# Presentation: 881145

## Study Design and Efficacy Results for Tinea Pedis Clinical Trials

- Kathleen Fritsch, Ph.D.
- Division of Biometrics III, FDA

## Part I: Clinical Trial Design for Tinea Pedis Trials

## Trial Characteristics

*Trial Design*
- Randomized, double-blind, vehicle controlled, multicenter
*Indications*
- tinea pedis (athlete’s foot)
- evaluate “all-comers” or multiple sub-types
- interdigital tinea pedis (athlete’s foot between the toes)
- evaluate interdigital variant only

## Patient Populations

*Randomized & treated population*
- positive KOH
- clinical signs and symptoms
*Efficacy analysis population (MITT)*
- must also have positive baseline culture
- 	(cultures take up to 4 weeks—treatment may be completed before baseline culture results are known)
- only ~2/3 of randomized patients have positive baseline culture

## 3 Nested Efficacy EndpointsInvolving Mycological & Clinical Outcomes

## Efficacy Endpoints

*Negative Mycology*
- negative KOH & culture
*Effective Treatment **(Sometimes Primary)*
- negative KOH & culture + mild or no signs &  symptoms (typically at most mild erythema and scaling, but definition varies)
*Complete Cure **(Often Primary)*
- negative KOH & culture + no signs & symptoms
*	**Signs and symptoms*: at a minimum--erythema,  pruritus, scaling (may include others)

**Notes:**
Expand discussion of effective treatment

## Study Phases

*Treatment period*
- Typical treatment duration is 1-4 weeks
*Post-treatment follow-up*
- 	Primary timepoint for efficacy evaluation at least 2 weeks after completing treatment
- 5 to 8 weeks post-treatment for 1 week Tx
- 2 to 4 weeks post-treatment for 4 week Tx
- In both cases, primary timepoint is 6 to 9 weeks after starting treatment

## Why is efficacy assessed during post-treatment follow-up?

- epidermal turnover may take several weeks
- may not expect clearance of some signs until at least 6 weeks after start of treatment, even if fungus is eradicated
- →May be significant time lag (weeks or months) between end of treatment and assessment of cure

## Part II: Data Presentation

- Efficacy results from selected clinical trials

## Selected Drug Products

- Criteria for dataset selection:
- NDA reviews available (oldest from 1988)
- vehicle controlled trials
- The 9 products/formulations/regimens identified represent:
- 6 active ingredients
- 4 Rx and 5 OTC products/regimens
- 4 one-week and 5 four-week regimens
- 7 “interdigital tinea pedis” and 2 “tinea pedis”

**Notes:**
discuss how 9 products were selected (vehicle controlled trials, reviews available)

## Sample Sizes

| 1-Week Treatments |  | 4-Week Treatments |  |
| --- | --- | --- | --- |
| Product | N
Act / Veh | Product | N
Act / Veh |
| A* | 253 / 265 | E* | 93 / 92 |
| B* | 88 / 80 | F* | 202 / 195 |
| C   | 58 / 28 | G* | 129 / 138 |
| D | 131 / 152 | H |   47 / 44 |
|  |  | I | 105 / 108 |

- *Data from 2 studies

## CAUTION!

- Data do NOT represent head-to-head comparisons of products!
- Success rates are influenced by
- Patient populations (e.g. concomitant disease, baseline severity)
- Clinical study procedures (e.g. sample collection, timing)
- Endpoint definitions (e.g. assessment scales, evaluations)
- 	which can vary substantially from trial to trial

## Efficacy Outcomes (9 Drug Products)

- Negative Mycology
- Effective Treatment
- Complete Cure

## Negative Mycology(End of Treatment)

## Negative Mycology(Primary Timepoint – Week 6-9)

## Effective Treatment(End of Treatment)

## Effective Treatment(Primary Timepoint – Week 6-9)

**Effective Treatment****(Primary Timepoint – Week 6-9)**

## Complete Cure(End of Treatment)

## Complete Cure(Primary Timepoint – Week 6-9)

## Clearance of Signs and Symptoms over Time (2 Drug Products)

- Erythema
- Scaling
- Pruritus

## Erythema(Percent of Subjects Clear)

## Scaling(Percent of Subjects Clear)

## Pruritus(Percent of Subjects Clear)

## Summary of Efficacy Results

- May be a time lag of several weeks between end of treatment and clearance of signs and symptoms (particularly for 1-week products)
- Most subjects have some signs and symptoms remaining post-treatment
- Typical cure rates at primary post-treatment timepoint (Week 6-9) are
- Complete cure: 20%
- Effective Treatment: 50%
- Negative Mycology: 70%