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

Efficacy and Safety of a Combined Topical Formula (Azelaic Acid and Tranexamic Acid) Versus Placebo in Patients With Melasma: Randomized, Double-blind, Controlled Clinical Trial.

The goal of this clinical trial is to learn whether a topical formulation containing 12% azelaic acid and 5% tranexamic acid is effective and safe for treating melasma in adults. The main questions it aims to answer are:

Does the topical formulation reduce melasma severity compared with placebo after 4 weeks of treatment? Is the topical formulation safe and well tolerated?

Researchers will compare the active topical formulation with a placebo cream to determine whether the active treatment provides greater improvement in melasma severity and quality of life.

Participants will:

Be randomly assigned to receive either the active topical formulation or a placebo cream.

Apply the assigned treatment daily for 4 weeks. Attend scheduled clinical visits for assessment of melasma severity using the Melasma Area and Severity Index (MASI), quality of life using the Melasma Quality of Life Scale (MelasQoL), and standardized facial imaging with the VISIA® skin analysis system.

Be monitored for local adverse events throughout the study.

Study Overview

• Status: Completed
• Conditions: Melasma
• Intervention / Treatment: Drug: Topical azelaic acid 12% plus tranexamic acid 5%; Drug: Placebo topical formulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Estado de Baja California
    • Tijuana, Estado de Baja California, Mexico, 22010
      • The Skin Place

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Azelaic Acid + Tranexamic Acid; Participants received a topical formulation containing 12% azelaic acid and 5% tranexamic acid. The formulation was applied according to the study protocol for 4 weeks.	Drug: Topical azelaic acid 12% plus tranexamic acid 5%; 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 Comparator: Placebo Comparator; Participants received a placebo topical formulation identical in appearance and packaging to the investigational product. The placebo was applied according to the study protocol for 4 weeks.	Drug: Placebo topical formulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Melasma Area and Severity Index (MASI) score	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.	Baseline and Week 4

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Guadalajara

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2026
• Primary Completion (Actual): July 10, 2026
• Study Completion (Actual): July 13, 2026

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Placebo-controlled; Melasma; Tranexamic acid; Hyperpigmentation; Azelaic acid
• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Skin and Connective Tissue Diseases; Melanosis; Hyperpigmentation; azelaic acid
• Other Study ID Numbers: CUCS Protocol 26-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because no data-sharing plan was established for this investigator-initiated study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No