A Photoxicity and Photoallergy Study of a Developmental Face Cream, Serum and Lotion

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the absence of sensitisation and irritation potential of a product when applied to the skin and exposed to ultraviolet (UV) radiation. Photo-sensitisation potential will primarily be evaluated through a subsequent semi-occluded application and UV exposure (challenge phase) after a 2-week rest period. Photo-irritation potential will primarily be evaluated through the repeated occluded application and UV exposure of the study products over 3 weeks (induction phase).

Detailed Description
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A single-center, randomised, evaluator (single) blind study in healthy adult participants aged 18 to 65 years with no dermatological disorders to evaluate the cutaneous photo- irritation and photo-sensitisation potential of three cosmetic facial skincare products. During Screening (Visit 1), the participants will sign an informed consent, will undergo dermatological assessment to ensure they have no dermatoses on their dorsum that might impact their safety, Fitzpatrick Phototype of II to IV and colorimetry analysis of their skin type using the Individual Typology Angle, which will be used to estimate minimal erythemal dose (MED). At Visit 2, the eligible participants will undergo MED irradiation where the participant will be administered a series of 6 controlled doses of UV radiation. At Visit 3, the participants will undergo MED determination, where a trained evaluator will evaluate the exposed skin to determine the lowest dose of UV radiation required to induce uniform, unambiguous erythema for signs of visible erythema. Further, the study will progress in 3-phases: Induction phase, Rest Phase and Challenge Phase. The Induction phase (3 weeks: Visit 4 to Visit 18); at visit 4, the area for applying 2 consecutive patches will be designated between the scapula and waistline. A controlled amount (0.02 mL/cm^2) of each study product will be randomly assigned within the patch system of each participant into the appropriate separate cell (3 cells for each of the test products and 1 cell for the saline solution). Every Monday, patch sites will be evaluated, 2 patches will be applied, post 24 hours (Tuesday) the patches will be removed, patch sites can be cleaned, patch sites will be evaluated, test products/ saline will be re-applied and 1 of the 2 sites will be irradiated with 2.5 Joules per centimetre square UVA radiation with a Schott UG11+WG335 filter (or equivalent) in place, and then with 0.3 MEDs of UVA+UVB radiation (filters UG11+WG320). The sites will be assessed immediately after irradiation and 24 hours post irradiation (Wednesday) and duplicate patches will be re-applied as applied on Monday. Same procedure will be repeated on Thursday as done on Tuesday and on Friday the patch sites will be evaluated. The same process will continue for 3 consecutive weeks. Then there will be 2 weeks of Rest phase; where there will be no product or patch applications. Rest phase is further followed by Challenge phase at week 6 (Visit 19 to Visit 23) where there will be a duplicate parallel series of product applications under semi-occlusive patches to 2 naïve areas on Monday. Post 24 hours (Tuesday) patches will be removed and 1 of the 2 sites will be irradiated similar as done in induction phase. The sites will be assessed immediately post irradiation and after 24 hours (Tuesday), 48 hours (Wednesday) and 72 hours (Thursday) of irradiation. At visit 23, after the challenge phase the final assessments will be performed by the dermatologist.

Official Title
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A Photo-irritation and Photo-sensitisation Study in Healthy Subjects for Three Developmental Cosmetic Facial Products

Conditions
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Skin Care

Intervention / Treatment
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* Other: Serum
* Other: Lotion
* Other: Cream
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant provision of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed. A participant who is willing and able to comply with scheduled visits, treatment plan, and other study procedures. A participant in good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant or relevant abnormalities in medical history or upon dermal examination, or condition, that would impact the participant's safety, wellbeing or the outcome of the study, if they were to participate in the study, or affect the individual's ability to understand and follow study procedures and requirements. A participant with Fitzpatrick phototype II to IV. A participant with healthy, intact skin at the proposed test area dorsum (below the shoulder, above the waist), as evaluated by a dermatologist, to ensure participant is free of clinically relevant dermatological conditions. Exclusion Criteria: A participant who is an employee of the investigational site, either directly involved in the conduct of the study or a member of their immediate family; or an employee of the investigational site otherwise supervised by the investigator; or, a GSK CH employee directly involved in the conduct of the study or a member of their immediate family. A participant who has participated in other studies involving investigational product(s) within 30 Days prior to study entry and/or during study participation. A participant who has participated in other studies including non-medicinal, cosmetic studies within 7 Days prior to study entry and/or during study participation. A participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or medically qualified designee, would make the participant inappropriate for entry into this study. A participant who is pregnant (self-reported). A participant who is breastfeeding. A participant with known or suspected intolerance or hypersensitivity to the study materials/product (or closely related compounds) or any of their stated ingredients, to hypoallergenic tape, or to the cotton patches. A participant who, in the opinion of the investigator or medically qualified designee, should not participate in the study. A participant unwilling or unable to comply with the Lifestyle Considerations; a) applying other product to test site, using cosmetics, b) changing dietary habits, c) getting patch test site wet, d) removing the patch, e) wearing tight or restrictive clothing that can remove patch, f) engaging in activities that result in excessive sweating, and g) intentional exposure to artificial ultraviolet light or cosmetic procedures. A participant with current or recent (within last 6 months before the start of the study) history of atopic lesions and/or eczema, psoriasis or skin cancer. A participant with a history of allergic reactions to topical-use products, cosmetics or medications or their ingredients. A participant with any history of significant diseases or medical conditions known to alter skin appearance or physiologic response (e.g. diabetes) which could, in the opinion of the Investigator, preclude topical application of the investigational products and/or interfere with the evaluation of the test site reaction. A participant considered immune-compromised. A participant with active dermatosis (local or disseminated) that might interfere with the results of the study. A Participant with history of diseases aggravated or triggered by ultraviolet radiation. A participant currently using any medication, which in the opinion of the investigator, may affect the evaluation of the investigational product, or place the participant at undue risk (e.g. any photosensitising medication such as tetracycline, thiazides, fluoroquinolones, etc.) within one month prior to inclusion. A participant who has used any of the following topical or systemic medications up to two weeks before the screening visit: immuno-suppressants, antihistamines, nonsteroidal anti-inflammatory drugs (NSAIDS), and particular aspirin (>200mg/d), within two weeks prior to inclusion and/or corticosteroids. A participant who has used oral or topical treatment with vitamin A acid and/or its derivatives up to 1 month before the screening visit. A participant who has been vaccinated up to 1 month before the screening visit or is intending to receive a vaccination during their participation in the study. Currently receiving allergy injections or received an allergy injection within 7 days prior to Visit 1 or expects to begin injections during study participation. A participant with any skin marks on the back that might interfere with the evaluation of possible skin reactions (e.g. pigmentation disorders, vascular malformations, scars, tattoos, excessive hair, numerous freckles, open sores, pimples, or cysts). A participant that intends bathing (in the sea or a pool), using a sauna, or partaking in water sports, or activities that lead to intense sweating for the duration of the study. A participant who has used a transcutaneous electrical nerve stimulation (TENS) machine 1 day before the screening visit or intends to use a TENS machine at any point during the study. A participant with history of sensitisation in a previous patch study. A participant with history of abnormal reaction to sun exposure. A participant who had intense sunlight exposure or sun tanning sessions up to 30 days before the screening evaluation. A participant with recent history (within the last 5 years) of alcohol or other substance abuse. A participant who has previously been enrolled in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Developmental Serum<br>All participants in induction phase will be topically applied 2 semi-occlusive patch (Monday) containing developmental serum (0.02milliliters per centimeter square[mL/cm^2] in an individual cell of patch) at 2 sites on the dorsum for 24 hours, post patch removal(Tuesday), sites will be cleaned, developmental serum will be re-applied and 1 of the 2 sites will be irradiated with 2.5 Joules per centimeters square(J/cm^2) ultraviolet(UV) A radiation,then with 0.3 minimal erythemal doses(MEDs) of UVA+UVB radiation. 24 hours post irradiation (Wednesday), sites will be assessed and duplicate patches applied as on Monday for 24 hours. Irradiation on Thursday similar to Tuesday and assessment post 24 hour irradiation on Friday. Same process repeated for 3 weeks. In challenge phase all participants will be applied 2 semi-occlusive patches at 2 naive sites for 24 hours, post which 1 site will be irradiated (same as induction phase). Assessment will be after 24, 48 and 72 hours of irradiation | Other: Serum<br>* Participants will be topically applied adhesive patch containing developmental serum<br>|
| Experimental: Developmental Lotion<br>All participants in induction phase will be topically applied 2 semi-occlusive patch (Monday) containing developmental lotion (0.02mL/cm^2 in an individual cell of patch) at 2 sites on the dorsum for 24 hours, post patch removal(Tuesday), sites will be cleaned, developmental lotion will be re-applied and 1 of the 2 sites will be irradiated with 2.5J/cm^2 UVA radiation, then with 0.3 MEDs of UVA+UVB radiation. 24 hours post irradiation (Wednesday), sites will be assessed and duplicate patches applied as on Monday for 24 hours. Irradiation on Thursday similar to Tuesday and assessment post 24 hour irradiation on Friday. Same process repeated for 3 weeks. In challenge phase all participants will be applied 2 semi-occlusive patches at 2 naive sites for 24 hours, post which 1 site will be irradiated (same as induction phase). Assessment will be after 24, 48 and 72 hours of irradiation | Other: Lotion<br>* Participants will be topically applied adhesive patch containing developmental lotion<br>|
| Experimental: Developmental Cream<br>All participants in induction phase will be topically applied 2 semi-occlusive patch (Monday) containing developmental cream (0.02mL/cm^2 in an individual cell of patch) at 2 sites on the dorsum for 24 hours, post patch removal(Tuesday), sites will be cleaned, developmental cream will be re-applied and 1 of the 2 sites will be irradiated with 2.5J/cm^2 UVA radiation, then with 0.3 MEDs of UVA+UVB radiation. 24 hours post irradiation (Wednesday), sites will be assessed and duplicate patches applied as on Monday for 24 hours. Irradiation on Thursday similar to Tuesday and assessment post 24 hour irradiation on Friday. Same process repeated for 3 weeks. In challenge phase all participants will be applied 2 semi-occlusive patches at 2 naive sites for 24 hours, post which 1 site will be irradiated (same as induction phase). Assessment will be after 24, 48 and 72 hours of irradiation | Other: Cream<br>* Participants will be topically applied adhesive patch containing developmental cream<br>|
| Placebo Comparator: Negative Control<br>All participants in induction phase will be topically applied 2 semi-occlusive patch (Monday) containing 0.9 percent normal saline (0.02mL/cm^2 in an individual cell of patch) at 2 sites on the dorsum for 24 hours, post patch removal(Tuesday), sites will be cleaned, normal saline will be re-applied and 1 of the 2 sites will be irradiated with 2.5J/cm^2 UVA radiation, then with 0.3 MEDs of UVA+UVB radiation. 24 hours post irradiation (Wednesday), sites will be assessed and duplicate patches applied as on Monday for 24 hours. Irradiation on Thursday similar to Tuesday and assessment post 24 hour irradiation on Friday. Same process repeated for 3 weeks. In challenge phase all participants will be applied 2 semi-occlusive patches at 2 naive sites for 24 hours, post which 1 site will be irradiated (same as induction phase). Assessment will be after 24, 48 and 72 hours of irradiation | Other: Normal Saline<br>* Participants will be topically applied adhesive patch containing normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Photo-initiated Potential Sensitization Reaction | Scoring of patch test reactions was performed by blind evaluator as per International Contact Dermatitis Research Group (ICDRG) grading '- to +++',where '-':negative reaction;'?+':doubtful reaction(faint erythema only),'+':weak(non-vesicular) positive reaction(erythema, infiltration and possibly papules);'++':strong(vesicular) positive reaction (erythema,infiltration,papules,vesicles); '+++':extreme positive reaction (bullous reaction, intense erythema and infiltration, coalescing vesicles).Score range '- to +++' where '-' indicated no adverse reaction and '+++' indicated very strong adverse reaction.Any positive reaction ('+' or greater):considered potential sensitization(PS) upon dermatologist discretion and as potential photo-initiated if a)positive reaction occur at ultraviolet (UV) exposed site,b)occur at both UV and non-UV sites with maximum score at UV exposed site being higher than non-UV exposed site.Percentage of participants with photo-initiated PS were reported in numbers. | Day 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Photo-initiated Reaction (Score of '+' or Greater) Which is Not Considered Potential Sensitization Reaction | Scoring of patch test reactions was performed by blind evaluator as per ICDRG grading '- to +++', where '-':negative reaction; '?+':doubtful reaction(faint erythema only),'+':weak(non-vesicular) positive reaction(erythema, infiltration and possibly papules);'++':strong(vesicular) positive reaction (erythema, infiltration, papules, vesicles);'+++':extreme positive reaction (bullous reaction, intense erythema and infiltration, coalescing vesicles).Score range '- to +++' where '-' indicated no adverse reaction and '+++' indicated very strong adverse reaction.Any positive reaction ('+' or greater) was classified as photo-initiated if a) a positive reaction occurs only at UV exposed site,b) occur at both UV and non-UV site with maximum score at UV exposed site being higher than maximum score at non-UV exposed site. Percentage of participants with any photo-initiated reaction (score of '+' or greater) without potential sensitisation were reported in form of numbers. | Day 40 | 
| Percentage of Participants With a Potential Sensitization Reaction Which is Not Considered Photo-initiated | Scoring of patch test reactions was performed by blind evaluator as per ICDRG grading grading '- to +++', where '-':negative reaction; '?+':doubtful reaction(faint erythema only),'+':weak(non-vesicular) positive reaction(erythema, infiltration and possibly papules); '++':strong(vesicular) positive reaction (erythema, infiltration, papules and vesicles); '+++':extreme positive reaction (bullous reaction, intense erythema and infiltration, coalescing vesicles). Score range '- to +++' where '-' indicates no adverse reaction and '+++' indicates very strong adverse reaction.Any positive reaction (a score of '+' or greater) was considered as potential sensitization based upon dermatologist discretion and was further considered as non-photoinitiated if: a positive reaction occurs only at the non-UV exposed site. Percentage of participants with any non-photoinitiated potential sensitisation was reported in form of numbers. | Day 40 | 
| Percentage of Participants With a Non-photoinitiated Reaction (Score of '+' or Greater) Which is Not Considered Potential Sensitization Reaction | Scoring of patch test reactions was performed by blind evaluator as per ICDRG grading grading '- to +++', where '-':negative reaction; '?+':doubtful reaction(faint erythema only),'+':weak(non-vesicular) positive reaction(erythema, infiltration and possibly papules); '++':strong(vesicular) positive reaction (erythema, infiltration, papules and vesicles); '+++':extreme positive reaction (bullous reaction, intense erythema and infiltration, coalescing vesicles). Score range '- to +++' where '-' indicates no adverse reaction and '+++' indicates very strong adverse reaction.Any positive reaction (a score of '+' or greater) was considered as non-photoinitiated if: a positive reaction occurs only at the non-UV exposed site. Percentage of participants with non-photoinitiated reaction (score of '+' or greater) without potential sensitization was reported in form of numbers. | Day 40 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin Care, Cosmetic Facial Product