Efficacy and Tolerability of an Isobutylamido-thiazolyl-resorcinol Cream 0.2% for Facial Hyperpigmentation

Study Overview
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Brief Summary
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Facial hyperpigmentation is a common skin issue that can cause embarrassment and affect the quality of life in majority of people. The investigators are conducting a research to study an efficacy and tolerability of Isobutylamido-thiazolyl-resorcinol 0.2% in lightening of the facial hyperpigmentation in comparison to vehicle intervention in 4, 8 and 12-week period. The ultimate goal is to provide the best cosmetic cream to improve the quality of life of people who suffer from facial hyperpigmentation.

Detailed Description
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Facial hyperpigmentation is a skin issue that occurs frequently in people with darker skin types. Studies show that the prevalence of facial hyperpigmentation is related to ethnicity and is accounted for up to 40%of the total population. The pathogenesis of facial hyperpigmentation is still unclear, but several factors seem to contribute such as ultraviolet radiation, female hormones, and genetics, which increase melanin production in the skin cells, specifically the epidermal melanocyte, and dermal melanophage. Hyperpigmentation can be embarrassing and affect the quality of life in the pertained individuals. Tyrosinase enzyme plays a key element in melanin production which causes dark areas. In 2018, several studies have reported a new cosmetic product using Isobutylamido-thiazolyl-resorcinol (Beiersdorf AG, Hamburg, Germany) in facial hyperpigmentation. In vitro studies found that in melanocyte culture, Isobutylamido-thiazolyl-resorcinol inhibit melanin production. Studies discovered that Isobutylamido-thiazolyl-resorcinol 0.2% can reduce facial hyperpigmentation within 4 weeks. Hyperpigmentation begin to fade away within 12 weeks of daily application. The objective is to study efficacy and tolerability of a cosmetic formulation with Isobutylamido-thiazolyl-resorcinol 0.2% compared to its vehicle in facial hyperpigmentation after 4, 8 and 12-week. This is a randomized double-blind and vehicle-controlled study. Two hundred subjects both male and female 18 years or older with facial hyperpigmentation are recruited in the study. The study was performed at the Institute of Dermatology, Bangkok, Thailand. Subjects agree to attend monthly sessions every 4 weeks for 12 weeks.

Official Title
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Efficacy and Tolerability of an Isobutylamido-thiazolyl-resorcinol Cream 0.2% for Facial Hyperpigmentation, A Randomized Double-blind and Vehicle-Controlled Study

Conditions
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Facial Hyperpigmentation

Intervention / Treatment
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* Other: Isobutylamido-thiazolyl-resorcinol Cream 0.2%
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are Thai adults age 18 years old and above . Subjects suffer from facial hyperpigmentation for at least 10 years, with or without freckles, lentigo or dark sports. Subjects must be able to attend monthly sessions in the period of 12 weeks session. Subjects must refrain from using other whitening cream such as hydroquinone, azelaic acid, kojic acid, arbutin, glycolic acid or any other creams which whiten the skin including chemical peel or whitening pills such as Tranexamic acid at least 1 month before the trial. Subjects must refrain from receiving both ablative and nonablative laser treatment at least 3 months before the trial. Subjects who can apply sun screen with UVA and UVB protection that has a minimum of SPF30 daily. Exclusion Criteria: Subjects who have conditions such as Lichen planus pigmentosus, Pigmented contact dermatitis, Photosensitivity, Ashy dermatosis, Dermal melanosis, e.g. Nevus of Hori, Nevus of Ota, Dermal melanocyte hamartoma Subjects with a congenital disease which darkens skin tone, e.g. Addison's disease, Cushing's syndrome and Thyrotoxicosis Subjects with a congenital or serious disease with unpredictable symptoms such as Cirrhosis, cardiovascular diseases, Neurological diseases, gastrointestinal disease, Reproductive system diseases, Cancer and Psychiatric diseases. Subjects who take pills that might cause hyperpigmentation such as chemotherapy, Amiodarone, Chlorpromazine, Hydroxychloroquine, Gold, Birth control pills (if related to causing hyperpigmentation issue) Female subjects with pregnancy and breastfeeding. Subjects who are allergic to chemical compound in the cream such as Alcohol denat, Phenoxyethanol or fragrance.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, vehicle controlled, double-blind study and is performed at the Institute of Dermatology. Subjects are randomized into 2 groups by a computer prior to the start of the study - group 1 receives Isobutylamido-thiazolyl-resorcinol 0.2% cream and group 2 receives vehicle cream for 12 weeks. Both Study products have to be applied twice daily.Total of 4 clinical sessions are carried out in order to evaluate Isobutylamido-thiazolyl-resorcinol 0.2% efficacy and tolerability at week 4, 8 and 12. Subjects and investigators are blinded about allocation. The appearance of the vehicle formulation was similar to the verum formulation and could not be distinguished neither by patients nor by the investigator.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isobutylamido-thiazolyl-resorcinol Cream 0.2%<br>The cream contains 0.2% Isobutylamido-thiazolyl-resorcinol. | Other: Isobutylamido-thiazolyl-resorcinol Cream 0.2%<br>* Each bottle contains Isobutylamido-thiazolyl-resorcinol cream 0.2% to be applied on the entire face twice daily for 12 weeks.<br>|
| Placebo Comparator: Vehicle<br>The cream contains no active ingredients. | Other: Vehicle<br>* Each bottle contains vehicle cream to be applied on the entire face twice daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Color assessment of facial hyperpigmentation by Color Analysis program will be evaluated every visit. | Each visit, photos are taken on all patients by VISIA-CR system camera on 3 positions of the face, straight and 37* on both sides with standard unfiltered and cross polarized lens. Each time the photos are filed and the colors are analyzed in order to be compared the changes between visits. | 12 weeks | 
| Physician's Global Assessment of facial hyperpigmentation will be evaluated every visit. | Evaluate the changes of facial hyperpigmentation by global assessment score: 0=Completely clear,1=Almost clear, 2=Marked improved, 3=Moderate improved, 4=Slight improved, 5=No change, 6=Worse | 12 weeks | 
| Patient's Global Assessment of facial hyperpigmentation will be evaluated every visit. | Evaluate the changes of facial hyperpigmentation by global assessment score: 0=Completely clear,1=Almost clear, 2=Marked improved, 3=Moderate improved, 4=Slight improved, 5=No change, 6=Worse | 12 weeks | 
| Patient's Self-Grading of facial hyperpigmentation will be evaluated every visit. | Visual self-grading by patients from 1 to 10 by 1 is the least and 10 is the most in the criteria of evenness, spots and skin clarity | 12 weeks | 
| Evaluate side effects of Isobutylamido-thiazolyl-resorcinol cream 0.2% or vehicle cream every visit. | All patients are asked about the side effects of using the cream such as eczema, hypopigmentation, and redness. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isobutylamido-thiazolyl-resorcinol