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A double-blind, placebo-controlled dose-ranging study evaluated five dosing regimens of pramiconazole, an oral broad-spectrum triazole antifungal agent, for the treatment of pityriasis versicolor. Four treatment groups demonstrated significant efficacy compared with placebo.
"Pramiconazole is a new, promising antifungal that provides a short-term therapy solution for the treatment of tinea versicolor, and which is an improvement over the existing therapies," says Jan Faergemann, M.D., Ph.D., principal investigator for the clinical trial and professor of dermatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Pramiconazole is a broad-spectrum triazole antifungal agent being developed by Barrier Therapeutics. Results of a previous phase 2 trial involving 19 patients with pityriasis versicolor demonstrated the efficacy of treatment with pramiconazole 200 mg once daily for three days.
The dose-ranging study enrolled 147 adult patients with pityriasis versicolor, who were randomized into one of six treatment arms to receive placebo or once-daily treatment with pramiconazole 100 mg x 1 dose, 200 mg x one dose, 400 mg x one dose, 200 mg x two doses, or 200 mg x three doses.
To be eligible for participation, patients needed to have KOH microscopy confirmation of Malassezia spp, at least mild desquamation, and either multiple lesions involving at least two different anatomic body sites or skin involvement of at least 15 percent of body surface area.
Evaluations were performed at baseline, and then after 14 and 28 days, to assess mycological response, clinical signs and symptoms (desquamation, erythema, pigmentary changes, itching), and Investigators Global Assessment (IGA) based on erythema, itching and desquamation.
The comprehensive safety evaluations included clinical laboratory parameters, electrocardiogram, and a limited physical exam with vital signs.
Treatment success, defined by negative KOH microscopy plus either complete resolution of erythema, desquamation and pruritus or, in patients who presented with more moderate-to-severe disease, the presence of only minimal disease signs and symptoms, was analyzed as the primary efficacy endpoint.
The results showed a linear, dose-dependent response and statistically significant differences between placebo and all pramiconazole regimens, except for the lowest dose group.
Success rates in the placebo and pramiconazole 100 mg x one dose group were 16 percent and 34.5 percent, respectively, and ranged from 59.1 percent to 84.5 percent in the four other pramiconazole groups.
The outcomes analyses showed a similar pattern of results for the secondary efficacy endpoints of mycological cure and IGA.
At day 28, 16 percent of placebo-treated patients and 42.3 percent of patients in the pramiconazole 100 mg x one dose group had a negative KOH microscopy.
Successful mycological cure in the remaining four pramiconazole groups ranged from 68.2 percent to 96.2 percent.
Success rates based on the IGA were nearly identical to those for mycological cure.
About one-third of patients experienced an adverse event, and while most were considered treatment-related, they were generally mild in severity, and there were no serious adverse events judged as secondary to study treatment.
The incidence of individual adverse events was similar across all treatment groups and was less than 1.5 percent, with the exception of diarrhea (23.8 percent) and nausea (4.8 percent).
There were also no clinically important changes in any findings of the physical examination or laboratory testing.
Post-treatment ECG changes were noted in one patient treated with pramiconazole 100 mg x one dose (first-degree atrioventricular block) and one placebo patient (QTcF >450 ms).
"These results warrant further development of pramiconazole for this indication," Dr. Faergemann says.
Disclosure: Dr. Faergemann has no financial interest in Barrier Therapeutics or pramiconazole.