Candida antifungal performs well in study

The double-blind, vehicle-controlled trial, conducted at 20 participating clinical sites in the United States and Latin America, included 236 children under the age of 3 with a culture-proven diagnosis of Candida diaper dermatitis. Patients were randomized 1:1 to treatment with the topical antifungal ointment or its vehicle to be applied at every diaper change for seven days.

The primary efficacy endpoint for the study was "overall cure" at day 14, defined as absence of all clinical signs of disease with eradication of the fungus. The proportion of patients achieving that outcome was twofold higher in the miconazole 0.25 percent ointment group compared with the controls (22 percent vs. 10 percent), and the difference between treatments was highly statistically significant (p=0.005).

The treatment was very well-tolerated. In addition, blood levels measured in previous studies showed that there is very low to no systemic absorption of the topically applied antifungal agent.

"Candida diaper dermatitis has been treated successfully for many years, but with the empiric use of products tested in adults. With this study, we uniquely have efficacy and safety data for a treatment formulated especially for use in infants and children and investigated in that population in a rigorous, well-designed clinical trial. With the approval of this miconazole ointment, we would finally have an antifungal product for the treatment of Candida diaper dermatitis that we could comfortably prescribe and recommend knowing there are solid data demonstrating its efficacy and safety," says Mary Spraker, M.D., pediatric dermatologist and associate professor, departments of dermatology and pediatrics, Emory University, Atlanta.

Dr. Spraker is a consultant to Barrier Therapeutics and assisted in designing the study protocol. In the phase 3 trial, all children randomized to treatment had specimens obtained for culture at baseline and on study days seven and 14. In addition, disease severity was evaluated at baseline and on days three, five, seven and 14 by rating the presence of erythema, papules/pustules and erosions.

The rate of complete clinical cure, defined as complete resolution of all of the clinical signs (a total severity score of 0), was about threefold higher in the miconazole-treated group compared with controls at both days seven and 14. The miconazole ointment also significantly outperformed its vehicle at days seven and 14 with respect to microbiological cure rates. At day 14, clinical cure was achieved in 38 percent of children treated with the miconazole ointment compared with 11 percent of controls (p<0.001); corresponding rates for microbiological cure were 50 percent and 23 percent, respectively (p<0.001).

"Overall cure and complete clinical cure are very stringent efficacy criteria, since it is not unusual for there to be some residual post-inflammatory changes, even when the fungus is eradicated. Therefore, it is important to also consider results from other analyses of severity scores as an efficacy measure for this Candida diaper dermatitis treatment," Dr. Spraker notes.

Analyses of improvement in disease severity scores showed a statistically significant difference favoring the miconazole ointment as early as day three. The difference between treatments increased progressively at later visits and remained statistically significant. At the end of the seven-day treatment period, the severity score was reduced by an average of 72 percent in children treated with the miconazole ointment compared with only 25 percent in those using the vehicle. By the last visit, nearly two-thirds of miconazole-treated patients were categorized as responders, defined as a patient with a symptom severity score of 0 or 1, compared with only about 20 percent of the controls.

Results from safety monitoring showed there were no serious adverse events in either treatment group or any adverse events judged to be treatment-related. Nonserious adverse events were evenly distributed between the groups and typical of what would be expected in the population studied.