Background Derma-Smoothe/FS ® (Fluocinolone acetonide ) Contains 0.01% fluocinolone acetonide in an oil base solution, Categorized as a low to medium potency

HiLL Dermaceuticals, Inc.

Speciality Dermatologicals for Children & Adults

Background

Derma-Smoothe/FS® (Fluocinolone acetonide ) Contains 0.01% fluocinolone acetonide in an oil base solution, Categorized as a low to medium potency corticosteroid

preparation.

Two independent open-label safety studies were conducted to assess the adrenal (HPA axis) suppression potential of Derma-Smoothe/FS®, in children 2 to 12 years of age, with moderate to severe atopic dermatitis.

Derma-Smoothe/FS® was approved for pediatric indication based on these safety studies and well-controlled clinical efficacy studies.



Study Design

Multi-center, open-label safety studies for the treatment of atopic dermatitis (eczema)

Patient criteria: Moderate to severe atopic dermatitis involving greater than 50% of the total body surface area (BSA)

Dosage and duration of treatment: Twice daily application on diseased skin; continuous treatment for 4 weeks

Criteria for (Safety) evaluation: Cosyntropin (ACTH) stimulation test Serum Cortisol levels, baseline and post stimulation



Study Design (continued)

Day 1 prior to first treatment, and at Day 29 after last treatment: Pre-stimulation serum Cortisol level (baseline)

assessment Immediately followed by stimulation with Cosyntropin

test (intravenous) Post-stimulation serum Cortisol level (after 60 minutes)

Data was compared using the paired t-test



Discussion of Results

ITT population 34 subjects 18 applied drug on > 75% BSA 16 applied drug on 50-75% of BSA

Approximate drug used per day: 9.5 + 4.7 mL/day

Baseline Cortisol levels did not change from Day 1 to Day 29 (Study 1, p=0.622) (Study 2, p=0.376)

Increase in Cortisol levels after stimulation was not significantly different from Day 1 to Day 29 (Study 1, p=0.296) (Study 2, p=0.647)



Solomon JR: Pediatric burns. Crit Care Clin 1:159-174, 1985



Cortisol Concentration at Baseline

11.5 + 3.9 11.2 + 2.7 0.622

Increase in Cortisol After Stimulation

15.4 + 7.8 14.0 + 4.1 0.296

At Start of Study(N=21)

After 4 Weeks of Treatment

(N=21)

Week 0 vs. Week 4p = value*

*Pooled data for 4 centers

Study 1



Cortisol Concentration at Baseline

10.73 + 5.01 9.35 + 3.82 0.376

Increase in Cortisol After Stimulation

15.39 + 4.81 14.85 + 3.10 0.647

At Start of Study(N=13)

After 4 Weeks of Treatment

(N=13)

Week 0 vs. Week 4p = value*

*p-value from paired t-test

Study 2

Reference range for Cortisol values : 3.4 – 26.9 µg/dL

ACTH stimulation test criterion for normal response at 60 minutes: approximate doubling of the basal plasma cortisol value



Example of drug exposure estimation

4 fl oz bottle of Derma-Smoothe/FS® contains 12mg of fluocinolone acetonide (FA) Ave. daily dose of 9.5mL of Derma-Smoothe/FS® ~ 1mg of FA Note: 1-2% corticosteroid is absorbed topically Based on a 1-2% absorption, the total FA absorbed is

0.02mg/dayReference: (H.I Maibach, Ch. Surber, Topical Corticosteroids, 1992; 165, 199, 201

Comparative quantitative studies utilized in the FDA diseased-skin protocol demonstrate that as little as 14 g/week of clobetasol propionate may induce suppression, and over 49 g/week of betamethasone dipropionate is required to significantly reduce plasma cortisol levels.



Conclusion

Four weeks twice daily application of Derma-Smoothe/FS® (fluocinolone acetonide 0.01%) to diseased skin involving over 50 to 90% of body surface area --

no change in morning baseline value of plasma Cortisol, nor did it affect Cortisol stimulation by administration of ACTH.



Efficacy results after 4 weeks treatment showed excellent or better (75% to 100%) improvement in more than 60% of the subjects.

Documents

Background Derma-Smoothe/FS ® (Fluocinolone acetonide ) Contains 0.01% fluocinolone acetonide in an oil base solution, Categorized as a low to medium potency