Effects of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl diglycinate/niacinamide topical emulsion in Thai adults with melasma: a single-center, randomized, double-blind, controlled study

Abstract

Background: Melasma is an acquired hyperpigmentary disorder characterized by dark patches or macules located on the cheeks, forehead, upper lip, chin, and neck. Treatment of melasma involves the use of topical hypopigmenting agents such as hydroquinone, tretinoin, and azelaic acid and its derivatives. Objective: The purpose of this study was to assess the efficacy of a formulation containing a combination of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl diglycinate/niacinamide compared with an emulsion-based control in the treatment of melasma in Thai adults. Methods: In this single-center, randomized, double-blind, controlled study, Thai patients with mild to moderate facial melasma (relative melanin value [RMV] in range of 20–120) were randomized for the application of either the test or the emulsion-based (control) product in the morning and before bedtime for 8 weeks. The supplemental sunscreen product with sun protection factor 30 was distributed to all patients. Subjects were assessed for the intensity of their hyperpigmented skin area by measuring the difference in the absolute melanin value between hyperpigmented skin and normal skin (RMV). This parameter was used as a primary outcome of this study. Additionally, the severity of melasma was determined visually using the Melasma Area and Severity Index (MASI) scored independently by 3 investigators. The assessments of melasma intensity and other skin properties were performed before administration (week 0) and every 2 weeks thereafter for up to 8 weeks. Other skin properties, including moisture content, pH, and redness (erythema value), were measured. Adverse events (AEs), including erythema, scaling, and edema, were also assessed by a dermatologist using the visual grading scale of Frosch and Kligman and COLIPA. Results: The resulting primary intent-to-treat (ITT) population included 33 patients in the test group and 34 patients in the control group. Sixty patients completed all 8 weeks of the study (on-treatment [OT] population): 91% (30) of the 33 patients in the test group, and 88% (30) of the 34 patients in the control group. Between-group differences in mean RMV were statistically significant at week 6 in both the primary ITT ( P = 0.005) and OT ( P = 0.006) populations. The significant differences in mean MASI scores between the test and the control groups were initially observed at weeks 4 ( P = 0.005) and 8 ( P = 0.027) in the OT and primary ITT populations, respectively. Other parameters, including skin pH, erythema, and moisture content did not significantly change from baseline at any time point of study. The incidence of AEs was not different between the test (4/33 [12%]) and control (5/34 [15%]) groups. Conclusions: The significant differences in RMVs between the test and control groups were observed after 6 weeks of treatment, both in the primary ITT and OT populations. The incidence of patients with AEs was not significantly different between the test and control groups.