Vasoconstriction
Conditions
Brief summary
The objective of this trial is to compare the vasoconstriction potential
Detailed description
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).
Interventions
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
DRUGMC2-01 Cream
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
DRUGClobetasol Propionate 0.05% Lotion
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
DRUGDesonide 0.05% Cream
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
DRUGVehicle
Single application, visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation
Sponsors
MC2 Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Visual assessments of potential skin blanching will be made independently by 2 trained observers, according to a grading scale (0 to 4)
Intervention model description
Single application, intra individual comparison on mini-test sites (n=7)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subjects aged 18 years to 50 years old having signed and dated an informed consent, 2. Non-smoker subjects, 3. 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)), 4. Subjects without signs of skin irritation/disease/disorders/symptoms or blemishes on test sites (e.g. erythema, dryness, roughness, scaling, scars, moles, sunburn), 5. Female subjects of non-childbearing potential defined as surgically sterile or post-menopausal (at least one year post cessation of menses), 6. 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, 7. Female subjects of childbearing potential must have a negative urine pregnancy test at screening visit and at Day 1 to continue, 8. Subjects willing and able to follow all the trial procedures and complete the whole trial, 9. Subjects affiliated to a social security system.
Exclusion criteria
1. Female subjects who are breastfeeding, 2. Use of topical corticosteroids on the test areas (forearms) within 4 weeks prior to the screening phase, 3. 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, 4. 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, 5. 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, 6. Subjects with a history of drug or alcohol abuse/addiction. 7. 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), 8. Subjects with obvious difference in skin color between arms, 9. 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, 10. 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), 11. Known or suspected hypersensitivity to any component(s) of Investigational Medical Product (IMP), 12. Subjects with current participation in any other interventional clinical, based on interview of the subject, 13. 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, 14. Previously enrolled in this clinical trial, 15. Subjects who do not accept to avoid strenuous physical activity nor alcohol intake during the study. 16. 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), 17. 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, 18. Subjects impossible to contact in case of emergency, 19. Subjects who are in an exclusion period in the National Biomedical Research Register of the French Ministry of Health at randomization, 20. Subjects under guardianship, hospitalized in a public or private institution, for a reason other than the research or subject deprived of freedom.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Day 2 | 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. |
| Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Day 2 | 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 |
Countries
France
Participant flow
Recruitment details
First Subject First Visit: 07-Nov-2018. Last Subject Last Visit: 23-Nov-2018
Pre-assignment details
The study consist of a screening period up to 15 day prior to randomization, a test period and a follow-up period. The study design is a within subject evaluation of the vasoconstriction properties of MC2-01 cream compared with vehicle cream and 5 other corticosteroids. All subjects received therefore a single treatment with all 7 products.
Participants by arm
| Arm | Count |
|---|---|
| MC2-01 Cream + Comparators Single application of 7 different treatments, where different sections on the arm was randomized to the following interventions:
1. \- MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream
2. \- Clobetasol Propionate 0.05% Lotion
3. \- Betamethasone Dipropionate 0.05% Cream
4. \- Triamcinolone Acetonide 0.1% Cream
5. \- Hydrocortisone Butyrate 0.1% Cream
6. \- Desonide 0.05% Cream
7. \- Vehicle Cream
to perform visual evaluation of skin blanching and local tolerability, physical examination and safety evaluation | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | MC2-01 Cream + Comparators | — |
|---|---|---|
| Age, Continuous | 34.36 years STANDARD_DEVIATION 6.57 | — |
| Fitzpatrick Skin Type I | 0 Participants | — |
| Fitzpatrick Skin Type II | 9 Participants | — |
| Fitzpatrick Skin Type III | 24 Participants | — |
| Fitzpatrick Skin Type IV | 3 Participants | — |
| Fitzpatrick Skin Type V | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 36 participants | — |
| Sex: Female, Male Female | 28 Participants | — |
| Sex: Female, Male Male | 8 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
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
Time frame: Day 2
Population: The local tolerance score is presented as number of participants with observed local reaction by trial product and severity.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | Blisters | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | No reaction | 36 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | Only Slight reaction | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | Only erythema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | Erythema with papules or oedema | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | Erythema, oedema with papules, oedema with vesicle | 0 Participants |
| MC2-01 Cream + Comparators | Compare Local Tolerability of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | Blisters | 0 Participants |
Primary
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.
Time frame: Day 2
Population: As the study design is a within subject evaluation of the vasoconstriction properties of MC2-01 cream compared with vehicle cream and 5 other corticosteroids, all 36 enrolled subjects received a single treatment with all 7 products.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | MC2-01 Cream | 1.66 score on a scale | Standard Deviation 0.57 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Clobetasol Propionate 0.05% Lotion | 3.05 score on a scale | Standard Deviation 0.65 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Betamethasone Dipropionate 0.05% Cream | 2.45 score on a scale | Standard Deviation 0.61 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Triamcinolone Acetonide 0.1% Cream | 1.92 score on a scale | Standard Deviation 0.89 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Hydrocortisone Butyrate 0.1% Cream | 2.06 score on a scale | Standard Deviation 0.7 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Desonide 0.05% Cream | 2.11 score on a scale | Standard Deviation 0.85 |
| MC2-01 Cream + Comparators | Comparison of the Vasoconstriction Potential (Skin Blanching Effect) of the MC2-01 Cream With Active Comparators and Vehicle | Vehicle Cream | 0.14 score on a scale | Standard Deviation 0.25 |