Skin and Connective Tissue Diseases
Conditions
Keywords
Psoriasis
Brief summary
The purpose of this study is to evaluate the anti-psoriatic effect of LEO 90100 aerosol foam compared with Betesil® medicated plaster
Detailed description
The products will be applied on 6 test sites (each product on 3 test sites) once daily 6 days a week (except Sundays) for 4 weeks. The application sites for each product will be determined according to random assignment. Depending on the size of the psoriasis plaques, 2 or 4 test sites will be located within the same plaque; the treatment assignment will be done pair-wise.
Interventions
DRUGBetesil® 2.25 mg
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent has been obtained * Subjects with a diagnosis of psoriasis vulgaris with preferably three lesions (plaques) located on arms, legs and/or trunk or at least two lesions (plaques) located on arms, legs and/or trunk. For subjects with three lesions, each lesion must have a size suitable to accommodate 2 test sites (test site area 5 cm2, distance between two test sites at least 2 cm). For subjects with two lesions, one lesion must have a size suitable to accommodate 4 test sites, and the other lesion must accommodate 2 test sites. * Age 18 years or above * Outpatients * 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 has tubal ligation) or, * child-bearing potential provided there is a confirmed negative pregnancy test prior to trial treatment to rule out pregnancy.
Exclusion criteria
* Female subjects who are breast feeding * Systemic treatment with biological therapies, whether marketed or not, with a possible effect on psoriasis vulgaris within the following time periods prior to randomisation: * Etanercept - within 4 weeks prior to randomisation and during the trial * Adalimumab, infliximab - within 8 weeks prior to randomisation and during the trial * Ustekinumab - within 16 weeks prior to randomisation and during the trial * Other products - within 4 weeks/5 half-lives prior to randomisation and during the trial (whichever is longer) * Systemic treatment with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within the 4-week period prior to randomisation and during the trial * Subjects using phototherapy within the following time periods prior to randomisation and during the trial: * PUVA: 4 weeks * UVB: 2 weeks * Subjects using one of the following topical drugs for the treatment of psoriasis within the 4 week period prior to randomisation and during the trial: * Potent or very potent (WHO group III-IV) corticosteroids * Subjects using one of the following topical drugs for the treatment of psoriasis within 2 weeks prior to randomisation and during the trial: * WHO group I-II corticosteroids (except if used for treatment of scalp and/or facial psoriasis) * Topical retinoids, Vitamin D analogues, Topical immunomodulators (e.g. calcineurin inhibitors), Tar products, Salicylic acid * Subjects using emollients on the selected plaques within 1 week before randomisation and during the trial * Initiation of, or expected changes to concomitant medication that may affect psoriasis vulgaris (e.g., beta blockers, antimalarial drugs, lithium and ACE inhibitors) within 2 weeks prior to the randomisation and during the trial * Subjects with current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline | Day 1 (Baseline) to Day 29 | The investigator assessed the severity of the clinical signs erythema, scaling, and infiltration for each test site by using a 7-point scale with half-mark values from 0 (no evidence) to 3.0 (severe). The total TCS was calculated for each test site by summing the scores for erythema, scaling, and infiltration for that particular test site. Each test site was assessed at Baseline and on Days 4, 8, 11, 15, 18, 22, 25, and 29 (EoT). The mean TCS at Baseline was 6.6 for both groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TCS at Individual Visits | Day 1 (Baseline) to Day 29 | — |
| Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Day 1 (Baseline) to Day 29 | The investigator assessed the severity of the clinical signs erythema, scaling, and infiltration for each test site by using a 7-point scale with half-mark values from 0 (no evidence) to 3.0 (severe). Erythema: 0 (no evidence - normal skin color) to 3 (severe - intense red). Scaling: 0 (no evidence - no scaling) to 3 (severe - coarse, thick scales). Infiltration: 0 (no evidence - no infiltration) to 3 (severe - very marked infiltration). |
| Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT | Baseline to End of Treatment | Skin thickness ultrasound measurements of the test sites were performed at Baseline and End of Treatment. Two skin parameters were calculated using ultrasound: * The mean total skin thickness * The mean echo-poor band thickness |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Calcipotriol (as monohydrate) 50 mcg/g and betamethasone (as dipropionate) 0.5 mg/g (LEO 90100 Aerosol foam)
LEO 90100 Aerosol foam
Betamethasone (as valerate). Each 7.5 cm x 10 cm medicated plaster contains: 2.250 mg of betamethasone valerate (corresponding to 1.845 mg of betamethasone)
Betesil® 2.25 mg | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Region of Enrollment France | 35 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline
The investigator assessed the severity of the clinical signs erythema, scaling, and infiltration for each test site by using a 7-point scale with half-mark values from 0 (no evidence) to 3.0 (severe). The total TCS was calculated for each test site by summing the scores for erythema, scaling, and infiltration for that particular test site. Each test site was assessed at Baseline and on Days 4, 8, 11, 15, 18, 22, 25, and 29 (EoT). The mean TCS at Baseline was 6.6 for both groups.
Time frame: Day 1 (Baseline) to Day 29
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 90100 Aerosol Foam | Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline | TCS at Baseline | 6.6 units on a scale | Standard Deviation 0.6 |
| LEO 90100 Aerosol Foam | Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline | Change in TCS Baseline to EoT | -5.8 units on a scale | Standard Deviation 1.1 |
| Betesil® 2.25 mg | Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline | TCS at Baseline | 6.6 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, Infiltration) Absolute Change in Total Clinical Score (TCS) of Clinical Signs (Sum of Erythema, Scaling, and Infiltration) at End of Treatment Compared to Baseline | Change in TCS Baseline to EoT | -3.6 units on a scale | Standard Deviation 1.5 |
Comparison: A last observation carried forward (LOCF) approach was used to account for drop-outs and missing values in the analysis of end of treatment values.p-value: <0.00195% CI: [-2.58, -1.76]ANOVA
Secondary
Change in Score of Erythema, Scaling, and Infiltration at Individual Visits
The investigator assessed the severity of the clinical signs erythema, scaling, and infiltration for each test site by using a 7-point scale with half-mark values from 0 (no evidence) to 3.0 (severe). Erythema: 0 (no evidence - normal skin color) to 3 (severe - intense red). Scaling: 0 (no evidence - no scaling) to 3 (severe - coarse, thick scales). Infiltration: 0 (no evidence - no infiltration) to 3 (severe - very marked infiltration).
Time frame: Day 1 (Baseline) to Day 29
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 25/Visit 23 | -1.8 units on a scale | Standard Deviation 0.6 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 4/Visit 5 | -0.5 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 8/Visit 8 | -0.9 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 11/Visit 11 | -1.3 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 15/Visit 14 | -1.4 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 18/Visit 17 | -1.6 units on a scale | Standard Deviation 0.6 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 22/Visit 20 | -1.7 units on a scale | Standard Deviation 0.6 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 29/Visit 26 | -1.9 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 4/Visit 5 | -0.6 units on a scale | Standard Deviation 0.3 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 8/Visit 8 | -1.3 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 11/Visit 11 | -1.7 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 15/Visit 14 | -1.8 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 18/Visit 17 | -1.9 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 22/Visit 20 | -2.0 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 25/Visit 23 | -2.0 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 29/Visit 26 | -2.0 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 4/Visit 5 | -0.3 units on a scale | Standard Deviation 0.2 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 8/Visit 8 | -0.9 units on a scale | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 11/Visit 11 | -1.3 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 15/Visit 14 | -1.6 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 18/Visit 17 | -1.7 units on a scale | Standard Deviation 0.4 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 22/Visit 20 | -1.8 units on a scale | Standard Deviation 0.3 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 25/Visit 23 | -1.9 units on a scale | Standard Deviation 0.3 |
| LEO 90100 Aerosol Foam | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 29/Visit 26 | -1.9 units on a scale | Standard Deviation 0.3 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 25/Visit 23 | -1.0 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 18/Visit 17 | -1.2 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 11/Visit 11 | -0.6 units on a scale | Standard Deviation 0.5 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 8/Visit 8 | -0.6 units on a scale | Standard Deviation 0.4 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 22/Visit 20 | -1.2 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 11/Visit 11 | -0.8 units on a scale | Standard Deviation 0.5 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 22/Visit 20 | -0.9 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 15/Visit 14 | -0.9 units on a scale | Standard Deviation 0.5 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 25/Visit 23 | -1.4 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 18/Visit 17 | -1.0 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 15/Visit 14 | -0.8 units on a scale | Standard Deviation 0.5 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 22/Visit 20 | -1.1 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 4/Visit 5 | -0.4 units on a scale | Standard Deviation 0.4 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 25/Visit 23 | -1.3 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 29/Visit 26 | -1.3 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Erythema Day 29/Visit 26 | -1.2 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 29/Visit 26 | -1.1 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 4/Visit 5 | -0.6 units on a scale | Standard Deviation 0.3 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 4/Visit 5 | -0.3 units on a scale | Standard Deviation 0.2 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 8/Visit 8 | -0.8 units on a scale | Standard Deviation 0.5 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 18/Visit 17 | -0.8 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 11/Visit 11 | -1.0 units on a scale | Standard Deviation 0.6 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Infiltration Day 8/Visit 8 | -0.5 units on a scale | Standard Deviation 0.4 |
| Betesil® 2.25 mg | Change in Score of Erythema, Scaling, and Infiltration at Individual Visits | Scaling Day 15/Visit 14 | -1.1 units on a scale | Standard Deviation 0.6 |
Secondary
Change in TCS at Individual Visits
Time frame: Day 1 (Baseline) to Day 29
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 15/Visit 15 | -4.8 units on a scale | Standard Deviation 1.2 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 8/Visit 8 | -3.2 units on a scale | Standard Deviation 1.2 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 18/Visit 18 | -5.1 units on a scale | Standard Deviation 1.2 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 4/Visit 5 | -1.3 units on a scale | Standard Deviation 0.8 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 25/Visit 23 | -5.7 units on a scale | Standard Deviation 1.1 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 11/Visit 11 | -4.3 units on a scale | Standard Deviation 1.1 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 29/Visit 26 | -5.9 units on a scale | Standard Deviation 1.1 |
| LEO 90100 Aerosol Foam | Change in TCS at Individual Visits | Day 22/Visit 20 | -5.5 units on a scale | Standard Deviation 1.2 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 29/Visit 26 | -3.7 units on a scale | Standard Deviation 1.6 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 4/Visit 5 | -1.3 units on a scale | Standard Deviation 0.7 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 8/Visit 8 | -2.0 units on a scale | Standard Deviation 1.1 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 11/Visit 11 | -2.4 units on a scale | Standard Deviation 1.4 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 15/Visit 15 | -2.8 units on a scale | Standard Deviation 1.4 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 22/Visit 20 | -3.2 units on a scale | Standard Deviation 1.6 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 25/Visit 23 | -3.6 units on a scale | Standard Deviation 1.6 |
| Betesil® 2.25 mg | Change in TCS at Individual Visits | Day 18/Visit 18 | -3.1 units on a scale | Standard Deviation 1.5 |
Secondary
Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT
Skin thickness ultrasound measurements of the test sites were performed at Baseline and End of Treatment. Two skin parameters were calculated using ultrasound: * The mean total skin thickness * The mean echo-poor band thickness
Time frame: Baseline to End of Treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 90100 Aerosol Foam | Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT | Change in Echo-Poor Band Thickness | -1.3 millimeters | Standard Deviation 0.5 |
| LEO 90100 Aerosol Foam | Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT | Change in Total Skin Thickness | -1.0 millimeters | Standard Deviation 0.3 |
| Betesil® 2.25 mg | Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT | Change in Total Skin Thickness | -0.6 millimeters | Standard Deviation 0.4 |
| Betesil® 2.25 mg | Change in Total Skin Thickness and Echo-poor Band Thickness From Baseline to EoT | Change in Echo-Poor Band Thickness | -0.7 millimeters | Standard Deviation 0.5 |
Comparison: Total Skin Thickness: LEO 90100 vs. Betesil®p-value: <0.00195% CI: [-0.53, -0.32]ANOVA
Comparison: Echo-Poor Band Thickness: LEO 90100 vs. Betesil®p-value: <0.00195% CI: [-0.69, -0.41]ANOVA