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

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00704262
• Collaborator: (none)
• Enrollment: 33
• Locations: 11
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Vulgaris	Drug: Calcipotriol plus hydrocortisone (LEO 80190)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Calcipotriol plus hydrocortisone (LEO 80190)	Drug: Calcipotriol plus hydrocortisone (LEO 80190); Once daily application

Outcome Measures

Primary Outcome Measures

1. The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 and 60 Minutes [At Week 4 (Day 28) and Week 8 (Day 56)]

   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.

2. Change in Albumin Corrected Serum Calcium [From baseline to Week 4, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

   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).

Secondary Outcome Measures

1. The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 Minutes [At Week 4 and Week 8]

   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.

2. The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 60 Minutes [At Week 4 and Week 8]

   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.

3. Serum Cortisol Concentration After 30 Minutes [At Week 4 and Week 8]

   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.

4. Serum Cortisol Concentration After 60 Minutes [At Week 4 and Week 8]

   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.

5. Change in Albumin Corrected Serum Calcium [From baseline to Week 2 and Week 6]

   Baseline was defined as the last assessment performed before study medication application.

6. Albumin Corrected Serum Calcium [At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

   The end of treatment data was defined as the last value recorded during the treatment phase (i.e. Week 4, 6, or 8).

7. Albumin Corrected Serum Calcium Values Above the Upper Limit of the Reference Range [At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

   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'.

8. Participants With "Controlled Disease" ("Clear" or "Almost Clear") According to the Investigator's Global Assessment of Disease Severity (IGA) of the Face [At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

   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)

9. Participants With "Controlled Disease" ("Clear" or "Almost Clear") According to the IGA of the Intertriginous Areas [At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

   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.

10. Overall Disease Severity of the Face According to the IGA [At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

    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)

11. Overall Disease Severity of Intertriginous Areas According to the IGA [At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)]

    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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Burke Pharmaceuticals	Hot Springs	Arkansas	United States	71913
2	Dermatology Research of Arkansas	Little Rock	Arkansas	United States	72205
3	Ameriderm Research	Ormond Beach	Florida	United States	32174
4	Somerset Skin Center	Troy	Michigan	United States	48084
5	Psoriasis Treatment Center of Central NJ	East Windsor	New Jersey	United States	08520
6	Virginia Clinical Research, Inc.	Norfolk	Virginia	United States	23507
7	The Guenther Dermatology Research Centre	London	Ontario	Canada	N6A3H7
8	Institute of Clinical Pharmacology Parexel International Gmbh	Berlin		Germany	12351
9	LCG Bioscience	Bourn	Cambridge	United Kingdom	CB3 7TR
10	ICON Development Solutions	Manchester		United Kingdom	M15 6SH
11	The Dermatology Centre, Hope Hospital	Manchester		United Kingdom	M6 8HD

Sponsors and Collaborators

• LEO Pharma

Investigators

• Principal Investigator: Rainard Fuhr, MD, PhD, Institute of Pharmacology Parexel International GmbH, Spandauer Damm 130, Haus 31, 14050 Berlin, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT00704262
• Other Study ID Numbers: LEO 80190-O23
• First Posted: Jun 24, 2008
• Last Update Posted: Oct 20, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Psoriasis; Hydrocortisone; Calcipotriene

Study Results

Participant Flow

Recruitment Details	The treatment phase was divided into two 4-week treatment periods during which the overall treatment duration had to be 28 days or 56 days. The participant was to leave the study if they were clear according to the investigator's global assessment of disease severity (IGA) of the face and of the intertriginous areas at Visit 3 (Day 28).

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190) ointment applied topically once daily for either 28 or 56 consecutive days on psoriasis vulgaris affected skin on the face and on the intertriginous areas. The ointment was not to be applied in the 24-hour period before Day 28 and Day 56 to avoid interference from the hydrocortisone with the adrenocorticotrophic hormone (ACTH) challenge test. Treatment was to be resumed after Visit 3, where applicable. The face was defined as: forehead including hairline, cheeks, nose, chin and ears (excluding the auditory meatus). In case of baldness or partial baldness, the forehead was to be estimated considering the standard or previous hairline. The intertriginous areas were defined as the axillae, the genito-femoral and inguinal folds, the inframammary folds, the intergluteal folds, and scrotum.
Period Title: Overall Study
STARTED	33
COMPLETED	31
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Overall Participants	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (15.9)
Sex: Female, Male (Count of Participants)
Female	14 42.4%
Male	19 57.6%
Region of Enrollment (participants) [Number]
Canada	8 24.2%
United States	7 21.2%
United Kingdom	11 33.3%
Germany	7 21.2%

Outcome Measures

1. Primary Outcome

Title	The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 and 60 Minutes
Description	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.
Time Frame	At Week 4 (Day 28) and Week 8 (Day 56)

Outcome Measure Data

Analysis Population Description

Per protocol analysis set (out of 33 participants who received treatment, 1 provided no ACTH challenge test data following start of treatment and 2 applied less than 1 gram of study treatment.)

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	30
>18 mcg/dL	29 87.9%
≤18 mcg/dL	1 3%

2. Primary Outcome

Title	Change in Albumin Corrected Serum Calcium
Description	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).
Time Frame	From baseline to Week 4, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

This evaluation was based on the safety analysis set that consists of all participants who received at least one application with study treatment (33 participants). The analysis only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Baseline	2.215
Week 4 (Day 28)	0.002
Week 8 (Day 56)	-0.045
End of Treatment (last value recorded)	-0.033

3. Secondary Outcome

Title	The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 30 Minutes
Description	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.
Time Frame	At Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Per protocol analysis set (out of 33 participants who received treatment, 1 provided no ACTH challenge test data following start of treatment and 2 applied less than 1 gram of study treatment.)

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	30
>18 mcg/dL	29 87.9%
≤18 mcg/dL	1 3%

4. Secondary Outcome

Title	The Adrenal Response to the ACTH Challenge Test Defined as the Serum Cortisol Concentration Obtained After 60 Minutes
Description	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.
Time Frame	At Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Per protocol analysis set (out of 33 participants who received treatment, 1 provided no ACTH challenge test data following start of treatment and 2 applied less than 1 gram of study treatment.)

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	30
>18 mcg/dL	30 90.9%
≤18 mcg/dL	0 0%

5. Secondary Outcome

Title	Serum Cortisol Concentration After 30 Minutes
Description	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.
Time Frame	At Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Per protocol analysis set (out of 33 participants who received treatment, 1 provided no ACTH challenge test data following start of treatment and 2 applied less than 1 gram of study treatment.)

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	30
Week 4 (Day 28)	25.29 (4.35)
Week 8 (Day 56)	25.93 (4.73)

6. Secondary Outcome

Title	Serum Cortisol Concentration After 60 Minutes
Description	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.
Time Frame	At Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Per protocol analysis set (out of 33 participants who received treatment, 1 provided no ACTH challenge test data following start of treatment and 2 applied less than 1 gram of study treatment.)

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	30
Week 4 (Day 28)	28.81 (3.48)
Week 8 (Day 56)	28.82 (5.30)

7. Secondary Outcome

Title	Change in Albumin Corrected Serum Calcium
Description	Baseline was defined as the last assessment performed before study medication application.
Time Frame	From baseline to Week 2 and Week 6

Outcome Measure Data

Analysis Population Description

This evaluation was based on all participants who received at least one application with study treatments, thus 33 participants were analyzed. The table only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Baseline	2.215 (0.077)
Week 2 (Day 14)	0.018 (0.095)
Week 6 (Day 42)	-0.013 (0.083)

8. Secondary Outcome

Title	Albumin Corrected Serum Calcium
Description	The end of treatment data was defined as the last value recorded during the treatment phase (i.e. Week 4, 6, or 8).
Time Frame	At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

This evaluation was based on the safety analysis set that consists of all participants who received at least one application with study treatment (33 participants). The analysis only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Week 2 (Day 14)	2.233 (0.079)
Week 4 (Day 28)	2.217 (0.074)
Week 6 (Day 42)	2.208 (0.096)
Week 8 (Day 56)	2.179 (0.085)
End of Treatment (last value recorded)	2.182 (0.081)

9. Secondary Outcome

Title	Albumin Corrected Serum Calcium Values Above the Upper Limit of the Reference Range
Description	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'.
Time Frame	At Week 2, Week 4, Week 6 and Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

This evaluation was based on all participants who received at least one application with study treatments, thus 33 participants were analyzed. The table only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Low	2 6.1%
Normal	30 90.9%
High	0 0%
Low	3 9.1%
Normal	30 90.9%
High	0 0%
Low	2 6.1%
Normal	26 78.8%
High	0 0%
Low	6 18.2%
Normal	21 63.6%
High	0 0%
Low	6 18.2%
Normal	27 81.8%
High	0 0%

10. Secondary Outcome

Title	Participants With "Controlled Disease" ("Clear" or "Almost Clear") According to the Investigator's Global Assessment of Disease Severity (IGA) of the Face
Description	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)
Time Frame	At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

This efficacy evaluation is based on the full analysis set that consists of all participants who received study treatment, thus 33 participants were analyzed. The analysis only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Controlled	21 63.6%
Non-controlled	12 36.4%
Controlled	19 57.6%
Non-controlled	9 27.3%
Controlled	23 69.7%
Non-controlled	10 30.3%

11. Secondary Outcome

Title	Participants With "Controlled Disease" ("Clear" or "Almost Clear") According to the IGA of the Intertriginous Areas
Description	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.
Time Frame	At Week 4, Week 8 and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

This efficacy evaluation is based on the full analysis set that consists of all participants who received study treatment, thus 33 participants were analyzed. The analysis only contains data from participants who attended the specific visits.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Controlled	20 60.6%
Non-controlled	13 39.4%
Controlled	19 57.6%
Non-controlled	9 27.3%
Controlled	23 69.7%
Non-controlled	10 30.3%

12. Secondary Outcome

Title	Overall Disease Severity of the Face According to the IGA
Description	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)
Time Frame	At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

A participant was to leave the study if he/she was clear according to the IGA of the face and after 4 weeks of treatment. Participants who still had psoriasis on the face after 4 weeks of treatment continued treatment for another 4-week period.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Clear	0 0%
Almost clear	0 0%
Mild	0 0%
Moderate	27 81.8%
Severe	6 18.2%
Very severe	0 0%
Clear	0 0%
Almost clear	12 36.4%
Mild	15 45.5%
Moderate	5 15.2%
Severe	1 3%
Very severe	0 0%
Clear	5 15.2%
Almost clear	16 48.5%
Mild	9 27.3%
Moderate	2 6.1%
Severe	1 3%
Very severe	0 0%
Clear	5 15.2%
Almost clear	15 45.5%
Mild	7 21.2%
Moderate	1 3%
Severe	0 0%
Very severe	0 0%
Clear	5 15.2%
Almost clear	14 42.4%
Mild	6 18.2%
Moderate	3 9.1%
Severe	0 0%
Very severe	0 0%
Clear	9 27.3%
Almost clear	14 42.4%
Mild	6 18.2%
Moderate	3 9.1%
Severe	1 3%
Very severe	0 0%

13. Secondary Outcome

Title	Overall Disease Severity of Intertriginous Areas According to the IGA
Description	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)
Time Frame	At baseline, Week 2, Week 4, Week 6, Week 8, and end of treatment (last value recorded i.e. Week 4, 6, or 8)

Outcome Measure Data

Analysis Population Description

A participant was to leave the study if they were clear according to the IGA of the intertriginous after 4 weeks of treatment. Participants who still had psoriasis on the intertriginous areas after 4 weeks of treatment continued treatment for another 4-week period.

Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
Measure Participants	33
Clear	0 0%
Almost clear	0 0%
Mild	0 0%
Moderate	19 57.6%
Severe	12 36.4%
Very severe	2 6.1%
Clear	0 0%
Almost clear	7 21.2%
Mild	16 48.5%
Moderate	9 27.3%
Severe	1 3%
Very severe	0 0%
Clear	5 15.2%
Almost clear	15 45.5%
Mild	10 30.3%
Moderate	2 6.1%
Severe	1 3%
Very severe	0 0%
Clear	4 12.1%
Almost clear	17 51.5%
Mild	5 15.2%
Moderate	2 6.1%
Severe	0 0%
Very severe	0 0%
Clear	7 21.2%
Almost clear	12 36.4%
Mild	7 21.2%
Moderate	2 6.1%
Severe	0 0%
Very severe	0 0%
Clear	10 30.3%
Almost clear	13 39.4%
Mild	7 21.2%
Moderate	2 6.1%
Severe	1 3%
Very severe	0 0%

Adverse Events

Time Frame	From baseline visit (Day -7 to -3) to Follow-up 1 (end of treatment +14 ± 2) and Follow-up 2 (end of treatment +28 ± 2).
Adverse Event Reporting Description	Follow-up 1 was only applicable if an adverse event (AE, serious or non-serious) classified as possibly or probably related to the study medication or not assessable in relation to the study medication was present at the participant's last on-treatment visit. This follow-up had to be performed 14 ±2 days after the participant's last on-treatment visit or until final outcome of the AE was determined, whichever came first. Follow-up 2 was only applicable in case of possible HPA axis suppression.
Arm/Group Title	Calcipotriol Plus Hydrocortisone (LEO 80190)
Arm/Group Description	Calcipotriol plus hydrocortisone (LEO 80190): Once daily application
All Cause Mortality
	Calcipotriol Plus Hydrocortisone (LEO 80190)
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Serious Adverse Events
	Calcipotriol Plus Hydrocortisone (LEO 80190)
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Other (Not Including Serious) Adverse Events
	Calcipotriol Plus Hydrocortisone (LEO 80190)
	Affected / at Risk (%)	# Events
Total	15/33 (45.5%)
Blood and lymphatic system disorders
Lymphadenopathy	1/33 (3%)
Ear and labyrinth disorders
Ear disorder	1/33 (3%)
Gastrointestinal disorders
Irritable bowel syndrome	1/33 (3%)
Nausea	2/33 (6.1%)
General disorders
Application site burning	1/33 (3%)
Application site pruritus	1/33 (3%)
Infections and infestations
Bronchitis	1/33 (3%)
Nasopharyngitis	3/33 (9.1%)
Otitis externa	1/33 (3%)
Pharyngitis	1/33 (3%)
Injury, poisoning and procedural complications
Face injury	1/33 (3%)
Joint sprain	1/33 (3%)
Ligament injury	1/33 (3%)
Metabolism and nutrition disorders
Gout	1/33 (3%)
Musculoskeletal and connective tissue disorders
Back pain	2/33 (6.1%)
Groin pain	1/33 (3%)
Joint stiffness	1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiomyolipoma	1/33 (3%)
Lipoma	1/33 (3%)
Nervous system disorders
Dizziness	1/33 (3%)
Headache	4/33 (12.1%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/33 (3%)
Skin and subcutaneous tissue disorders
Pruritus	1/33 (3%)
Vascular disorders
Hypertension	1/33 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Company acknowledges the investigators' right to publish the entire results of the study, irrespective of outcome. The Company retains the right to have any publication submitted to the Company for review at least 30 days prior to the same paper being submitted for publication or presentation. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.