Effect of LEO 90100 on the HPA Axis and Calcium Metabolism in Subjects With Extensive Psoriasis VulgarisExtensive Psoriasis Vulgaris
Condition: Psoriasis Vulgaris
MeSH terms: Psoriasis
Intervention: LEO 90100
Intervention description: Calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A Phase 2 Maximal Use Systemic Exposure (MUSE) study evaluating the safety and efficacy of
      LEO 90100 used once daily in subjects with extensive psoriasis vulgaris.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated informed consent obtained prior to any trial related activities
             (including any washout period)

          -  Age 18 years or above

          -  Either sex

          -  Any race or ethnicity

          -  Any skin type

          -  Attending a hospital out-patient clinic or the private practice of a dermatologist for
             treatment of psoriasis vulgaris

          -  At SV2 and Day 0 (Visit 1), a clinical diagnosis of psoriasis vulgaris of at least 6
             months duration involving the trunk and/or limbs and the scalp which is;

               -  amenable to topical treatment with a maximum of 120g of study medication per week

               -  of an extent of between 15 and 30% of the body surface area (BSA) excluding
                  psoriatic lesions of the face, genitals and skin folds

               -  including at least 30% scalp involvement

               -  of at least a moderate disease severity according to the investigators global
                  assessment (IGA)

          -  At SV2, a normal HPA axis function including a serum cortisol concentration above 5
             mcg/dl before ACTH-challenge and above 18 mcg/dl 30 minutes after ACTH-challenge

          -  At SV2, an albumin-corrected serum calcium below the upper reference range limit

          -  At SV2, females of child-bearing potential must have a negative urine pregnancy result

          -  Females of child-bearing potential must agree to use a highly effective method of
             contraception during the study. A highly effective method of birth control is defined
             as one which results in a low failure rate (less than 1% per year)

          -  Able to communicate with the investigator and understand and comply with the
             requirements of the study

        Exclusion Criteria:

          -  A history of allergic asthma, serious allergy or serious allergic skin rash

          -  Known or suspected hypersensitivity to component(s) of LEO 90100 or CORTROSYN
             (including cosyntropin/tetracosactide)

          -  Systemic treatment with corticosteroids (including inhaled and nasal steroids) within
             12 weeks prior to SV2

          -  Systemic treatment with biological therapies (whether marketed or not marketed), with
             a possible effect on psoriasis vulgaris within the following time period prior to Day
             0 (Visit 1);

               -  etanercept - within 4 weeks

               -  adalimumab, alefacept, infliximab - within 8 weeks

               -  ustekinumab - within 16 weeks

               -  other products - within 4 weeks/5 half-lives (whichever is longer)

          -  Subjects who have received treatment with any non-marketed drug substance (i.e. a drug
             which has not yet been made available for clinical use following registration) within
             4 weeks/5 half-lives (whichever is longer) prior to Day 0 (Visit 1)

          -  Systemic treatment with all other therapies with a possible effect on psoriasis
             vulgaris (e.g. retinoids, methotrexate, cyclosporine and other immunosuppressants)
             within 4 weeks prior to Day 0 (Visit 1)

          -  PUVA therapy within 4 weeks prior to Day 0 (Visit 1)

          -  UVB therapy within 2 weeks prior to day 0 (Visit 1).

          -  Topical treatment with corticosteroids or vitamin D analogues on any body location
             within 2 weeks prior to SV2

          -  Any topical treatment of psoriasis vulgaris on the trunk, limbs or scalp (except for
             emollients and non-medicated shampoos) within 2 weeks prior to Day 0 (Visit 1)

          -  Planned initiation of, or changes to, concomitant medication that could affect
             psoriasis vulgaris (e.g., betablockers, antimalarials, lithium, ACE inhibitors) during
             the study

          -  Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within
             4 weeks prior to SV2. Note: Stable doses of oral vitamin D supplementation ≤400 IU/day
             is permitted provided there are no dose adjustments during the study period

          -  Planned initiation of, or changes to concomitant medication that could affect calcium
             metabolism (e.g. antacids, thiazide and/or loop diuretics, antiepileptics) during the
             study

          -  Planned excessive exposure of area(s) to be treated with study medication to either
             natural or artificial sunlight (including tanning booths, sunlamps etc.) during the
             study

          -  Oestrogen therapy (including contraceptives), antidepressant medications and any other
             medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior
             to SV2

          -  Cytochrome P450 3A4 (CYP 3A4) inducers (e.g., barbiturates, phenytoin, rifampicin)
             within 4 weeks prior to SV2

          -  Systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., ketoconazole, itraconazole,
             metronidazole) within 4 weeks prior to SV2

          -  Topical cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., ketoconazole) within 2 weeks
             prior to SV2

          -  Non-nocturnal sleep patterns (e.g. night shift workers)

          -  Any of the following conditions, whether known or suspected:

               -  depression and endocrine disorders (e.g. Cushing's disease, Addison's disease,
                  diabetes mellitus) known to affect cortisol levels or HPA axis integrity

               -  disorders of calcium metabolism associated with hypercalcaemia

               -  cardiac disorders associated with abnormal QT intervals or rhythm disturbances
                  including clinically significant bradycardia or tachycardia

               -  severe renal insufficiency

               -  severe hepatic disorders

          -  Any clinically significant abnormality following blood pressure/heart rate measurement
             or review of screening laboratory tests (blood and spot urine samples) collected at
             SV2

          -  Any clinically significant abnormality following physical examination at SV1

          -  Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis

          -  Any of the following conditions present on the study treatment areas (trunk, limbs and
             scalp): 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, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin
             veins, ichthyosis, ulcers and wounds

          -  Other inflammatory skin disorders (e.g. seborrhoeic dermatitis and contact dermatitis)
             that may confound the evaluation of psoriasis vulgaris

          -  Current participation in any other interventional clinical trial

          -  Previously enrolled in this trial

          -  Known or suspected of not being able to comply with the trial protocol (e.g.,
             alcoholism, drug dependency or psychotic state)

          -  Females who are pregnant, wishing to become pregnant during the study or who are
             breast-feeding