NDAC Will Evaluate Trial Design, Labeling For Athlete’s Foot OTCs

FDA's Nonprescription and Dermatologic & Ophthalmic Drugs advisory committees will discuss clinical trial design and future development programs for drugs treating interdigital Tinea pedis during their May 6-7 meeting in Rockville, MD.

In light of past studies in which products "have not been rigorously tested for identification of the dose and dosing regimen that can provide an optimal benefit-risk ratio," the agency is seeking committee guidance on clinical trial design. FDA's "ultimate goal is to provide products that maximize the likelihood of complete cure for the consumer."

Both Schering-Plough's Lotrimin Ultra (butenafine hydrochloride) and Novartis' Lamisil AT (terbenafine hydrochloride) carry the interdigital claim on their labels.

FDA convened the panel after receiving requests from sponsors regarding development of drug products with treatment durations of less than one week. Products currently on the market are available in both one- and four-week treatment periods.

Briefing documents for the meeting describe the studies received by the agency following the publication of the advance notice of proposed rulemaking for the OTC topical antifungal monograph in 1982. Ten of the submitted studies were identified as appropriately designed to demonstrate effectiveness of active ingredients.

FDA notes there was "considerable variability in the study protocols," including treatment duration and whether diagnosis of tinea pedis was determined by physician or a positive culture. The studies also used varying criteria for cure.

"All of these factors make it difficult to compare the cure rates of the monograph products to those of the NDA products because of differences in the design of the clinical studies," the document states.

Additionally, at the time, "the panel expressed concerns about the ingredients only mitigating the symptoms rather than curing the condition."

The committees also will address the possibility of new labeling for athlete's foot products already on the market.

A change in labeling may be required to clarify the time lapse that can occur between use of the product and cure of the condition. The agency says it has received reports from consumers saying available treatments do not work.

"Given the efficacy of this class of drugs and numerous consumer complaints on the lack of efficacy, it is apparent that consumers may not understand that people may not achieve symptom relief or cure by the end of the treatment," FDA notes.

Currently, products falling under the OTC topical antifungal monograph carry the labeling statement: "Stop use and ask a doctor if irritation occurs or if there is no improvement within 4 weeks."

However, labeling for OTCs approved under new drug applications can be less specific. One example of an OTC NDA label given by FDA reads: "Apply a thin layer over affected area twice a day for 4 weeks or as directed by a doctor. If condition persists longer, ask a doctor."

Therefore, FDA says, "in contrast to OTC monograph labeling, the warnings on OTC NDA products do not explicitly inform the consumers about the time of expected outcome."

"Further, consumers may not understand that they may not achieve a cure at all from the treatment" the document continues.

FDA will ask the committees to comment on whether information on the lag time between treatment and efficacy should be included in labeling. They will advise the agency on how the information should be provided, either on the carton or the package insert.

The briefing documents provide an example of Rogaine labeling that makes a similar clarification. "It takes time to regrow hair. Results may occur at 2 months with twice a day usage. For some men, you may need to use this product for at least 4 months before you see results," the label states.

Similarly, Prilosec OTC labeling reads: "not intended for immediate relief of heartburn: this drug may take 1 to 4 days for full effect."

Finally, the committees will address complications with untreated Tinea pedis and whether drug resistance should be a concern given the complete cure rates observed in the clinical trials.

FDA announced in March its plans to hold the meeting (¹ (Also see "OTC Athlete’s Foot Drugs Scheduled For FDA Advisory Committee Review" - Pink Sheet, 22 Mar, 2004.), p. 9).