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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000037-23 | EudraCT Number |
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To identify the Maximum Tolerated Dose levels of LEO 43204 after once daily treatment for two consecutive days and to evaluate efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: LEO 43204 | Other | Open-label, dose escalation, 2 days treatment |
|
| Part 2: LEO 43204 x dose | Active Comparator | X dose for 2 days treatment |
|
| Part 2: LEO 43204 Y dose | Active Comparator | Y dose for 2 days treatment |
|
| Part 2: Placebo | Placebo Comparator | Placebo for 2 days treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LEO 43204 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | The number participants experiencing a DLT was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants experiencing a DLT. A DLT was defined as:
The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. | From Day 1 up to and including Day 8 |
| Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count | Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) in the selected treatment area. | From baseline to Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: Participants With Complete Clearance of AKs | Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in AK count. | From baseline to Week 8 |
| Part 2: Participants With Partial Clearance of AKs |
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Inclusion Criteria:
Exclusion Criteria:
Location of the treatment area
Prior treatment with ingenol mebutate gel on the treatment area
Lesions in the treatment areas that have
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan Weiss, MD | Gwinnett Clinical Research Center, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gwinnett Clinical Research Center, Inc. | Snellville | Georgia | 30078 | United States |
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| Label | URL |
|---|---|
| Clinical Trials at LEO Pharma | View source |
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Participants were recruited in 7 centres in the US into Part 1 of the trial. First participant was enrolled on 14-05-14 and the last subject´s last visit (LSLV) was on 12-08-14. Participants were recruited in 11 centres in the US and 5 centres in Germany into Part 2 of trial. First participant was enrolled on 03-09-14 and LSLV was on 02-03-14.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 - 0.018% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel (ingenol disoxate) 0.018% for two consecutive days on balding scalp. |
| FG001 | Part 1 - 0.025% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.025% for two consecutive days on balding scalp. |
| FG002 | Part 1 - 0.037% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.036% for two consecutive days on balding scalp. |
| FG003 | Part 1 - 0.05% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. |
| FG004 | Part 1 - 0.075% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.075% for two consecutive days on balding scalp. |
| FG005 | Part 2 - Vehicle | Part 2 - Dose finding Once daily application with LEO 43204 gel vehicle for two consecutive days on balding scalp. |
| FG006 | Part 2 - 0.037% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp. |
| FG007 | Part 2 - 0.05% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 - 0.018% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.018% for two consecutive days on balding scalp. |
| BG001 | Part 1 - 0.025% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.025% for two consecutive days on balding scalp. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part 1: Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | The number participants experiencing a DLT was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants experiencing a DLT. A DLT was defined as:
The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. | Posted | Count of Participants | Participants | From Day 1 up to and including Day 8 |
|
Part 1: From Day 1 to Week 2 Part 2: From Day 1 to Week 8
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1 - 0.018% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.018% for two consecutive days on balding scalp. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Brain neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site pruritus | General disorders | MedDRA (15.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Specialist | LEO Pharma A/S | +45 44945888 | disclosure@leo-pharma.com |
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| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C000612882 | LEO 43204 |
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| Drug |
|
Partial clearance of AKs at Week 8 was defined as at least 75% reduction from baseline in AK count.
| From baseline to Week 8 |
| BG002 | Part 1 - 0.037% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp. |
| BG003 | Part 1 - 0.05% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. |
| BG004 | Part 1 - 0.075% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.075% for two consecutive days on balding scalp. |
| BG005 | Part 2 - Vehicle | Part 2 - Dose finding Once daily application with LEO 43204 gel vehicle for two consecutive days on balding scalp. |
| BG006 | Part 2 - 0.037% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp. |
| BG007 | Part 2 - 0.05% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. |
| BG008 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.018% for two consecutive days on balding scalp. |
| OG001 | Part 1 - 0.025% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.025% for two consecutive days on balding scalp. |
| OG002 | Part 1 - 0.037% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.036% for two consecutive days on balding scalp. |
| OG003 | Part 1 - 0.05% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. |
| OG004 | Part 1 - 0.075% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.075% for two consecutive days on balding scalp. |
|
|
| Primary | Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Lesion Count | Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) in the selected treatment area. | Posted | Mean | 95% Confidence Interval | percentage of reduction | From baseline to Week 8 |
|
|
|
|
| Secondary | Part 2: Participants With Complete Clearance of AKs | Complete clearance of AKs at Week 8 was defined as a 100% reduction from baseline in AK count. | Posted | Number | 95% Confidence Interval | percentage of participants | From baseline to Week 8 |
|
|
|
|
| Secondary | Part 2: Participants With Partial Clearance of AKs | Partial clearance of AKs at Week 8 was defined as at least 75% reduction from baseline in AK count. | Posted | Number | 95% Confidence Interval | percentage of participants | From baseline to Week 8 |
|
|
|
|
| 0 |
| 10 |
| 7 |
| 10 |
| EG001 | Part 1 - 0.025% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.025%for two consecutive days on balding scalp. | 0 | 11 | 7 | 11 |
| EG002 | Part 1 - 0.037% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.036% for two consecutive days on balding scalp. | 0 | 12 | 12 | 12 |
| EG003 | Part 1 - 0.05% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. | 0 | 12 | 10 | 12 |
| EG004 | Part 1 - 0.075% Cohort | Part 1 - Dose escalation Once daily application with LEO 43204 gel 0.075% for two consecutive days on balding scalp. | 0 | 12 | 12 | 12 |
| EG005 | Part 2 - Vehicle | Part 2 - Dose finding Once daily application with LEO 43204 gel vehicle for two consecutive days on balding scalp. | 0 | 32 | 4 | 32 |
| EG006 | Part 2 - 0.037% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.037% for two consecutive days on balding scalp. | 2 | 64 | 47 | 64 |
| EG007 | Part 2 - 0.05% | Part 2 - Dose finding Once daily application with LEO 43204 gel 0.05% for two consecutive days on balding scalp. | 3 | 67 | 50 | 67 |
| Atrial flutter | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site paraesthesia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site discomfort | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site discharge | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site hyperaesthesia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Application site oedema | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Accidental exposure | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood urine present | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Circumoral oedema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cholecystectomy | Surgical and medical procedures | MedDRA (15.1) | Non-systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Electrocardiogram abnormal | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Discomfort | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Electrocardiogram t wave abnormal | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Electrocardiogram u-wave abnormality | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Nasal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Onychomycosis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Scar | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Peripheral artery aneurysm | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Visceral larva migrans | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Xerophthalmia | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
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.
| D017437 |
| Skin and Connective Tissue Diseases |
| Negative binomial regression |
| <0.001 |
| Rate ratio |
| 0.25 |
| 2-Sided |
| 95 |
| 0.18 |
| 0.33 |
| Superiority or Other (legacy) |
| Negative binominal regression with log baseline count as offset variable and treatment group and analysis site as factors. | Negative binomial regression | =0.096 | Rate ratio | 0.79 | 2-Sided | 95 | 0.59 | 1.04 | Superiority or Other (legacy) |
| Log binomial regression |
| =0.001 |
| Ratio of clearance rates |
| 8.82 |
| 2-Sided |
| 95 |
| 1.99 |
| 154.5 |
| Superiority or Other (legacy) |
| Log binomial regression with treatment group as factor and baseline AK count included as covariate. | Log binomial regression | =0.43 | Ratio of clearance rates | 1.26 | 2-Sided | 95 | 0.72 | 2.31 | Superiority or Other (legacy) |
| Ratio of clearance rates |
| 9.55 |
| 2-Sided |
| 95 |
| 3.22 |
| 56.4 |
| Superiority or Other (legacy) |
| Log binomial regression | =0.55 | Ratio of clearance rates | 1.09 | 2-Sided | 95 | 0.81 | 1.49 | Superiority or Other (legacy) |