Efficacy and Safety of a Combined Topical Formula Versus Placebo in Patients With Melasma

Melasma is a chronic acquired pigmentary disorder characterized by symmetrical facial hyperpigmentation that significantly affects patients' quality of life. Although several topical therapies are available, treatment responses are often variable and recurrence is common. Azelaic acid inhibits melanogenesis through tyrosinase inhibition, whereas tranexamic acid modulates inflammatory and vascular pathways involved in melasma pathogenesis. Their complementary mechanisms suggest that combined topical administration may provide greater therapeutic benefit than either approach alone.

This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of a topical formulation containing 12% azelaic acid and 5% tranexamic acid compared with placebo in adults with melasma. Participants are randomly assigned to receive either the active formulation or placebo and are followed for four weeks. Clinical efficacy is assessed using the Melasma Area and Severity Index (MASI), patient-reported quality of life using the Melasma Quality of Life Scale (MelasQoL), and standardized facial imaging with the VISIA® skin analysis system. Safety is evaluated through the monitoring and documentation of local adverse events throughout the study.

The findings of this study are expected to provide evidence regarding the clinical efficacy, safety, and tolerability of this combined topical formulation as a potential therapeutic option for the treatment of melasma.

• Topical azelaic acid 12% plus tranexamic acid 5% (Drug): Topical formulation containing 12% azelaic acid and 5% tranexamic acid administered for the treatment of melasma. Participants applied the assigned formulation according to the study protocol for 4 weeks.
• Placebo topical formulation (Drug): Matching placebo topical formulation identical in appearance, packaging, and administration schedule to the investigational product. Participants applied the placebo according to the study protocol for 4 weeks.

Primary outcomes

• Change in Melasma Area and Severity Index (MASI) score [Baseline and Week 4]: Change in the Melasma Area and Severity Index (MASI) from baseline to Week 4. MASI was assessed by the investigator to evaluate clinical severity of melasma.

Secondary outcomes

• Change in Melasma Quality of Life Scale (MELASQoL) score [Baseline and Week 4]: Change in patient-reported quality of life using the Melasma Quality of Life Scale (MELASQoL) from baseline to Week 4.
• Change in facial pigmentation assessed by VISIA® [Baseline and Week 4]: Objective assessment of facial pigmentation using standardized VISIA® digital imaging, including evaluation of pigmentation intensity and spot count.
• Incidence of treatment-related adverse events [Throughout the 4-week treatment period]: Frequency and severity of local adverse events, including erythema, pruritus, and burning sensations, recorded throughout the study.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults aged 18 to 60 years.
* Clinical diagnosis of facial melasma.
* Fitzpatrick skin phototypes II to V.
* Willing and able to comply with all study procedures and scheduled visits.
* Willing to use sunscreen throughout the study.
* Provided written informed consent.

Exclusion Criteria:

* Pregnancy or breastfeeding.
* Known hypersensitivity to azelaic acid, tranexamic acid, or any component of the study formulation.
* Use of topical or systemic treatment for melasma within the previous 3 months.
* Presence of facial skin diseases or active skin infections that could interfere with study assessments.
* Participation in another clinical trial during the study period.
* Any medical condition that, in the investigator's judgment, could interfere with study participation or evaluation of the outcomes.