Background

1
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.

2
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

3
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

4
Discussion of Results

• ITT population 34 subjects
• 18 applied drug on gt 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, p0.622) (Study 2,
  p0.376)
• Increase in Cortisol levels after stimulation was
  not significantly different from Day 1 to Day 29
  (Study 1, p0.296) (Study 2, p0.647)

5
Solomon JR Pediatric burns. Crit Care Clin
1159-174, 1985
6
After 4 Weeks of Treatment (N21)
Study 1
Week 0 vs. Week 4 p value
At Start of Study (N21)
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
Pooled data for 4 centers
7
After 4 Weeks of Treatment (N13)
Study 2
Week 0 vs. Week 4 p value
At Start of Study (N13)
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
p-value from paired t-test
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
8
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/day
• Reference (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.

9
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.

10

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