Tretinoin gel microspheres 0.04% versus 0.1% in adolescents and adults with mild to moderate acne vulgaris: a 12-week, multicenter, randomized, double-blind, parallel-group, phase IV trial.

BACKGROUND: Topical retinoids are considered first-line therapy in the treatment of acne vulgaris, yet can be associated with cutaneous irritation, including erythema, peeling, dryness, burning, and itching. Tretinoin gel microsphere (TGM) formulations were developed to minimize these effects. A lower-strength TGM formulation may be desirable to further reduce exposure to tretinoin.
OBJECTIVE: This study was conducted to assess the efficacy and safety profile of a lower-dose TGM (0.04%) formulation compared with TGM 0.1% for the treatment of mild to moderate acne vulgaris.
METHODS: In this multicenter, double-blind, parallel-group, Phase IV dose-ranging study, patients with facial acne were randomized to apply either TGM 0.04% or TGM 0.1% to the face each night for 12 weeks. Patients must have discontinued systemic retinoid treatment for at least 1 year before the study and were not to have used any topical retinoids, systemic antibiotics, nicotinamide, or systemic steroids for at least 1 month. All other topical medications applied to the face (including corticosteroids, antimicrobials, salicylic acid, and benzoyl peroxide) were to be discontinued at least 2 weeks before the study. End points were the acne lesion count (total, inflammatory, and noninflammatory lesions) and the investigators' and patients' assessments of improvement. Adverse events (including severity and relationship to treatment) and signs and symptoms of cutaneous irritation at the treatment site were monitored at each study visit.
RESULTS: One hundred fifty-six patients (78 TGM 0.04%, 78 TGM 0.1%) were randomized and received treatment. Patients ranged in age from 12 to 41 years (mean, 18.4 years) and were predominantly white (n = 89 [57.1%]) and male (n = 80 [51.3%]). Both TGM 0.04% and TGM 0.1% were associated with a reduction from baseline in total, inflammatory, and noninflammatory lesions. The differences between groups in the change in lesion counts from baseline to weeks 2, 4, 8, and 12 were not statistically significant. However, there was a greater reduction in inflammatory lesions at week 2 for TGM 0.1% compared with TGM 0.04% (14.8% vs 6.0%, respectively; P < 0.047). Both treatment groups had similar improvements in the investigators' global evaluation and the patients' assessment of the response to treatment. Both TGM 0.04% and TGM 0.1% were well tolerated. The most common adverse events were skin-associated burning sensation (2.6% in the TGM 0.04% group and 7.7% in the TGM 0.1% group) and irritation (6.4% and 3.8%, respectively). In the TGM 0.04% group, significantly fewer patients experienced dryness of the treatment area during the early phase of treatment (P < 0.027). However, for other measures of cutaneous irritation (peeling, burning/stinging, and itching), either there were no statistically significant differences between treatment groups or, in the case of erythema, there was a significant difference in favor of TGM 0.1% (P = 0.035).
CONCLUSIONS: Both TGM 0.04% and TGM 0.1% were associated with reductions in lesion counts in these patients with mild to moderate facial acne. Both concentrations were generally well tolerated. The results suggested an early (week 2) incremental benefit for the use of TGM 0.1% in the treatment of inflammatory lesions.

RCT Entities:   Population Interventions Outcomes