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

Study Overview
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Brief Summary
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This is a phase 2, randomised, open-label, parallel-group, multicentre trial in which MC2-01 cream and calcipotriene [CAL]/betamethasone [BDP] ointment (comparator) is investigated in subjects 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, the MC2-01 cream will be compared to a marketed calcipotriene [CAL]/betamethasone dipropionate [BDP] ointment. The purpose of the trial, is to determine the pharmacokinetic parameters of MC2-01 cream and the comparator under maximum use conditions.

Official Title
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A Randomised, Open-label, Maximal Use Trial, Evaluating the Pharmacokinetic Profile of Active Ingredients and Their Metabolites After Application of MC2-01 Cream Compared With Active Comparator in Subjects With Extensive Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: MC2-01 Cream
* Drug: CAL/BDP combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided written informed consent. Generally healthy males or non-pregnant females, of any race or ethnicity, who are at least 18 years of age at the time of screening. At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 6 months duration involving scalp and body (trunk and/or limbs) that is amenable to topical treatment with a maximum of 100 g of trial medication per week. Have a Physician's Global Assessment [PGA] of severity of at least moderate on the trunk, limbs and/or scalp, at Visit 1/Day 0. Have a treatment area between 20% and 30% of the body surface area [BSA] on the trunk, limbs and/or scalp, excluding psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0. Exclusion Criteria: Current diagnosis of unstable forms of psoriasis Other inflammatory skin disease in the treatment area Pigmentation, extensive scarring, pigmented lesions or sunburn in the treatment areas Planned exposure to natural or artificial sunlight Phototherapy and ultraviolet B radiation within 4 weeks prior to Visit 1/Baseline and during the trial; Current or past history of 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 Visit 1/Day 0 during the trial period. 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 within 4 weeks prior to Vist 1/Day 0 and during the trial period; Use of topical treatments, except for emollients and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to Visit 1/Day 0 and during the trial period; Systemic treatment with biological therapies Initiation of, or expected changes to, concomitant medication that may affect psoriasis during the trial period; Depression and endocrine disorders known to affect cortisol levels or HPA axis integrity, non-nocturnal sleep patterns Systemic medication that suppresses the immune system within 4 weeks prior to the Visit 1/Day 0 and during the trial period; Clinical signs of skin infection with bacteria, viruses, or fungi; Known human immunodeficiency virus [HIV] infection; Known or suspected of hypersensitivity to any component of the test product or reference product; Any chronic or acute medical condition that may pose a risk to the safety of the subject, or may interfere with the assessment of safety or efficacy in this trial;

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MC2-01 Cream<br>MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%). | Drug: MC2-01 Cream<br>* MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)<br>|
| Active Comparator: CAL/BDP combination<br>CAL/BDP ointment (w/w 0.005%/0.064%). | Drug: CAL/BDP combination<br>* Calcipotriene/betamethasone (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 |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 4 | 
| Maximum Plasma Concentration (Cmax) of the Active Ingredient Calcipotriene | Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Calcipotriene. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 8 | 
| Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 4 | 
| Maximum Plasma Concentration (Cmax) of Active Ingredient Betamethasone Dipropionate | Geometric Mean for Maximum Plasma Concentration [Cmax] for the active ingredient Betamethasone Dipropionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 8 | 
| Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 4 | 
| Maximum Plasma Concentration (Cmax) of the Metabolite MC1080 | Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite MC1080. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 8 | 
| Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 4 | 
| Maximum Plasma Concentration (Cmax) of Metabolite Betamethasone 17-propionate | Geometric Mean for Maximum Plasma Concentration [Cmax] for the metabolite Betamethasone 17-propionate. Plasma concentration was measured at the following timepoints: pre-dose, 30 min, 1, 2, 3, 5 and 7 hours post-dose | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 4 Weeks of Treatment | The HPA axis evaluation is based on an Adrenocorticotropic hormone [ACTH] challenge test, defined by a 30 minutes ACTH stimulated cortisol value. Only subject with no HPA suppression at baseline were included in the analysis. The outcome measure lists the number of subjects with HPA suppression 30 minutes after ACTH challenge | Week 4 | 
| Number of Subjects With Hypothalamic-pituitary-adrenal [HPA] Suppression After 8 Weeks of Treatment | The HPA challenge test were only performed on subjects that were assigned to the MC2-01 cream group. Out of a total of 32 subjects, 5 subjects were excluded from the analysis as they had HPA suppression at baseline | Week 8 | 
| Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium | Changes from baseline of albumin-corrected serum calcium [mmol/L] | Baseline and week 4 | 
| Calcium Metabolism Evaluation in Albumin-corrected Serum Calcium | Changes from baseline in albumin-corrected serum calcium [mmol/L] | Baseline and week 8 | 
| Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion | Changes from baseline of 24-hour urinary calcium excretion [mmol/day] | Baseline and week 4 | 
| Calcium Metabolism Evaluation of 24-hour Urinary Calcium Excretion | Changes from baseline of 24-hour urinary calcium excretion [mmol/day] | Baseline and week 8 | 
| Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine | Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g) | Baseline and week 4 | 
| Calcium Metabolism Evaluation of the Ratio of Urinary Calcium to Creatinine | Changes from baseline in ratio of urinary calcium to creatinine defined as urinary calcium (mmol)/creatinine (g) | Baseline and week 8 |