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J. Cosmet. Sci., 71, 263–290 (September/October 2020) 263 Evaluating the Safety and Effi cacy of a Topical Formulation Containing Epidermal Growth Factor, Tranexamic Acid, Vitamin C, Arbutin, Niacinamide and Other Ingredients as Hydroquinone 4% Alternatives to Improve Hyperpigmentation: A Prospective, Randomized, Controlled Split Face Study BRANDON D. KALASHO, ARDALAN MINOKADEH, SANDY ZHANG-NUNES, RICHARD A. ZOUMALAN, NIMA L. SHEMIRANI, ANDREA R. WALDMAN, VADIM PLETZER, and CHRISTOPHER I. ZOUMALAN , Zoumalan Plastic Surgery, Beverly Hills, CA (B.D.K., R.A.Z., C.I.Z.) , Skin Care and Laser Physicians of Beverly Hills, Los Angeles, CA (A.M.), Department of Ophthalmology, Keck School of Medicine of USC, Los Angeles, CA (S.Z.-N.), Eos Rejuvenation, Beverly Hills, CA(N.L.S.), Albert Einstein College of Medicine, Montefi ore Medical Center, New York , NY (A.R.W.), KlinConsult, Wellington, New Zealand (V.P.) Accepted for publication April 13, 2020 . Synopsis Hyperpigmentation is a common concern of patients in aesthetic practice. There are various treatment options, but topical depigmenting agents such as hydroquinone (HQ) are usually a fi rst-line option. Given HQ’s side effects and potential controversy over its long-term use from prior animal studies, there is a consumer demand for non-HQ topical formulations that provide similar effi cacy, but with a reduced adverse reaction profi le to HQ. There is increasing evidence to support the use of selective growth factors, tranexamic acid, niacinamide, arbutin, and Vitamin C in improving hyperpigmentation. This study sought to determine whether a non-HQ topical formulation, composed of the aforementioned ingredients, could provide similar or improved effi cacy to topical HQ, but with a reduced adverse reaction profi le. This single-center, prospective, randomized, controlled split face study investigated the safety and effi cacy of a proprietary product SKNB19 compared with hydroquinone 4% (HQ4%) in treating hyperpigmentation. Eighteen adult subjects with facial pigmentation were randomly assigned to have one side of their face treated with SKNB19 twice a day (morning and night application) and the other treated with HQ4% applied nightly. Patients used a 5-point scale to self-assess their overall appearance, and a 4-point scale to assess redness, irritation, and tolerability to the skin-brightening creams. A Wilcoxon signed-rank test was used to test whether there was a statistical Address all correspondence to Christopher I. Zoumalan at research@zoumalanmd.com.