A Novel Cream Formulation Containing Nicotinamide 4%, Arbutin 3%, Bisabolol 1%, and Retinaldehyde 0.05% for Treatment of Epidermal Melasma

Figure 2. Mean surface area of melasma measured at baseline (1398.5 mm2), day 30 (1116.9 mm2), and day 60 (923.4 mm2), showing a mean total reduction of 475.1 mm2 from baseline to day 60.

Figure 3. Clinical (A) and cross-polarized (B) photographs of a patient after 60 days of treatment with the novel compound containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05%.

In vivo RCM analyses at each time point showed reduction in pigmentation in the 4 levels of the skin that were evaluated, but the results were not statistically significant.

Participant satisfaction

There was strong statistical evidence of patient satisfaction with the treatment results at the end of the study period (P<.0001). At baseline, 75.8% (25/33) of participants were dissatisfied with the appearance of their skin as compared with 15.2% (5/33) at day 60. Additionally, 18.1% (6/33) and 6.1% (2/33) of the participants were satisfied and completely satisfied at baseline compared with 33.3% (11/33) and 51.5% (17/33) at day 60, respectively. Participant satisfaction with signs of facial aging also increased over the study period (P=.0104). At baseline, 60.6% (20/33) were dissatisfied, 12.1% (4/33) were satisfied, and 27.3% (9/33) were completely satisfied; at the end of treatment, 30.3% (10/33) were dissatisfied, 36.4% (12/33) were satisfied, and 33.3% (11/33) were completely satisfied with the improvement in signs of facial aging.

Increased patient satisfaction with facial skin texture at baseline compared to day 60 also was statistically significant (P=.0157). At baseline, 39.4% (13/33) of the participants were dissatisfied, 30.3% (10/33) were satisfied, and 30.3% (10/33) were completely satisfied with facial texture; at day 60, 15.1% (5/33) were dissatisfied, 30.3% (10/33) were satisfied, and 54.6% (18/33) were completely satisfied. Significant improvement from baseline to day 60 also was observed in participant assessment of skin oiliness (P=.0210), brightness (P=.0003), overall appearance (P<.0001), and hydration (P<.0001).

Product appreciation

At day 60, 89.7% (26/29) of the participants who completed the study rated the product’s ease of application as being at least “good,” with more than half of participants (55.2% [16/29]) rating it as “very good” or “excellent.” Overall satisfaction with the product was rated as “very good” or “excellent” by 48.3% (14/29) of the participants. Similar results were observed in participant assessments of consistency, smell, and absorption (Figure 4).

Figure 4. Participant responses to product appreciation questionnaire.

Safety evaluation

A total of 52 AEs were observed in 23 (69.7%) participants, which were recorded by participants in diary entries throughout treatment and evaluated by investigators at each time point. Among these AEs, 48 (92.3%) were considered possibly, probably, or conditionally related to treatment by the investigators based on clinical observation. The most common presumed treatment-related AE was a burning sensation on the skin, reported by 30.3% (10/33) of the participants at day 30 and 13.8% (4/29) at day 60. Of the reported AEs related to treatment, 91.7% (44/48) were of mild intensity and 93.8% (45/48) required no treatment or other action. There were no reported serious AEs related to the investigational product. Blood pressure, heart rate, and weight remained stable among all participants throughout the study.

The intensity of the AEs was described as “light” in 91.7% (44/48) of cases and “moderate” in 8.3% (4/48) of cases. The frequency of AEs was classified as “unique,” “intermittent,” or “continuous” in 45.8% (22/48), 39.6% (19/48), and14.6% (7/48) of cases, respectively. Of the 48 AEs, 3 (6.3%) occurred in 1 participant, necessitating interruption of treatment, application of the topical corticosteroid cream mometasone, and removal from the study.

Comment

Following treatment with the study cream containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and RAL 0.05%, the mean reduction in MASI score (P<.0001) and the mean reduction in total melasma surface area from baseline to end of treatment were statistically significant (P<.0001). The study product was associated with strong statistical evidence of patient satisfaction (P<.0001) regarding improvement in facial skin texture, skin oiliness, brightness, overall appearance, and hydration. Participants also responded favorably to the product and considered it safe and effective. In vivo RCM analysis demonstrated a reduction in the amount of melanin in 4 levels of the skin (superficial dermis, suprabasal layer/dermoepidermal junction, spinous layer, superficial granular layer) following treatment with the study cream; however, over the course of the 60-day treatment period, it did not reveal statistically significant reductions. This finding likely is due to the large ranges used to classify the amount of melanin present in each layer of the skin. These limitations suggest that scales used in future in vivo RCM analyses of melasma should be narrower.