plasmin inhibitor used to prevent fibrinolysis to reduce blood loss. It exerts its effect by reversibly blocking lysine bindingsites on plasminogen, thus inhibiting plasminogen activator (PA) from converting plasminogen to plasmin. While plasminogen also exists in human epidermal basal cells and cultured human keratinocytes are known to produce PA, there is basic rationale that TXA may affect keratinocyte functions and interactions. 8 The anti-plasmin activity of TXA is thought as being the main mechanism of its hyperpigmentary effect. In several studies, treatment with topical TXA (2-5%) was shown to be well tolerated, with no serious side effects reported.5,10In a 12-week, single-center, clinical study, a novel topical facial serum containing 3% tranexamic acid, 1% kojic acid, and 5%niacinamide, was evaluated for its effectiveness in treating mild to moderate melasma, PIH, and hyperpigmentation in Brazilianfemale subjects. Efficacy parameters included expert clinical grading, bioinstrumental measurement, self-assessment questionnaires,and subjective and objective cutaneous tolerability assessment. TXA’s mechanism of action was also assessed utilizing in vitro cultures of human epidermal melanocytes.
In vivo Clinical Study
The clinical study was conducted at a contract research organization (CRO) in São Paulo, Brazil from May to September 2017(Allergisa-SP, Brazil). Written informed consent was obtained from all study subjects prior to enrollment. The study was conductedin accordance to the guidelines outlined by the Ethical Principles for Medical Research Involving Human Subjects- Helsinki Declaration (1964) and its successive updates.16 The CRO adhered to the Good Clinical Practice (GCP) guidelines throughout the course of the study. An Independent Ethics Committee (IEC) (Investiga – Instituto de Pesquisas, registered by the National Research Ethics Commission (CONEP)) approved the study.
The formulation evaluated was a hydroglycolic topical facial serum (Discoloration Defense, SkinCeuticals Inc., New York, NY) containing the following ingredients: 3% tranexamic acid (TXA), 1% kojic acid, 5% niacinamide, and 5% hydroxyethylpiperazineethane sulfonic acid (HEPES).SubjectsFifty-five healthy Brazilian female subjects aged 27 to 60 years (mean age, 41 years) were enrolled in the 12-week clinicalstudy. Subjects were non-smokers with Fitzpatrick skin types I-IV. At least 50% of subjects had self-perceived sensitive skin.The inclusion criteria for the study included a clinical evaluation score by a dermatologist on a visual analog scale for mild tomoderate hyperpigmentation, skin texture roughness, and skin tone unevenness. A dermatologist identified mild to moderatePIH (according to a visual analog scale) in 36 of the 55 subjects, and mild to moderate melasma (according to a modified MASIscale) in 48 of the 55 subjects.
The topical serum was evenly applied across a cleansed face in the morning and evening. The serum’s first application was conducted at the CRO during the inclusion visit (Day 0). Following the inclusion visit, subjects applied the topical serum at home for 12 weeks (D1-D83). The subjects were also provided with a sunscreen (SPF 70), which was applied to the face in the morning and as needed throughout the day prior to sun exposure.
Evaluation Parameters and Methods
Assessment of Facial DyschromiaClinical scoring of melasma according to a modified MASI scale was conducted by a dermatologist at pre-treatment baseline and weeks 2, 4, 8, and 12 on 48 of the 55 subjects who were identified as having melasma. The modified MASI score was calculated by subjective assessment of two factors: area of involvement (A) and darkness (D), with the forehead (f), right malar region (rm), left malar region (lm), and chin (c), corresponding to 30%, 30%, 30%, and 10% of the total face, respectively. The modified MASI was scored as follows and the range of the total score was 0 to 24: mMASI = 0.3A(f)D(f) + 0.3A(lm)D(lm) + 0.3A(rm)D(rm) + 0.1A(c)D(c) Expert clinical grading evaluations were conducted at pretreatment baseline, weeks 2, 4, 8, and 12. Facial dyschromiaparameters were clinically graded on a modified Griffith’s 5-point scale, with half-point increments, where 0=none (best possible condition) and 4=severe (worst possible condition). Efficacy measures included visual evaluation and grading by a dermatologist under standard daylight assessing the following attributes: appearance of PIH, hyperpigmentation, and skin texture. Skin tone homogeneity was clinically graded on a 4-point scale, with half-point increments, where 0 =none (best possible condition) and 3=severe (worst possible condition).Tolerability AssessmentTolerability assessments were conducted at pre-treatment baseline, weeks 2, 4, 8, and 12. Tolerability parameters weregraded on a scale where 0=none; 1=mild; 2=moderate; and 3=severe. Clinically-graded objective irritation parameters includederythema, dryness, scaling, and edema. In addition, subjects self-assessed burning, stinging, itching, tightness, and tingling.BioinstrumentationStandardized digital photographs of subjects were taken at the