A Maximal Use Trial Evaluating the Pharmacokinetic Profile of MC2-01 Cream in Adolescent Subjects

Study Overview
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Brief Summary
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This is a phase 2, open-label, single-group, multicentre trial in which the investigational product, MC2-01 cream, is investigated in adolescent subjects (age 12 to 16 years, 11 months) with clinically diagnosed extensive psoriasis vulgaris.

Detailed Description
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The MC2-01 cream is designed for optimal patient satisfaction - it quickly absorbs into the skin leaving it nicely moisturized allowing patients to move on with daily routines. In this trial, subjects who fulfil all inclusion and exclusion criteria are enrolled in the trial and will apply one dose of trial medication topically once daily for 8 weeks. The purpose of the trial, is to determine the and pharmacokinetic parameters of MC2-01 cream in adolescent subjects under maximum use conditions.

Official Title
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A Multicentre, Open-label, Single-group Maximal Use Trial, Evaluating the Safety and Pharmacokinetic Profile of the Active Ingredients and Their Metabolites After Application of MC2-01 Cream in Adolescents With Extensive Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: MC2-01 cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The parent(s), or legal guardian(s) (according to national law) have provided written informed consent following their receipt of verbal and written information about the trial The subject (according to national law) has provided written assent to the trial following their receipt of verbal and written information about the trial Generally healthy males or non-pregnant females, of any race or ethnicity, who are between 12 to 16 years, 11-month-old at Screening Visit 1 (SV1) At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 6 months duration involving body (trunk and/or limbs), with or without scalp Have a treatment area between 10% and 30% of the Body Surface Area (BSA) on the body (trunk and/or limbs) and scalp, excluding psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0 Have a Physician's Global Assessment (PGA) of at least moderate severity on the treatment area A normal HPA axis function including a serum cortisol concentration above 4,5 mcg/dl before ACTH-challenge and equal or above 18 mcg/dl 30 minutes after ACTH challenge, at Screening Visit 2 (SV2) A serum albumin-corrected calcium below the upper reference limit at SV2 Exclusion Criteria: Have a current diagnosis of unstable forms of psoriasis, including erythrodermic or pustular psoriasis Other inflammatory skin disease in the treatment area that may confound the evaluation of the psoriasis vulgaris Presence of infections in the treatment area or skin manifestations or atrophic skin, atrophic striae, skin vein fragility, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds in the treatment area Presence of pigmentation, extensive scarring, pigmented lesions or sunburn in the treatment areas, which could interfere with the rating of efficacy parameters Planned excessive or prolonged exposure to either natural or artificial sunlight Use of phototherapy (psoralen + ultraviolet A radiation and ultraviolet B radiation within 4 weeks prior to SV2 and during the trial Current or past history of disorders of calcium metabolism associated with hypercalcemia, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 4 weeks prior to SV2 Planned initiation of, or changes to concomitant medication that could affect calcium metabolism during the trial; Planned initiation of, or changes to, concomitant estrogen therapy during the trial Strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors or inducers within 4 weeks prior to SV2 and during the trial Use of topical treatments, except for emollients and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to SV2 and during the trial Systemic treatment with biological therapies, with a possible effect on psoriasis vulgaris within the following time period prior to SV2 and during the trial Initiation of, or expected changes to, concomitant medication that may affect psoriasis during the trial Any of the following conditions, whether known or suspected; Clinically diagnosed depression where the subject is in current treatment with medication approved for treatment of depression; Endocrine disorders known to affect cortisol levels or HPA axis integrity; Non-nocturnal sleep patterns Use of systemic medication that suppresses the immune system and other systemic chemotherapeutic antineoplastic therapy within 4 weeks prior to the SV2 and during the trial Use of live vaccines 4 weeks before SV2 and during the trial Have clinical signs of skin infection with bacteria, viruses, or fungi Known human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C Known or suspected of hypersensitivity to any component of the test product Known allergic asthma, serious allergies or allergies where recurrent acute or chronic treatment is necessary Have any chronic or acute medical condition that, in the opinion of the investigator, may pose a risk to the safety of the subject, or may interfere with the assessment of safety or efficacy in this trial Require the use of any concomitant medication that, in the investigator's opinion, has the potential to cause an adverse effect when given with the Investigational Product (IP) or will interfere with the interpretation of the trial results Subject with known abnormal reduction in muscle mass, as judged by the investigator

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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: MC2-01 cream<br>MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream. One application daily for 8 weeks | Drug: MC2-01 cream<br>* MC2-01 cream (Calcipotriene/betamethasone dipropionate, w/w 0.005%/ 0.064%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HPA (Hypothalamic-pituitary-adrenal) Axis Suppression at Week 4 | Adrenal function will be assessed in a challenge test with an intravenous dose of cosyntropin. Measurement of serum cortisol levels pre- and post- stimulation is an accepted standard method used to evaluate adrenal suppression. The test consists of an initial blood sampling. Following the blood sample, an intravenous bolus injection of 0.25 mg cosyntropin is given. The serum cortisol concentration 30 min. after will reflect stimulation of the adrenal glands induced by cosyntropin. HPA axis suppression is define as serum cortisol below 18 µg/dL | Week 4 | 
| Number of Participants With HPA (Hypothalamic-pituitary-adrenal) Axis Suppression at Week 8 | Adrenal function will be assessed in a challenge test with an intravenous dose of cosyntropin. Measurement of serum cortisol levels pre- and post- stimulation is an accepted standard method used to evaluate adrenal suppression. The test consists of an initial blood sampling. Following the blood sample, an intravenous bolus injection of 0.25 mg cosyntropin is given. The serum cortisol concentration 30 min. after will reflect stimulation of the adrenal glands induced by cosyntropin. HPA axis suppression is define as serum cortisol below 18 µg/dL | Week 8 | 
| Change in S-Calcium Metabolism at Week 4 | Change from Baseline to Week 4 in albumin-corrected S-calcium | Week 4 | 
| Change in S-Calcium Metabolism at Week 8 | Change from Baseline to Week 8 in albumin-corrected S-calcium | Week 8 | 
| Change in U-Calcium Metabolism at Week 4 | Change from Baseline to Week 4 in Urinary Calcium/Creatinine ratio (mol/mol) | Week 4 | 
| Change in U-Calcium Metabolism at Week 8 | Change from Baseline to Week 8 in Urinary Calcium/Creatinine ratio (mol/mol) | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Maximum Plasma Concentration [Cmax] of Betamethasone 17-propionate at Week 4 | The Maximum Plasma Concentration [Cmax] of the metabolite of BDP, betamethasone 17-propionate measured at Week 4. | Week 4 | 
| Time to Maximum Plasma Drug Concentration [Tmax] of Betamethasone 17-propionate at Week 4 | Time to maximum plasma drug concentration [Tmax] of the metabolite of BDP, betamethasone 17-propionate measured at Week 4. | Week 4 |