Evaluation of Potential Development of Photoallergic Skin Reaction After Use of MC2-01 Cream

Study Overview
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Brief Summary
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This trial is a 6-week, Randomized study evaluating the potential of MC2-01 Cream to induce a photoallergic skin reaction in Healthy subjects, using a controlled photopatch test design.

Detailed Description
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The study evaluates the potential of MC2-01(CAL/BDP 0.005/0.064 w/w%) Cream to induce a photoallergic skin reaction. Because MC2-01 Cream is formulated for topical use and has shown to absorb light within the range of natural sunlight, it is necessary to determine the potential of this product to cause a photoallergic reaction after application to the skin.

Official Title
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A 6-Week, Randomized Study to Evaluate the Potential of MC2-01 Cream to Induce Photoallergic Skin Reaction in Healthy Subjects, Using a Controlled Photopatch Test Design

Conditions
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Photoallergy

Intervention / Treatment
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* Drug: Induction: Application of MC2-01 Cream, irradiation
* Drug: Induction: Application of MC2-01 Cream, no irradiation
* Drug: Induction: Applications of MC2-01 vehicle, irradiation
* Drug: Induction: Applications of MC2-01 vehicle, no irradiation
* Drug: Challenge: Application of MC2-01 Cream, irradiation
* Drug: Challenge: Application of MC2-01 Cream, no irradiation
* Drug: Challenge: Applications of MC2-01 vehicle, irradiation
* Drug: Challenge: Applications of MC2-01 vehicle, no irradiation
* Drug: Challenge: Control, irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a healthy male or female Is 18 years of age or older Agree not to participate in any clinical or patch test studies at Day 1 through study completion Females or childbearing potential must use a highly effective method of contraception for one month prior to Screening and until the end of study visit has been performed In the case of a female of childbearing potential, has a negative urine pregnancy test on Day 1 prior to randomization and are willing to submit to a urine pregnancy test at the end of study In the case of a female of childbearing potential, has had a hysterectomy or is postmenopausal Is free of any systemic or dermatological disorder, which, in the opinion of the Investigator, will interfere with the study results or increase the risk of AEs. Has uniformly-colored skin on the intrascapular region of the back which will allow discernment of erythema, and has Fitzpatrick skin types I, II or III Complete a medical screening procedure Read, understand and sign an informed consent Exclusion Criteria: Has a history of photosensitivity or photoallergy Has any visible skin disease at the application site which, in the opinion of the Investigator, will interfere with the evaluation of the test site reaction Current or past history of hypercalcemia, vitamin D toxicity, severe renal insufficiency or severe hepatic disorders Is using systemic/topical corticosteroids within 3 weeks prior to and/or during the study or systemic/topical antihistamines 72 hours prior to and during the study Is not willing to refrain from using systemic/topical anti-inflammatory analgesics (81 mg aspirin and occasional use of acetaminophen will be permitted) Are taking medication known to cause phototoxic reaction Is using medication which, in the opinion of the Investigator, will interfere with the study results Is unwilling or unable to refrain from the use of sunscreens, cosmetics, creams, ointments, lotions or similar products on the back during the study Has psoriasis and/or atopic dermatitis/eczema Has a known sensitivity or allergy to constituents of the materials being evaluated Is a female who is pregnant, plans to become pregnant during the study, or is breast feeding a child Has damaged skin in or around the test sites, including sunburn, excessively deep tans, uneven skin tones, tattoos, scars excessive hair, numerous freckles or other disfigurations of the test site Has received treatment for any type of internal cancer within 5 years prior to study entry Has a history of, or are currently being treated for skin cancer and/or hepatitis Has a history or, or is currently being treated for diabetes Has any condition that might compromise study results Is expected to sunbathe or use tanning salons during the study Has a history of adverse response to UV-sun lamps/sunlight exposure Is currently participating in any clinical testing Has any known sensitivity to adhesives Has received any investigational drug(s) within 28 days from Day 1

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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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: The study consist of an Induction phase, where treatments (MC2-01 Cream, MC2-01 vehicle) were applied to 2 test sites each (n=4), followed by irradiation/non-irradiation and evaluation 24, 48 or 72 hours post-irradiation. This was repeated in total 6 times over an 3 weeks period. The induction phase was followed by a challenge phase, where treatments (MC2-01 Cream, MC2-01 vehicle) were applied to each two naive test sites and another naive test site was untreated. 24 hours of product application, one of each test sites (MC2-01 Cream, MC2-01 vehicle) + the untreated test site were irradiated. Possible changes in dermal reaction (erythema and edema) was evaluated at all 5 test sites, 24, 48 and 72 hours post-irradiation.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction:MC2-01 Cream, irradiation<br>Applications with MC2-01 Cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%), followed by irradiation | Drug: Induction: Application of MC2-01 Cream, irradiation<br>* Repeated applications of MC2-01 Cream (CAL/BDP, 0.005%/0.064%), followed by irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema, edema and other signs of cutaneous irritation<br>|
| Experimental: Induction: MC2-01 Cream, no irradiation<br>Applications with MC2-01 Cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%), no irradiation | Drug: Induction: Application of MC2-01 Cream, no irradiation<br>* Repeated applications of MC2-01 Cream, CAL/BDP, 0.005%/0.064%, no irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema, edema and other signs of cutaneous irritation<br>|
| Experimental: Induction: MC2-01 vehicle, irradiation<br>Applications with MC2-01 vehicle, followed by irradiation | Drug: Induction: Applications of MC2-01 vehicle, irradiation<br>* Repeated applications of MC2-01 cream, followed by irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema, edema and other signs of cutaneous irritation<br>|
| Experimental: Induction: MC2-01 vehicle, no irradiation<br>Applications with MC2-01 vehicle, no irradiation | Drug: Induction: Applications of MC2-01 vehicle, no irradiation<br>* Repeated applications of MC2-01 vehicle, no irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema, edema and other signs of cutaneous irritation<br>|
| Experimental: Challenge: MC2-01 Cream, irradiation<br>Application with MC2-01 Cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%), followed by irradiation | Drug: Challenge: Application of MC2-01 Cream, irradiation<br>* Single application of MC2-01 Cream (CAL/BDP, 0.005%/0.064%), followed by irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema and edema<br>|
| Experimental: Challenge: MC2-01 Cream, No irradiation<br>Application with MC2-01 Cream (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%), no irradiation | Drug: Challenge: Application of MC2-01 Cream, no irradiation<br>* Single application of MC2-01 Cream (CAL/BDP, 0.005%/0.064%), no irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema and edema<br>|
| Experimental: Challenge: MC2-01 vehicle, irradiation<br>Application with MC2-01 vehicle, followed by irradiation | Drug: Challenge: Applications of MC2-01 vehicle, irradiation<br>* Single application of MC2-01 vehicle, followed by irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema and edema<br>|
| Experimental: Challenge: MC2-01 vehicle, no irradiation<br>Application with MC2-01 vehicle, no irradiation | Drug: Challenge: Applications of MC2-01 vehicle, no irradiation<br>* Single application of MC2-01 vehicle, no irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema and edema<br>|
| Experimental: Challenge: Control, irradiation<br>No application, but irradiation | Drug: Challenge: Control, irradiation<br>* No application, but irradiation. Visual evaluation of application site using a visual scale that rated the degree of erythema and edema<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-subject Comparison of Dermal Reaction by the Overall Numeric Rating of Erythema and Edema at 5 Defined Test Sites, After Application of MC2-01 Cream, MC2-01 Vehicle or Untreated at Defined Test Sites, Followed by Irradiation. | After an induction phase, where subjects were treated with MC2-01 Cream, MC2-01 vehicle and irradiation, the challenge phase was initiated. MC2-01 Cream and MC2-01 vehicle was applied to each two naive test sites. Another naive test site was untreated. 24 hours after product application, one of each test site (MC2-01 Cream, MC2-01 vehicle) + the untreated site were irradiated. Possible changes in dermal reaction (erythema and edema) was evaluated at all 5 test sites 24, 48 and 72 hours post-irradiation and these evaluations are the outcome measure of the study. The following visual scores was used to express the response observed at each timepoints: Erythema: 0-3 where 0 represents no reaction and 3 represents marked/severe erythema. Edema: 0-2 where 0 represents no reaction and 2 represents definite edema with erosion/vesiculation. The diagnosis of photosensitization response will be made by the investigator based on review of the scored skin responses of both erythema and edema. | 24 hours | 
| Within-subject Comparison of Dermal Reaction by the Overall Numeric Rating of Erythema and Edema at 5 Defined Test Sites, After Application of MC2-01 Cream, MC2-01 Vehicle or Untreated at Defined Test Sites, Followed by Irradiation. | After an induction phase, where subjects were treated with MC2-01 Cream, MC2-01 vehicle and irradiation, the challenge phase was initiated. MC2-01 Cream and MC2-01 vehicle was applied to each two naive test sites. Another two naive test sites were untreated. 24 hours of product application, one of each test site (MC2-01 Cream, MC2-01 vehicle and untreated) were irradiated. Possible changes in dermal reaction (erythema and edema) was evaluated at all 6 test sites, 24, 48 and 72 hours post-irradiation and these evaluations are the outcome measure of the study. The following visual scores was used to express the response observed at each timepoints: Erythema: 0-3 where 0 represents no reaction and 3 represents marked/severe erythema. Edema: 0-2 where 0 represents no reaction and 2 represents definite edema with erosion/vesiculation. The diagnosis of photosensitization response will be made by the investigator based on review of the scored skin responses of both erythema and edema. | 48 hours | 
| Within-subject Comparison of Dermal Reaction by the Overall Numeric Rating of Erythema and Edema at 5 Defined Test Sites, After Application of MC2-01 Cream, MC2-01 Vehicle or Untreated at Defined Test Sites, Followed by Irradiation. | After an induction phase, where subjects were treated with MC2-01 Cream, MC2-01 vehicle and irradiation, the challenge phase was initiated. MC2-01 Cream and MC2-01 vehicle was applied to each two naive test sites. Another two naive test sites were untreated. 24 hours of product application, one of each test site (MC2-01 Cream, MC2-01 vehicle and untreated) were irradiated. Possible changes in dermal reaction (erythema and edema) was evaluated at all 6 test sites, 24, 48 and 72 hours post-irradiation and these evaluations are the outcome measure of the study. The following visual scores was used to express the response observed at each timepoints: Erythema: 0-3 where 0 represents no reaction and 3 represents marked/severe erythema. Edema: 0-2 where 0 represents no reaction and 2 represents definite edema with erosion/vesiculation. The diagnosis of photosensitization response will be made by the investigator based on review of the scored skin responses of both erythema and edema. | 72 hours |