Effect of Calcipotriol Plus Hydrocortisone Ointment on the Adrenal Hormone Balance and Calcium Metabolism in Patients With Psoriasis Vulgaris on the Face and Skin Folds

Study Overview
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Brief Summary
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There are few therapies suitable for the treatment of psoriasis on the face and skin folds. As these areas are sensitive, irritation and other adverse reactions are more common than elsewhere on the body. The purpose of the study is to monitor the effect of once daily treatment for up to 8 weeks of an ointment containing calcipotriol 25 mcg/g plus hydrocortisone 10 mg/g on the hypothalamic-pituitary-adrenal axis and on the calcium metabolism in patients with psoriasis vulgaris on the face and on the intertriginous areas

Official Title
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Effect of Calcipotriol Plus Hydrocortisone Ointment on the Hypothalamic-pituitary-adrenal (HPA) Axis and Calcium Metabolism in Patients With Psoriasis Vulgaris on the Face and on the Intertriginous Areas

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Calcipotriol plus hydrocortisone (LEO 80190)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of psoriasis vulgaris involving the face and the intertriginous areas Clinical diagnosis of psoriasis vulgaris on the trunk and/or limbs or earlier diagnosed with psoriasis vulgaris on the trunk and/or limbs An extent of psoriatic involvement on the face of at least 5 cm2 and the sum of all facial and intertriginous lesions at least 30 cm2 Treatment areas (face and intertriginous) amenable to topical treatment with a maximum of 100g ointment per week Disease severity of the face and intertriginous areas graded as moderate, severe or very severe according to the investigator´s global assessment of disease severity Patients with a normal HPA axis function: serum cortisol concentration above 5 mcg/dl before adrenocorticotropic hormone (ACTH: tetracosactid/cosyntropin) injection and serum cortisol concentration above 18 mcg/dl 30 min after ACTH (tetracosactid/cosyntropin) injection Albumin corrected serum calcium within reference range Females of childbearing potential have to use a highly effective method of contraception during the study (hormonal contraceptives on oestrogen basis are not allowed) Exclusion Criteria: A history of active allergy, asthma, allergic skin rash, or sensitivity to any medication (including ACTH/tetracosactid/cosyntropin) or to any component of the formulations being tested Systemic treatment with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (eg vitamin D analogues, retinoids)within 2 weeks prior to Visit 1. Stable treatment with methotrexate or fumaric acid is allowed Systemic treatment with corticosteroids within 12 weeks prior to Visit 1 Systemic use of biological treatments, whether marketed or not, directed against or with a potential effect on psoriasis vulgaris (eg. alefacept, efalizumab, etanercept, infliximab, adalimumab) within 12 weeks prior to Visit 1 Psoralen plus ultraviolet light A (PUVA) therapy or Grenz ray therapy within 4 weeks prior to Visit 1 Ultraviolet B (UVB) therapy within 2 weeks prior to Visit 1 Topical treatment with World Health Organization (WHO) group 2, 3 or 4 corticosteroids within 4 weeks prior to Visit 1 Topical treatment with WHO group 1 corticosteroids within 2 weeks prior to Visit 1 Any topical treatment of the face and intertriginous areas (except for emollients) within 2 weeks prior to Visit 1 Oestrogen therapy or any other medication known to affect cortisol levels or HPA-axis integrity within 4 weeks prior to Visit 1 Enzymatic inductors, systemic or topical cytochrome P450 inhibitors, hypoglycaemic sulfonamides or antidepressive medication within 4 weeks prior to Visit 1 Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis Patients with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds Other inflammatory skin diseases (e.g., seborrhoeic dermatitis, contact dermatitis and cutaneous mycosis) that may confound the evaluation of psoriasis vulgaris on the face or on the intertriginous areas Planned exposure to sun, Ultraviolet A (UVA) or UVB during the study that may affect the psoriasis vulgaris Clinical signs or symptoms of Cushing´s disease or Addison's disease Known or suspected severe renal insufficiency or severe hepatic disorders Known or suspected disorders of calcium metabolism associated with hypercalcaemia Known or suspected endocrine disorder that may affect the results of the ACTH challenge test

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcipotriol plus hydrocortisone (LEO 80190)<br> | Drug: Calcipotriol plus hydrocortisone (LEO 80190)<br>* Once daily application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 and 60 Minutes | The adrenal function was assessed by a rapid standard dose ACTH (tetracosactid/cosyntropin) challenge test. The ACTH challenge test consisted of a baseline blood (Day -7 to Day -3) sample taken at 8 a.m. (± 30 minutes). Following the baseline blood sample, an intravenous bolus injection of 250 mcg Synacthen®/Cortrosyn® was given at Time 0 (T = 0). Serum cortisol concentrations at 30 and 60 minutes after administration were taken and reflected the stimulation induced by tetracosactid/cosyntropin. ≤18 mcg/dL was considered low. | At Week 4 (Day 28) and Week 8 (Day 56) | 
| Change in Albumin Corrected Serum Calcium | Baseline was defined as the last assessment performed before study medication application. The end of treatment data was defined as the last value recorded during the treatment phase (i.e. Week 4, 6, or 8). | From baseline to Week 4, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 Minutes | The adrenal function was assessed by a rapid standard dose ACTH (tetracosactid/cosyntropin) challenge test. The ACTH challenge test consisted of a baseline blood (Day -7 to Day -3) sample taken at 8 a.m. (± 30 minutes). Following the baseline blood sample, an intravenous bolus injection of 250 mcg Synacthen®/Cortrosyn® was given at Time 0 (T = 0). Serum cortisol concentrations at 30 and 60 minutes after administration were taken and reflected the stimulation induced by tetracosactid/cosyntropin. ≤18 mcg/dL was considered low. | At Week 4 and Week 8 | 
| The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 60 Minutes | The adrenal function was assessed by a rapid standard dose ACTH (tetracosactid/cosyntropin) challenge test. The ACTH challenge test consisted of a baseline blood (Day -7 to Day -3) sample taken at 8 a.m. (± 30 minutes). Following the baseline blood sample, an intravenous bolus injection of 250 mcg Synacthen®/Cortrosyn® was given at Time 0 (T = 0). Serum cortisol concentrations at 30 and 60 minutes after administration were taken and reflected the stimulation induced by tetracosactid/cosyntropin. ≤18 mcg/dL was considered low. | At Week 4 and Week 8 | 
| Serum Cortisol Concentration After 30 Minutes | The adrenal function was assessed by a rapid standard dose ACTH (tetracosactid/cosyntropin) challenge test. The ACTH challenge test consisted of a baseline blood (Day -7 to Day -3) sample taken at 8 a.m. (± 30 minutes). Following the baseline blood sample, an intravenous bolus injection of 250 mcg Synacthen®/Cortrosyn® was given at Time 0 (T = 0). Serum cortisol concentrations at 30 and 60 minutes after administration were taken and reflected the stimulation induced by tetracosactid/cosyntropin. | At Week 4 and Week 8 | 
| Serum Cortisol Concentration After 60 Minutes | The adrenal function was assessed by a rapid standard dose ACTH (tetracosactid/cosyntropin) challenge test. The ACTH challenge test consisted of a baseline blood (Day -7 to Day -3) sample taken at 8 a.m. (± 30 minutes). Following the baseline blood sample, an intravenous bolus injection of 250 mcg Synacthen®/Cortrosyn® was given at Time 0 (T = 0). Serum cortisol concentrations at 30 and 60 minutes after administration were taken and reflected the stimulation induced by tetracosactid/cosyntropin. | At Week 4 and Week 8 | 
| Change in Albumin Corrected Serum Calcium | Baseline was defined as the last assessment performed before study medication application. | From baseline to Week 2 and Week 6 | 
| Albumin Corrected Serum Calcium | The end of treatment data was defined as the last value recorded during the treatment phase (i.e. Week 4, 6, or 8). | At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 
| Albumin Corrected Serum Calcium Values Above the Upper Limit of the Reference Range | The table summarizes the shifts in albumin corrected serum calcium versus the normal range. The end of treatment data was defined as the last value recorded for the parameter during the treatment phase of the study (i.e. Week 4, 6, or 8). The normal reference range for the albumin corrected serum calcium was defined as 2.1-2.64 mmol/L (8.4-10.6 mg/L). The value below this level was considered 'low', while the value above this range was considered 'high'. | At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 
| Participants With Controlled Disease (Clear or Almost Clear) According to the Investigator's Global Assessment of Disease Severity (IGA) of the Face | Controlled disease was defined as the following (P=Plaque thickening, S=Scaling, E=Erythema) Clear (Plaque thickening=no elevation/thickening of normal skin, S=no evidence of scaling, E= none/hyperpigmentation/residual red coloration) or Almost clear (P=none/possible thickening but difficult to ascertain whether there is a slight elevation above normal skin level, S=none/residual surface dryness and scaling, E=light pink coloration) (last value recorded i.e. Week 4, 6, or 8) | At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 
| Participants With Controlled Disease (Clear or Almost Clear) According to the IGA of the Intertriginous Areas | Controlled disease was defined as the following: Clear (Infiltration = no elevation or thickening of normal skin, Erythema = normal skin colour or hyperpigmentation) or Almost clear (Infiltration = no elevation or thickening of normal skin, Erythema = faint pink colour) The end of treatment data was defined as the last value recorded for the efficacy measure. | At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 
| Overall Disease Severity of the Face According to the IGA | 6-category scale based on plaque thickening (P), Scaling (S), Erythema (E). Clear (P=no elevation/thickening of normal skin, S=no evidence of scaling, E=none/hyperpigmentation/residual red coloration) Almost clear (P=none/possible thickening but difficult to ascertain whether there is a slight elevation above normal skin level, S=none/residual surface dryness and scaling, E=light pink coloration) Mild (P=slight but definite elevation, S=fine scales partially/mostly covering lesions, E=light red coloration) Moderate (P=moderate elevation with rounded or sloped edges, S=most lesions at least partially covered, E=definite red coloration) Severe (P =marked elevation typically with hard or sharp edges, S=non-tenacious scale predominates, covering most or all of the lesions, E=very bright red coloration) Very severe (P=very marked elevation typically with hard or sharp edges, S=thick tenacious scale covers most or all of the lesions, E=extreme red coloration, deep red coloration) | At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8) | 
| Overall Disease Severity of Intertriginous Areas According to the IGA | The assessment of the disease severity of the intertriginous areas was made using the 6-category scale; clear, almost clear, mild, moderate, severe, very severe. Clear (Infiltration = no elevation or thickening of normal skin, Erythema = normal skin colour or hyperpigmentation) Almost clear (Infiltration = no elevation or thickening of normal skin, Erythema = faint pink colour) Mild (Infiltration = slight, subtle thickening or infiltration, only marginally increased from normal skin, Erythema = light pink colour) Moderate (Infiltration = palpable thickening or infiltration without elevation, Erythema = definite pink colour) Severe (Infiltration = palpable thickening or infiltration with elevation, Erythema = very bright red coloration) Very severe (Infiltration = marked thickening or infiltration with rounded or sloped edges, Erythema = bright deep red coloration) | At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8) |