An International, Multi-centre, Prospective, Non-controlled, Open, Single-group, 8-week Trial in Adolescent Subjects

Effect of Calcipotriol Plus Betamethasone Dipropionate Gel on the HPA Axis and Calcium Metabolism in Adolescent Subjects (Aged 12 to 16 Years, 11 Months) With Scalp and Body Psoriasis

An international, multi-centre, prospective, non-controlled, open, single-group, 8-week trial in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.

A phase 2 trial evaluating the safety and efficacy of once daily use of LEO 80185 gel containing calcipotriol 50 mcg/g plus betamethasone 0.5mg/g (as dipropionate) in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis.

Inclusion Criteria (all subjects):

• Clinical signs of psoriasis vulgaris on both the scalp and body (trunk and/or limbs)

• At SV2 and Visit 1, a clinical diagnosis of scalp and body (trunk and/or limbs) psoriasis which is:

  • of an extent of 10 to 35% of the body surface area (excluding psoriatic lesions of the face and sensitive areas. Sensitive areas include armpits, groin, under the breasts and in other skin folds around the genitals and buttocks), and
  • of at least moderate severity according to the investigator's global assessment of disease severity on the body.

• A serum albumin-corrected calcium level below the upper reference limit at SV2

Inclusion Criteria (for subjects performing HPA axis assessments):

• At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:

  • more than or equal to 20% of the scalp area, and
  • of at least moderate severity according to the investigator's global assessment of disease severity on the scalp.

• Subjects with a normal HPA axis function at SV2 including serum cortisol concentration above 5 mcg/dl before ACTH challenge and serum cortisol concentration above 18 mcg/dl 30 minutes after ACTH challenge.

Inclusion Criteria (for subjects not performing HPA axis assessments):

• At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:

  • more than or equal to 10% of the scalp area, and
  • of at least moderate severity according to the investigator's global assessment of disease severity on the scalp.

Exclusion Criteria (all subjects):

• Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on scalp and/or body psoriasis within the following time period prior to Visit 1 and during the trial:

  • etanercept - within 4 weeks prior to Visit 1
  • adalimumab, infliximab - within 2 months prior to Visit 1
  • ustekinumab - within 4 months prior to Visit 1
  • experimental products - within 4 weeks/5 half-lives (whichever is longer) prior to Visit 1

• Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g., retinoids, immunosuppressants, PUVA) within 4 weeks prior to Visit 1 (Day 0) or during the trial.

• UVB therapy within 2 weeks prior to Visit 1 or during the trial.

• Any topical treatment on the scalp and body (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to Visit 1 or during the trial.

• Systemic calcium, vitamin D supplements, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial.

• Planned initiation of, or changes to, concomitant medication that could affect psoriasis (e.g., betablockers, chloroquine, lithium, ACE inhibitors) during the trial.

• Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.

• Subjects with any of the following conditions present on the treatment areas on scalp and/or body: 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, acne vulgaris, acne rosacea, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers and wounds.

• Other inflammatory skin diseases that may confound the evaluation of scalp and/or body psoriasis.

• Planned excessive exposure to sun during the trial that may affect scalp and/or body psoriasis.

• Known or suspected severe renal insufficiency or severe hepatic disorders.

• Known or suspected disorders of calcium metabolism associated with hypercalcaemia.

• Any clinically significant abnormality following review of screening laboratory tests (blood and urine samples), physical examination or blood pressure/heart rate measurement performed at SV2.

• Current participation in any other interventional clinical trial.

• Previously enrolled in this trial.

• 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 a month prior to SV1 or longer, if the class of substance required a longer wash-out as defined above (e.g., biological treatments).

• Subjects or parent(s) or legal guardian known or suspected of being unlikely to comply with the Clinical Trial Protocol (e.g., alcoholism, drug dependency or psychotic state).

• Females who are pregnant, or of child-bearing potential and wishing to become pregnant during the trial, or who are breast-feeding.

• Females of child-bearing potential with positive pregnancy test at SV2.

• Subject (or their partner) not using an adequate method of contraception according to national requirements.

Exclusion Criteria (for subjects performing HPA axis assessments)

• A history of serious allergy, allergic asthma or serious allergic skin rash.
• Known or suspected hypersensitivity to any component of CORTROSYN® (including ACTH/cosyntropin/tetracosactide)
• Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
• Topical treatment with corticosteroids within 2 weeks prior to SV2 or during the trial.
• Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels levels or HPA axis integrity within 4 weeks prior to SV2 or during the trial.
• Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the trial.
• Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to SV2 or during the trial. Topical ketoconazole 2 weeks prior to SV2.
• Hypoglycemic sulfonamides within 4 weeks prior to SV2 or during the trial.
• Antidepressive medications within 4 weeks prior to SV2 or during the trial.
• Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
• Clinical signs or symptoms of Cushing's disease or Addison's disease.
• Subjects with diabetes mellitus.
• Known or suspected cardiac condition.
• Not following nocturnal sleep patterns.