FOOD AND DRUG ADMINISTRATION
CENTER FOR DRUG EVALUATION AND RESEARCH (CDER)
Q
Joint Meeting of the
Non-Prescription Drugs and Dermatologic and Opthalmic
Drugs Advisory Committee
May 6-7, 2004
uestionsIssues for the Committee for NDAC/DODAC
May 6-7, 2004
Clinical Efficacy
1)FDA
presented information on the types of studies that have been conducted to
support NDAs for an indication of tinea pedis.
Most studies employed a
design where a single concentration and dose regimen were compared
to a vehicle control. The efficacy endpoints included complete cure[1],
effective treatment[2] and mycological
cure[3]. Recently, the primary endpoint in many trials has
been complete cure.
a.Please
discuss the merits of the current
endpoints and discuss which endpoint is most relevant to assessing the efficacy
of a product.
1) What,
if anyPlease comment on what, is the lowest acceptable rate of cure that is clinically
meaningful for a
topical OTC drug product for the treatment of tinea pedis, using complete clinical
and mycological clearance as definition of “cure”? Please discuss your rationale.
2) Dose response studies are not conducted in the
development programs of antifungal products for the treatment of tinea
pedis. Given the efficacy of products currently marketed, Sshould topical
antifungal drug development programs for tinea pedis evaluate safety and
efficacy at different concentrations, dosing durations, and dosing frequencies?
F
3) FDA has received numerous reports of lack of effect for topical
antifungal products. It is not clear if
this is a reflection on the actual efficacy of the products or a reflection of
consumer expectations regarding cure of tinea pedis.
a. Should
FDA consider adding information to labeling on the following:
i.
Cure rate (e.g. complete cure) or effective treatment
ii.
Expectation of symptom relief
iii.
Delay in response relative to the end of treatment
b. Are
there claims on the current labeling that may mislead consumers to have greater
expectations of benefit than are merited by the efficacy data available?
Clinical Microbiology
4)
Given the efficacy rates
observed in the clinical trials, should antifungal drug resistance be a
concern?
4)
Should antifungal minimum inhibitory concentrations, (MICs) be determined for
clinical isolates during drug development and submitted with the NDA?
5)
Safety
4)
Expectation
of symptom relief
4)
When to
discontinue drug use (especially in a setting where symptoms may persist beyond
the recommended duration of treatment)
4)
Please discuss your
view of whether the phrase “cures most” is informative and accurate in OTC
consumer labeling?
6)
Should
antifungal drug resistance be a concern given the cure rates observed
in the clinical trials? Is the risk of secondary infections (e.g.,
bacterial cellulitis), related to inadequately treated tinea pedis, of
sufficient frequency and severity as to merit communication in OTC consumer
labeling?
a. Are
there specific subpopulations at risk for secondary infections that should be identified on the
label?Should the
potential for resistance be crafted into OTC labeling?
Should antifungal MICs be determined for
clinical isolates during drug development and submitted with the NDA?
Is the risk of secondary infections (e.g.,
bacterial cellulitis), related to inadequately treated tinea pedis, of sufficient
frequency and severity as to merit communication in OTC consumer labeling? If so, what message should be crafted into
OTC labeling?