Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel Compared With Tacalcitol Ointment and the Gel Vehicle Alone in Patients With Psoriasis Vulgaris

Study Overview
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Brief Summary
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This study will compare efficacy and safety of once daily treatment of calcipotriol plus betamethasone dipropionate gel (LEO 80185) with tacalcitol ointment and LEO 80185 vehicle alone in subjects with psoriasis vulgaris. Subjects will be treated for up to 8 weeks followed by an observation period of up to 8 weeks to investigate the occurence and the time to relapse and occurence of rebound after discontinuation of the investigational products. Only subjects with controlled disease will be considered for this observation phase of the study. Controlled disease is defined as Clear or Almost Clear severity category based on Investigator's global assessment (IGA).

Official Title
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A Phase 3 Study Comparing a Gel Containing Calcipotriol 50 mcg/g Plus Betamethasone 0.5 mg/g (as Dipropionate) With Tacalcitol Ointment (4 mcg/g) and Gel Vehicle, Used Once Daily in the Treatment of Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: calcipotriol and betamethasone (LEO 80185 gel)
* Drug: LEO 80185 vehicle
* Drug: Tacalcitol ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent to be obtained prior to any trial related procedure, including wash-out Clinical diagnosis of psoriasis vulgaris involving trunk and/or arms and/or legs amenable to treatment with a maximum of 100 g of LEO 80185 gel per week or 10 g per day of tacalcitol ointment Disease severity graded moderate, severe or very severe according to the Investigator's global assessment (IGA) of disease severity A minimum PASI score for extent of 2 in at least one body region (i.e.psoriasis affecting at least 10% of arms, and/or 10% of trunk, and/or 10% of legs) Subjects aged 18 years or above Either sex Any ethnic origin Attending hospital outpatient clinic or the private practice of a dermatologist Exclusion Criteria: Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, infliximab, adalimumab) within 3 months prior to randomisation Systemic treatment with all other therapies than biologics, with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within 4 weeks prior to randomisation Systemic treatment with Vitamin D preparations above 500 IU per day PUVA or Grenz ray therapy within 4 weeks prior to randomization UVB therapy within 2 weeks prior to randomisation Any topical treatment of the trunk/limbs (except for emollients) within 2 weeks prior to randomisation Topical treatment for other relevant skin disorders on the face and flexures (e.g., facial and flexural psoriasis, eczema) with potent or very potent (WHO group III-IV) corticosteroids or vitamin D analogues within 2 weeks prior to randomisation Topical treatment for other relevant skin disorders on the scalp (e.g. scalp psoriasis) with very potent (WHO group IV) corticosteroids or vitamin D analogues within 2 weeks prior to randomisation Planned initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, ACE inhibitors, anti-malaria drugs, lithium) during the study Current diagnosis of erythrodermic, exfoliative or pustular psoriasis Subjects with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atro-phicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds Known or suspected disorders of calcium metabolism associated with hypercalcaemia Known or suspected severe renal insufficiency or severe hepatic disorders Known or suspected hypersensitivity to component(s) 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 randomisation, except for biologics (3 months) Planned exposure to sun during the study that may affect psoriasis vulgaris Previously randomised to this study Subjects known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychotic state) Females of child-bearing potential wishing to become pregnant during the study, or are breast-feeding, or not using an adequate method of contraception during the study Females of child-bearing potential with positive pregnancy test at Visit 1

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: calcipotriol and betamethasone (LEO 80185 gel)<br>* Once daily application<br>|
| Active Comparator: 2<br> | Drug: Tacalcitol ointment<br>* Once daily application<br>|
| Placebo Comparator: 3<br> | Drug: LEO 80185 vehicle<br>* Once daily application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8 |  | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4 |  | Week 4 | 
| The Percentage Change in PASI From Baseline to Week 8 | PASI is Psoriasis Area and Severity Index and is based on the investigator's assessment of extent and severity of the disease. It can range from 0 (best) to 64.8 (worst). | Baseline, Week 4 and 8 | 
| Subjects With Relapse During the Study | Among subjects with controlled disease at week 8 relapse was defined as PASI exceeding the baseline PASI value minus 50% of the reduction in PASI obtained from the baseline visit to the last on-treatment visit | Week 8-16 | 
| Subjects With Rebound During the Study |  | Week 8-16 |