Evaluation of the Vasoconstriction Properties of MC2-01 Cream

Study Overview
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Brief Summary
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The objective of this trial is to compare the vasoconstriction potential

Detailed Description
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The objective of this trial is to compare the vasoconstriction potential (skin blanching effect) of MC2-01 cream with 5 comparators and MC2-01 vehicle using the human skin blanching test (McKenzie-Stoughton's test).

Official Title
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A Randomized, Evaluator Blinded, Within Subject, Single-Centre Evaluation of the Vasoconstriction Properties of MC2-01 Cream, Compared to 5 Other Corticosteroids in Healthy Subjects

Conditions
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Vasoconstriction

Intervention / Treatment
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* Drug: MC2-01 Cream
* Drug: Clobetasol Propionate 0.05% Lotion
* Drug: Betamethasone Dipropionate 0.05% Cream
* Drug: Triamcinolone Acetonide 0.1% Cream
* Drug: Hydrocortisone Butyrate 0.1% Cream
* Drug: Desonide 0.05% Cream
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18 years to 50 years old having signed and dated an informed consent, Non-smoker subjects, Subjects demonstrating adequate vasoconstriction to Diprolene® cream within 15 days prior to dosing (unoccluded application of Diprolene® cream for 4-6 hours must show a visual score of skin blanching of at least one unit (visual scale (0-4)), Subjects without signs of skin irritation/disease/disorders/symptoms or blemishes on test sites (e.g. erythema, dryness, roughness, scaling, scars, moles, sunburn), Female subjects of non-childbearing potential defined as surgically sterile or post-menopausal (at least one year post cessation of menses), Female subjects of childbearing potential who have been, in the opinion of the Investigator, using an approved method of birth control (e.g. oral contraception pill or patch, intra-uterine devices, contraceptive implants or vaginal rings, condoms, bilateral tubal ligation) at trial entry and agree to continue until the end of the last trial visit, Female subjects of childbearing potential must have a negative urine pregnancy test at screening visit and at Day 1 to continue, Subjects willing and able to follow all the trial procedures and complete the whole trial, Subjects affiliated to a social security system. Exclusion Criteria: Female subjects who are breastfeeding, Use of topical corticosteroids on the test areas (forearms) within 4 weeks prior to the screening phase, Use of systemic drugs which may interfere with the blanching reaction including, but not limited to, corticosteroids and other vasoactive drugs (nitrates derivatives, antihypertensive, phenylpropanolamine, diphenhydramine, pseudo-ephedrine, antihistamines, non-steroidal anti-inflammatory drug and aspirin/acetylsalicylic acid), within two weeks prior to screening visit, Use of any other medication would interfere with the trial results, in particular topical drugs applied on the test area within two weeks prior to screening visit, Subjects having a caffeine (i.e. coffee, cola, soft-drinks containing caffeine) intake greater than 500mg per day (1 cup of coffee contains approximately 85mg of caffeine) within one day prior to screening visit and until the end of the last visit of the test phase, Subjects with a history of drug or alcohol abuse/addiction. Abnormal pigmentation of the skin or skin type, that could, in any way, confound interpretation of the trail results (skin type V to VI on the Fitzpatrick scale), Subjects with obvious difference in skin color between arms, Subjects with any of the following conditions present on the test areas: viral (e.g. herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, atrophic skin, and striae atrophicae, fragility of skin veins, ichthyosis and ulcers, Any current systemic or cutaneous disease that could in any way confound interpretation of the trial results (e.g. atopic dermatitis, contact eczema, or psoriasis), Known or suspected hypersensitivity to any component(s) of Investigational Medical Product (IMP), Subjects with current participation in any other interventional clinical, based on interview of the subject, 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 the last 4 weeks prior to screening phase, Previously enrolled in this clinical trial, Subjects who do not accept to avoid strenuous physical activity nor alcohol intake during the study. In the opinion of the (sub)investigator, subjects who are unlikely to comply with the Clinical Trial Protocol (e.g. alcoholism, drug dependency or psychotic state), Subjects in close affiliation with the trial personnel (e.g. immediate family member or subordinate), subjects being a member of the clinical trial personnel, or being an employee of the sponsor or a Contract Research Organisation (CRO involved in the trial, Subjects impossible to contact in case of emergency, Subjects who are in an exclusion period in the National Biomedical Research Register of the French Ministry of Health at randomization, Subjects under guardianship, hospitalized in a public or private institution, for a reason other than the research or subject deprived of freedom.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Single application, intra individual comparison on mini-test sites (n=7)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MC2-01 Cream<br>Single application of MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream | Drug: MC2-01 Cream<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Calcipotriol + Betamethasone dipropionate cream;|
| Active Comparator: Clobetasol propionate 0.05% lotion<br>Single application of Clobetasol propionate 0.05%, | Drug: Clobetasol Propionate 0.05% Lotion<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Clobex;|
| Active Comparator: Betamethasone dipropionate 0.05% cream<br>Single application of Betamethasone dipropionate 0.05%, | Drug: Betamethasone Dipropionate 0.05% Cream<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Betamethasone Dipropionate;|
| Active Comparator: Triamcinolone acetonide 0.1% cream<br>Single application of Triamcinolone acetonide 0.1%, | Drug: Triamcinolone Acetonide 0.1% Cream<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Triamcinolone acetonide;|
| Active Comparator: Hydrocortisone Butyrate 0.1% cream<br>Single application of Hydrocortisone Butyrate 0.1% Cream | Drug: Hydrocortisone Butyrate 0.1% Cream<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Locoid® cream;|
| Active Comparator: Desonide 0.05% cream<br>Single application of Desonide 0.05% | Drug: Desonide 0.05% Cream<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Desowen® cream;|
| Placebo Comparator: Vehicle cream<br>Single application of Vehicle | Drug: Vehicle<br>* Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation<br>* Other names: Vehicle cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Blanching of the skin will be assessed individually by two trained observers blinded to treatment. The observers will score the blanching of the skin from 0-4 (0 = No change in color skin; 1 = Slight (barely visible) blanching; 3 = Obvious blanching; 4 = Blanching judged to be maximal). The results is presented as Mean ± SD. | Day 2 | 
| Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | The local tolerability of the creams will be assesed using a predefined scale: 0 = No reaction; 0.5 = Only slight erythema; 1 = Only erythema; 2 = Erythema with papules or oedema; 3 = Erythema, oedema with papules, oedema with vesicle; 4 = Blisters | Day 2 |