 | 61 | 64 | 31 | 31 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 64 | 61 | 61 | 64 | 31 | 31 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days Treatment | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days Treatment | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days Treatment | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days Treatment | Part 2: Vehicle Gel (Placebo)for 2 Days Treatment | Part 2: Vehicle Gel (Placebo) for 3 Days Treatment | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administration on full face, once daily for 3 days | Administration on full face, once daily for 3 days | Administration on full face, once daily for 3 days | Administration on full face, once daily for 3 days | Administration on full face, once daily for 3 days | Administration on full face, once daily for 3 days | Administration on full face, once daily for 2 days | Administration on full face, once daily for 2 days | 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% | 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% | 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% | 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% | 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) | 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 of all reporting groups |
| Overall Participants | 3 | 12 | 10 | 12 | 12 | 10 | 11 | 12 | 62 | 64 | 64 | 61 | 31 | 31 | 395 |
| Age (years) [Mean (Full Range) ] | |||||||||||||||
| Mean (Full Range) [years] |
75.3
|
69.6
|
68.7
|
67.4
|
69.7
|
68.0
|
67.5
|
71.7
|
68.0
|
66.3
|
66.9
|
66.1
|
68.4
|
69.0
|
68.0
|
| Sex: Female, Male (Count of Participants) | |||||||||||||||
| Female |
0
0%
|
1
8.3%
|
1
10%
|
2
16.7%
|
1
8.3%
|
2
20%
|
1
9.1%
|
5
41.7%
|
20
32.3%
|
15
23.4%
|
8
12.5%
|
15
24.6%
|
3
9.7%
|
5
16.1%
|
79
20%
|
| Male |
3
100%
|
11
91.7%
|
9
90%
|
10
83.3%
|
11
91.7%
|
8
80%
|
10
90.9%
|
7
58.3%
|
42
67.7%
|
49
76.6%
|
56
87.5%
|
46
75.4%
|
28
90.3%
|
26
83.9%
|
316
80%
|
| Region of Enrollment (participants) [Number] | |||||||||||||||
| United States |
3
100%
|
12
100%
|
10
100%
|
12
100%
|
12
100%
|
10
100%
|
11
100%
|
12
100%
|
62
100%
|
64
100%
|
64
100%
|
61
100%
|
31
100%
|
31
100%
|
395
100%
|
Outcome Measures
| Title | Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days |
|---|---|
| Description | 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). |
| Time Frame | 8 days after initial treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The composite (sum) score was obtained by summing the 6 individual LSRs |
| Arm/Group Title | Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 3 consecutive days | Administration on full face, once daily for 2 consecutive days | Administration on full face, once daily for 2 consecutive days |
| Measure Participants | 3 | 12 | 10 | 12 | 12 | 10 | 11 | 11 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
8.3%
|
4
40%
|
1
9.1%
|
0
0%
|
| Title | Part 2: Number of Subjects With Complete Clearance of AKs |
|---|---|
| Description | 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 |
| Time Frame | 8 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ingenol Mebutate Gel 0.018% for 3 Days | Ingenol Mebutate Gel 0.018% for 2 Days | Ingenol Mebutate Gel 0.027% for 3 Days | Ingenol Mebutate Gel 0.027% for 2 Days | Vehicle Gel (Placebo) for 3 Days | Vehicle Gel (Placebo) for 2 Days |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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% | 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% | 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% | 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% | 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) | 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 |
| Measure Participants | 62 | 64 | 64 | 61 | 31 | 31 |
| Number [participants] |
15
500%
|
19
158.3%
|
25
250%
|
13
108.3%
|
1
8.3%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.008%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | Complete clearance of AKs at Week 8 was to be analysed by log binomial regression with factors treatment group, anatomical location (face/chest or scalp) and analysis site. Due to the low numbers of subjects obtaining complete clearance in the vehicle groups,the proposed model did not converge and Fisher's exact test was used instead to compare active treatments with the respective vehicle arm. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | To account for multiple testing, the 4 pairwise tests with corresponding vehicle group were performed using Bonferroni method testing at a 1.25% significance level, securing that the overall significance level did not exceed 5% | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.018%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | See comment in analysis 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0037 |
| Comments | see comments in analysis 1 | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.005%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | See comments in analysis 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0171 |
| Comments | See comments in analysis 1 | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.012%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Part 2: Reduction in AK Count |
|---|---|
| Description | Reduction in actinic keratosis lesion count from baseline to week 8 (percentage, adjusted for anatomical location and pooled site) |
| Time Frame | From baseline to Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ingenol Mebutate Gel 0.018% for 3 Days Treatment | Ingenol Mebutate Gel 0.018% for 2 Days Treatment | Ingenol Mebutate Gel 0.027% for 3 Days Treatment | Ingenol Mebutate Gel 0.027% for 2 Days Treatment | Vehicle Gel (Placebo) for 3 Days Treatment | Vehicle Gel (Placebo)for 2 Days Treatment |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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% | 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% | 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% | 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% | 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) | 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) |
| Measure Participants | 62 | 64 | 64 | 61 | 31 | 31 |
| Number (95% Confidence Interval) [Percentage reduction] |
73.5
|
70.5
|
82.9
|
67.7
|
4.3
|
15.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.005%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | To account for multiple testing among the secondary endpoints, a hierarchical order of testing was determined, where the following evaluation was done separately for each of the four active groups: Provided the primary endpoint was significant at a 1.25% level, the comparison to vehicle in terms of reduction in AK count from baseline to week 8 was tested at a 1.25% level. Provided this test was significant, the second secondary endpoint,partial clearance, was tested(vs. vehicle) at a 1.25% level | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | z-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.008%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | See comment in analysis 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | z-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.012%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | See comment analysis 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | z-test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.018%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | See comment in analysis 1 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | z-test | |
| Comments | ||
| Title | Part 2: Number of Subjects With Partial Clearance of AKs |
|---|---|
| Description | Partial clearance of AKs at Week 8, defined as at least 75% reduction from baseline in the number of clinically visible AKs |
| Time Frame | Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Ingenol Mebutate Gel 0.018% for 3 Days Treatment | Ingenol Mebutate Gel 0.018% for 2 Days Treatment | Ingenol Mebutate Gel 0.027% for 3 Days Treatment | Ingenol Mebutate Gel 0.027% for 2 Days Treatment | Vehicle Gel (Placebo) for 3 Days Treatment | Vehicle Gel (Placebo)for 2 Days Treatment |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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% | 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% | 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% | 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% | 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) | 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) |
| Measure Participants | 62 | 64 | 62 | 61 | 31 | 31 |
| Number [percentage of participants] |
54.8
1826.7%
|
57.8
481.7%
|
76.6
766%
|
52.5
437.5%
|
6.5
54.2%
|
12.9
129%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.005%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | Analysis of partial clearance of AK's at Week 8 was done in the same way as for the primary outcome (endpoint) | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.008%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.012%, Part 1A: Ingenol Mebutate Gel 0.027% |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Part 1A: Ingenol Mebutate Gel 0.018%, Part 1A: Ingenol Mebutate Gel 0.04% |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||
| Arm/Group Title | Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days | Part 2: Vehicle Gel (Placebo) for 3 Days | Part 2: Vehicle Gel (Placebo) for 2 Days | ||||||||||||||
| Arm/Group Description | Administration on full face, once daily 3 days | Administration on full face, once daily 3 days | Administration on full face, once daily 3 days | Administration on full face, once daily 3 days | Administration on full face, once daily 3 days | Administration on full face, once daily 3 days | Administration on full face, once daily 2 days | Administration on full face, once daily 3 days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days | Administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 3 consecutive days | Vehicle gel administration on full face, full balding scalp, or approximately 250 cm² on the chest, once daily for 2 consecutive days | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days | Part 2: Vehicle Gel (Placebo) for 3 Days | Part 2: Vehicle Gel (Placebo) for 2 Days | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days | Part 2: Vehicle Gel (Placebo) for 3 Days | Part 2: Vehicle Gel (Placebo) for 2 Days | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| Part 1A: Ingenol Mebutate Gel 0.005% | Part 1A: Ingenol Mebutate Gel 0.008% | Part 1A: Ingenol Mebutate Gel 0.012% | Part 1A: Ingenol Mebutate Gel 0.018% | Part 1A: Ingenol Mebutate Gel 0.027% | Part 1A: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.04% | Part 1B: Ingenol Mebutate Gel 0.06% | Part 2: Ingenol Mebutate Gel 0.018% for 3 Days | Part 2: Ingenol Mebutate Gel 0.018% for 2 Days | Part 2: Ingenol Mebutate Gel 0.027% for 3 Days | Part 2: Ingenol Mebutate Gel 0.027% for 2 Days | Part 2: Vehicle Gel (Placebo) for 3 Days | Part 2: Vehicle Gel (Placebo) for 2 Days | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 7/12 (58.3%) | 9/10 (90%) | 10/12 (83.3%) | 12/12 (100%) | 10/10 (100%) | 11/11 (100%) | 10/11 (90.9%) | 58/62 (93.5%) | 59/64 (92.2%) | 60/64 (93.8%) | 58/61 (95.1%) | 8/31 (25.8%) | 8/31 (25.8%) | ||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Ear pain | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||
| Eye irritation | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/10 (10%) | 1/11 (9.1%) | 1/11 (9.1%) | 2/62 (3.2%) | 2/64 (3.1%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Eye swelling | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 1/62 (1.6%) | 0 | 1/64 (1.6%) | 0 | 2/64 (3.1%) | 0 | 0/61 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 |
| Lacrimation increased | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 1/64 (1.6%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Eyelid oedema | 1/3 (33.3%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Conjunctival hyperaemia | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Nausea | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Application site pain | 0/3 (0%) | 5/12 (41.7%) | 8/10 (80%) | 8/12 (66.7%) | 12/12 (100%) | 9/10 (90%) | 11/11 (100%) | 9/11 (81.8%) | 56/62 (90.3%) | 56/64 (87.5%) | 60/64 (93.8%) | 57/61 (93.4%) | 2/31 (6.5%) | 4/31 (12.9%) | ||||||||||||||
| Application site pruritus | 0/3 (0%) | 0/12 (0%) | 4/10 (40%) | 2/12 (16.7%) | 1/12 (8.3%) | 2/10 (20%) | 6/11 (54.5%) | 2/11 (18.2%) | 18/62 (29%) | 10/64 (15.6%) | 9/64 (14.1%) | 9/61 (14.8%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Application site discomfort | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 3/64 (4.7%) | 2/64 (3.1%) | 3/61 (4.9%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Application site paraesthesia | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 1/11 (9.1%) | 1/11 (9.1%) | 2/62 (3.2%) | 1/64 (1.6%) | 3/64 (4.7%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Influenza like illness | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 2/64 (3.1%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 1/31 (3.2%) | ||||||||||||||
| Appilcation site dryness | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 3/62 (4.8%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Cyst rupture | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 1/31 (3.2%) | ||||||||||||||
| Fatigue | 0/3 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 1/11 (9.1%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Chills | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | 1/11 (9.1%) | 0/11 (0%) | 1/62 (1.6%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Application site reaction | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | 1/11 (9.1%) | 3/11 (27.3%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Application site oedema | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 1/11 (9.1%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Tenderness | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 1/11 (9.1%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Periorbital oedema | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 1/11 (9.1%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Pyrexia | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Nasopharyngititis | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 1/62 (1.6%) | 3/64 (4.7%) | 1/64 (1.6%) | 2/61 (3.3%) | 0/31 (0%) | 1/31 (3.2%) | ||||||||||||||
| Sinusitis | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | 0/61 (0%) | 0/31 (0%) | 1/31 (3.2%) | ||||||||||||||
| Upper respiratory tract infection | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 1/64 (1.6%) | 1/61 (1.6%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Folliculitis | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 1/62 (1.6%) | 0/64 (0%) | 0/64 (0%) | 1/61 (1.6%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Influenza | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Herpes zoster | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| oral herpes | 0/3 (0%) | 0/12 (0%) | 2/10 (20%) | 1/12 (8.3%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Lung infection | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Procedural pain | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 0/64 (0%) | 1/64 (1.6%) | 1/61 (1.6%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Joint stiffness | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Back pain | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 1/64 (1.6%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Scoliosis | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Salivary gland neoplasm | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Headache | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 1/12 (8.3%) | 0/12 (0%) | 1/10 (10%) | 0/11 (0%) | 0/11 (0%) | 2/62 (3.2%) | 2/64 (3.1%) | 1/64 (1.6%) | 3/61 (4.9%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Transient ischaemic attack | 0/3 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Parosmia | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Insomnia | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 1/11 (9.1%) | 1/62 (1.6%) | 0/64 (0%) | 2/64 (3.1%) | 1/61 (1.6%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Pulmonary congestion | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Nasal septum deviation | 0/3 (0%) | 0/12 (0%) | 1/10 (10%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| upper airway cough syndrome | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 1/10 (10%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Pruritus | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 1/31 (3.2%) | 0/31 (0%) | ||||||||||||||
| Skin burning sensation | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 1/12 (8.3%) | 0/10 (0%) | 0/11 (0%) | 0/11 (0%) | 0/62 (0%) | 0/64 (0%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||
| Hypertension | 0/3 (0%) | 0/12 (0%) | 0/10 (0%) | 0/12 (0%) | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 1/11 (9.1%) | 0/62 (0%) | 2/64 (3.1%) | 0/64 (0%) | 0/61 (0%) | 0/31 (0%) | 0/31 (0%) | ||||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure Manager |
|---|---|
| Organization | LEO Pharma A/S |
| Phone | +45 4494 5888 |
| ctr.disclosure@leo-pharma.com |
Responsible Party:
LEO Pharma
ClinicalTrials.gov Identifier:
NCT01820260
Other Study ID Numbers:
- LP0105-1012
First Posted:
Mar 28, 2013
Last Update Posted:
May 25, 2021
Last Verified:
May 1, 2021