The Pharmacokinetics of LEO 90105 (Calcipotriol Hydrate Plus Betamethasone Dipropionate) in Japanese Subjects With Extensive Psoriasis Vulgaris

Study Overview
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Brief Summary
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The pharmacokinetics of LEO 90105 (calcipotriol hydrate plus betamethasone dipropionate) in Japanese subjects with extensive psoriasis vulgaris.

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: LEO 90105


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese subjects having understood and signed a written informed consent form prior to any study related procedures being carried out (including activities related to the wash out period) 20 years of age or above. Either sex. Clinical diagnosis of psoriasis vulgaris amenable to topical treatment involving arms and/or trunk and/or legs. Psoriasis vulgaris on the trunk/limbs (excluding psoriasis on the genitals/skin folds) of not more than 30% body surface area (BSA) An Investigator's global assessment of disease severity (IGA) on area(s) to be treated of moderate, severe or very severe and a m-PASI score of ≥12. Females of childbearing potential must have a negative result for a urine pregnancy test at Day 1 (Visit 1) and must agree to use an adequate method of birth control, as judged by the (sub)investigator, during the study. The contraceptive method should have started an adequate amount of time before the pregnancy test, which is dependent on the particular method used and as judged by the (sub)investigator, and must continue for at least 1 week after the last application of study medication. A female is defined as not of child-bearing potential if she is postmenopausal (12 months with no menses without an alter-native medical cause) or surgically sterile (tubal ligation /section, hysterectomy or bilateral ovariectomy). Exclusion Criteria: Systemic use of biological treatments with a potential effect on psoriasis vulgaris within the following time periods prior to Visit 1: etanercept, adalimumab, infliximab -3 months. ustekinumab - 4 months other products - within 3 months/5 half-lives (whichever is longer). Systemic treatments with all therapies other than biological treatments with a potential effect on psoriasis vulgaris (e.g., corticosteroids, vitamin D analogues, retinoids, immu-nosuppressants such as ciclosporin and methotrexate) within 4 weeks prior to Visit 1 (use of inhaled and nasal corticosteroids is allowed, use of systemic antihistamines is allowed). Topical treatment of scalp psoriasis with vitamin D analogues (e.g. calcipotriol, tacalcitol, maxacalcitol), or very potent WHO group IV corticosteroids within 2 weeks prior to Visit 1. PUVA therapy, UVB therapy or UVA therapy within 4 weeks prior to Visit 1. Topical treatment of psoriasis on the face, genitals or skin folds with vitamin D analogues (e.g. calcipotriol, tacalcitol, maxacalcitol), or potent or very potent WHO group III or IV corticosteroids within 2 weeks prior to Visit 1. Topical treatment of psoriasis on area(s) to be treated with study medication within the 2-week period prior to Visit 1. (Use of emollients is allowed during this 2- week period, but not during the study.) Planned initiation of, or changes in, concomitant medication that may affect psoriasis vulgaris (e.g., beta-blockers, antimalaria drugs, lithium and ACE inhibitors) during the study. Topical treatment of conditions other than psoriasis with vitamin D analogues (e.g. calcipotriol, tacalcitol, maxacalcitol), or potent or very potent WHO group III or IV corti-costeroids within 2 weeks prior to Visit 1. Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis. Clinical signs or symptoms of Cushing's disease or Addison's disease Patients with any of the following disorders (a) or symptoms (b) present on the area(s) to be treated with study medication: (a) viral (e.g., herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, acne vulgaris, atrophic skin, striae atrophicae, ichthyosis, acne rosacea, ulcers, burns, frostbite, wounds, or (b) fragility of skin veins. Other inflammatory skin diseases (e.g., seborrhoeic dermatitis, contact dermatitis and cutaneous mycosis) that may confound the evaluation of psoriasis vulgaris. Planned excessive exposure of treated areas(s) to either natural or artificial sunlight (including tanning boths, sun lamps, etc) during the study. Known or suspected disorders of calcium metabolism associated with hypercalcaemia (subjects with results for albumin-corrected serum calcium above the reference range from the sample taken at the Washout/Screening Visit. Severe renal insufficiency, severe hepatic disorders or severe heart disease. Known or suspected hypersensitivity to components of the investigational products. Current participation in any other interventional clinical study Subjects who have received treatment with any non-marketed drug substance (i.e. an agent which has not yet been made available for clinical use following registration) within the 4-week period prior to Visit 1 or longer, if the class of substance re-quires a longer washout as defined above (e.g. biological treatments). Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding Patients suspected of being unable to comply with the study protocol, e.g. due to alcoholism, drug dependence or psychotic state. Previous enrollment in this study. Hospitalised patients.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 90105 Ointment<br> | Drug: LEO 90105<br>* Once daily for four weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic: Cmax of Betamethasone Dipropionate | The mean Cmax(Maximum Observed Plasma Concentration) of betamethasone dipropionate was determined. | Day 1 | 
| Pharmacokinetic: Cmax of Betamethasone Dipropionate | The mean Cmax (Maximum Observed Plasma Concentration) of betamethasone dipropionate was determined | Day 7 | 
| Pharmacokinetic: Cmax of Betamethasone Dipropionate | The mean Cmax (Maximum Observed Plasma Concentration) of betamethasone dipropionate was determined | Day 14 | 
| Pharmacokinetic: AUClast of Betamethasone Dipropionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone dipropionate was determined | Day 1 | 
| Pharmacokinetic: AUClast of Betamethasone Dipropionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone dipropionate was determined | Day 7 | 
| Pharmacokinetic: AUClast of Betamethasone Dipropionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone dipropionate was determined | Day 14 | 
| Pharmacokinetic: Cmax of Betamethasone 17-propionate | The mean Cmax(Maximum Observed Plasma Concentration) of betamethasone 17- propionate was determined | Day 1 | 
| Pharmacokinetic: Cmax of Betamethasone 17-propionate | The mean Cmax (Maximum Observed Plasma Concentration) of betamethasone 17- propionate was determined | Day 7 | 
| Pharmacokinetic: Cmax of Betamethasone 17-propionate | The mean Cmax (Maximum Observed Plasma Concentration) of betamethasone 17- propionate was determined | Day 14 | 
| Pharmacokinetic: AUClast of Betamethasone 17-propionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone 17-propionate was determined | Day 1 | 
| Pharmacokinetic: AUClast of Betamethasone 17-propionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone 17-propionate was determined | Day 7 | 
| Pharmacokinetic: AUClast of Betamethasone 17-propionate | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for betamethasone 17-propionate was determined | Day 14 | 
| Pharmacokinetic: Cmax of Calcipotriol | The mean Cmax (Maximum Observed Plasma Concentration) of calcipotriol was determined | Day 1 | 
| Pharmacokinetic: Cmax of Calcipotriol | The mean Cmax (Maximum Observed Plasma Concentration) of calcipotriol was determined | Day 7 | 
| Pharmacokinetic: Cmax of Calcipotriol | The mean Cmax (Maximum Observed Plasma Concentration) of calcipotriol was determined | Day 14 | 
| Pharmacokinetic: AUClast of Calcipotriol | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for calcipotriol was determined | Day 1 | 
| Pharmacokinetic: AUClast of Calcipotriol | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for calcipotriol was determined | Day 7 | 
| Pharmacokinetic: AUClast of Calcipotriol | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for calcipotriol was determined | Day 14 | 
| Pharmacokinetic: Cmax of MC1080 | The mean Cmax (Maximum Observed Plasma Concentration) of MC1080 was determined | Day 1 | 
| Pharmacokinetic: Cmax of MC1080 | The mean Cmax (Maximum Observed Plasma Concentration) of MC1080 was determined | Day 7 | 
| Pharmacokinetic: Cmax of MC1080 | The mean Cmax (Maximum Observed Plasma Concentration) of MC1080 was determined | Day 14 | 
| Pharmacokinetic: AUClast of MC1080 | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for MC 1080 was determined | Day 1 | 
| Pharmacokinetic: AUClast of MC1080. | To assess the The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for MC 1080 was determined | Day 7 | 
| Pharmacokinetic: AUClast of MC1080. | The mean AUClast (Area under the Plasma Concentration-Time Curve from Time 0 to the Last Observed Measurable Concentration) for MC 1080 was determined | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Percentage Change in m-PASI From Baseline to Day 28 | Psoriasis Area and Severity Index (PASI) is based on the investigator's assessment of the disease. The extent and severity of redness, thickness and scaliness of psoriasis are recorded for three regions (arms, trunk and legs) and these are used to calculate PASI. The PASI can range between 0 (best) to 64.8 (worst). m-PASI indicate that the scale is modified. | Baseline to Day 28 | 
| Efficacy: Subjects With 'Clear' or 'Almost Clear' Disease by Investigator's Global Assessment at Day 28. | Subjects with 'clear' or 'almost clear' disease by investigator's globala ssessment at day 28. Investigator global assessment (IGA) is based on the investigator's assessment of the disease severity (Plaque thickening, Scaling and Erythema) using a 6-point scale (Clear,Almost clear, Mild,Moderate, Severe, and Very severe). The assessment represents the average lesion severity on the trunk and limbs. IGA can range between 1 (best) and 6 (worst). The assessment is based on the condition of the disease at the time of evaluation, and not in relation to the condition at a previous visit. | Day 28 |