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.
• 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 is approved for pediatric use.

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 (cont.)

• Day 1 prior to first treatment application, and
  at the end of 4 weeks treatment
• Pre-stimulation serum Cortisol level (baseline)
• 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
Treatment applications

• 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

5
Solomon JR Pediatric burns. Crit Care Clin
1159-174, 1985
6
Cortisol Levels Prior to Treatment
Cortisol levels Prior to treatment
No. of patients (N34)
Pre-Stimulation Avg. Cortisol level 11.63
60 min. Post-Stimulation Avg. Cortisol level 26.82
ACTH stimulation test criterion for normal
response at 60 minutes approximate doubling of
the basal plasma cortisol value.
7
Cortisol levels after 4 weeks of Treatment
Cortisol levels end of 4 weeks Treatment.
No. of patients (N34)
Pre-Stimulation Avg. Cortisol level 11.26
60 min. Post-Stimulation Avg. Cortisol level 25.06
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

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