Multiple-Dose Pharmacokinetics and Potential for Adrenal Suppression Following Treatment With Halobetasol Spray in Patients With Atopic Dermatitis

This is an open-label, safety study designed to assess the multiple-dose pharmacokinetics and
potential for adrenal suppression following topical treatment with halobetasol propionate
0.05% spray applied twice-daily in adult patients with moderate to severe atopic dermatitis.
At least 40 eligible patients with atopic dermatitis that satisfy all eligibility criteria
will be enrolled into the study. Patients must be overall in good health and should have a
current diagnosis of moderate to severe atopic dermatitis with Investigator Global Assessment
(IGA) score of at least 3 or 4. Patients will be stratified by age with:

Cohort 1: At least 20 patients 18 years of age and older with ≥ 25% BSA affected.

Cohort 2: At least 20 patients 12-16 years and 11 months of age with ≥ 25% BSA affected.

Cohort 2 will initiate enrollment once all enrolled patients in Cohort 1 have completed the
study and a safety analysis has been reviewed by the Medical Monitor and approved by the
Novum Independent Institutional Review Board (NIIRB). Sites will not begin enrollment of
patients in Cohort 2 until the site is notified by email that the safety analysis for Cohort
1 has been reviewed and approved. Each cohort will be enrolled based on the availability of
patients. Each cohort will be reviewed for the potential of HPA axis suppression. The Medical
Monitor or NIIRB may discontinue the study at any time if safety concerns are found. If 6 or
more patients in Cohort 1 experience HPA axis suppression, then enrollment for Cohort 1 will
be stopped. Cohort 2 will not be initiated if 6 or more patients enrolled in Cohort 1
experience HPA axis suppression or 30% or more of the final enrolled number of patients in
Cohort 1 experience HPA axis suppression. If 6 or more patients in Cohort 2 experience HPA
axis suppression, then enrollment for Cohort 2 will be stopped. If the study is stopped at
any time, patients currently enrolled will be contacted via phone and instructed to
discontinue study product immediately. Patients will be instructed to return for their next
scheduled visit for cortisol response testing. Sites will follow up with patients and monitor
for HPA axis suppression. All patients will be followed until cortisol levels are normal, as
defined in study protocol. Patients enrolled in the study will apply the study product twice
daily onto the affected skin areas for 14 days (Days 1-14), according to provided
instructions. .Patients will be instructed not to rub over the affected area after
application of spray. Each patient is expected to receive 28 doses of study product. All
patients will attend the clinic for the following 8 scheduled visits. Patients will apply the
morning dose of the study product in the clinic at each clinic visit (and evening dose on Day
4) and at home during non-clinic visits. A phone call will be made approximately 14 days
after the patient has completed dosing to follow-up on any new adverse events that may have
occurred. All patients will have a cortisol response test performed at screening and on Day
17 (at least 48 hours after last dose of study product).

The safety profile of the test product will be evaluated by analysis of reported adverse
events.

Inclusion Criteria:

1. Males or non-pregnant, non-lactating females:

- Cohort 1: 18 years of age and older

- Cohort 2: 12-16 years and 11 months of age (Cohort 2 will not begin enrollment
until review and approval of safety information from Cohort 1.)

2. If female and of childbearing potential, prepared to abstain from sexual intercourse
or use a reliable method of contraception during the study (e.g., condom, IUD, oral,
transdermal or injected hormonal contraceptives). Female patients using hormonal
contraceptives should have been on the same product/dosing regimen for at least 28
days before baseline and should not change this regimen during the study.

3. Signed informed consent form that meets all criteria of current FDA regulations. For a
patient considered to be a minor in the state he/she lives and is enrolled, the parent
or legal guardian will be required to sign the consent form and the patient will sign
an IRB approved "assent to participate" form. Approved informed consent and assent
forms specific to each cohort will be required.

4. Patients with a definite clinical diagnosis of moderate to severe atopic dermatitis
with ≥ 25% BSA affected (excluding face, scalp, groin, axillae and other
intertriginous areas)

5. Investigator Global Assessment (IGA) score of 3 (Moderate) or 4 (Severe).

6. Patients in Cohort 2 must weigh a minimum of 26 kg.

7. Results from a cortisol response test that are considered normal and show no evidence
of any abnormal HPA function or adrenal response. Patients must fulfill all of the
following stipulations:

1. Basal (pre Cortrosyn™ injection) cortisol concentration ≥ 5 mcg/100 mL.

2. 30-minute post-injection cortisol level is at least 7 mcg/100 mL greater than the
basal level (≥ basal value + 7).

3. Post-stimulation level > 18 mcg/100 mL.

Exclusion Criteria:

1. Females who are pregnant, nursing, planning to become pregnant during the duration of
the study, or if of childbearing potential and sexually active and not prepared to use
appropriate contraceptive methods to avoid pregnancy.

2. Mild atopic dermatitis.

3. IGA score < 3.

4. Atopic dermatitis with a BSA involvement < 25%.

5. Results from a cortisol response test that show evidence of any abnormal HPA function
or adrenal response:

1. Basal (pre CortrosynTM injection) cortisol concentration < 5 mcg/100 mL.

2. 30 minute post-injection cortisol level is less than 7 mcg/100 mL greater than
the basal level (< basal value + 7).

3. Post-stimulation level ≤ 18 mcg/100 mL.

6. Recurrent or active cutaneous bacterial or viral infection in any treatment area at
baseline (i.e., clinically infected atopic dermatitis).

7. Patient has a history of atopic dermatitis that has been unresponsive to topical
corticosteroid therapy.

8. Any condition (i.e., sunburn, psoriasis etc.) that, in the Investigator's opinion, may
interfere with the clinical assessments of the signs and symptoms of atopic
dermatitis.

9. History of prolonged bleeding or a past diagnosis of bleeding disorders and/or history
of blood loss exceeding 450 mL (including blood donations) within 1 month before the
study.

10. Patient with poor peripheral venous access.

11. History of mastectomy or lymphatic insufficiency of the upper limb (patient is
eligible if blood can be taken from the arm opposite the site of surgery or
condition).

12. History of allergy or sensitivity to corticosteroids or history of any drug
hypersensitivity or intolerance that, in the opinion of the Investigator, would
compromise the safety of the patient or the results of the study.

13. Patient has a significant history or current evidence of chronic infectious disease,
system disorder, Netherton's Syndrome, uncontrolled diabetes, organ disorder or
insufficiency, immunosuppression (from medical treatment or disease) or other medical
condition that, in the Investigator's opinion, would place the study patient at undue
risk by participation in the study or as an unsuitable candidate for pharmacokinetic
blood sampling.

14. Patient is currently receiving or has received any radiation therapy or
anti-neoplastic agents within 3 months before baseline.

15. Use within 4 weeks before baseline of 1) oral or intravenous corticosteroids, 2)
UVA/UVB therapy, 3) PUVA (psoralen plus ultraviolet A therapy, 4) topical tacrolimus,
5) topical pimecrolimus, 6) systemic retinoids or 7) any other systemic atopic
dermatitis treatment.

16. Known history of hypothalamic-pituitary-adrenal axis impairment or any other
disturbance of the adrenal function (e.g., Cushing or Addison disease).

17. Use of tanning booths or nonprescription UV light source within 2 weeks before
baseline.

18. Use within 8 weeks before baseline of 1) immunomodulators or immunosuppressive
therapies or 2) interferon.

19. Use within 14 days before baseline of 1) systemic antibiotics, 2) calcipotriene or
other Vitamin D preparations, or 3) topical retinoids.

20. Patients who have used topical treatments, prescription or over the counter,
including:

1. Any topical atopic dermatitis therapeutic agents of any kind within the 2 weeks
before baseline.

2. Any topical corticosteroids within the 2 weeks before baseline.

3. Any antibacterial, medicated and/or astringent washes, soaps, pads or
moisturizers within 3 days before baseline.

4. High strength (20% or above) alpha-hydroxy acid or any kind of peel or other
procedures (e.g., laser hair removal) within 30 days before baseline.

5. Any topical products (i.e., sunscreens, lotions, creams), except for bland
emollient (moisturizer) within 24 hour before baseline.

6. Topical antibiotics in the treatment area within 7 days before baseline.

21. Patient has been treated within 6 months before baseline with any biological therapies
for atopic dermatitis.

22. Inability to understand the protocol requirements, instructions, and study-related
restrictions, the nature, scope, and possible consequences of the clinical study.

23. Unlikely to comply with the protocol requirements, instructions, and study-related
restrictions, such as uncooperative attitude, inability to return for follow-up
visits, and improbability of completing the clinical study.

24. Receipt of any drug as part of a research study within 30 days before baseline.

25. The patient is a member of the investigational study staff or a member of the family
of the investigational study staff.

26. Previous participation in this study.