Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Pruritus Associated With Atopic Dermatitis

Asimadoline has been administered to over 1900 human subjects or patients in clinical trials
and exhibits an acceptable safety profile. Due to its high selectivity for the kappa-opioid
receptor, asimadoline does not produce mu-opioid like side-effects. Results from preclinical
models indicate asimadoline significantly reduces the frequency of scratching induced by
pruritic agents. This double-blind placebo-controlled clinical study is designed to evaluate
the safety, tolerability and clinical efficacy of asimadoline in patients with pruritus
associated with atopic dermatitis.

Main Inclusion Criteria:

1. Signed informed consent and must be able and willing to follow study procedures and
instructions

2. Male or female subject aged 18 years or older (no upper age limit)

3. Established clinical diagnosis of atopic dermatitis for at least 6 months

4. Itching Visual Analog Scale (VAS) average worst itching score of at least 40 mm on a
100 mm scale

5. Female subject of childbearing potential and male subject of procreative capacity
agree to use an effective method of contraception for the duration of the study

Main Exclusion Criteria:

1. Pregnant, attempting to conceive, or nursing

2. Received phototherapy (ultraviolet B, psoralen plus ultraviolet A) within the previous
4 weeks

3. Received treatment with any of the following within the previous 2 weeks:

- Topical or oral immunosuppressants or calcineurin inhibitors, sedating
anti-histamines or anti-histamines taken for pruritus treatment, prescription topical
corticosteroid creams or ointments, any other oral or topical steroids, aprepitant,
naltrexone, pregabalin, gabapentin, or tricyclic antidepressants, or any other
medications that, in the investigator's judgement, could affect the subject's pruritus
or atopic dermatitis, and that are not specified below

OR taking any of the following and has not been on stable use for at least the
previous 4 weeks:

- Non-prescription topical hydrocortisone creams or ointments, lotions, moisturizers,
emollients, bath oil treatments, non-sedating oral anti-histamines being taken for
allergy treatment, selective serotonin reuptake inhibitor (SSRI) antidepressants.

4. Currently participating in other investigational clinical studies or having received
investigational drugs in a clinical research study within the previous 3 months.
Subjects currently enrolled in an observational study are eligible for participation
in this study, however subjects must not enroll in a new observational study during
the course of their participation in this study

5. Pruritus due to conditions other than atopic dermatitis (e.g., hepatitis, biliary
cirrhosis, scabies) or due to medications known to cause pruritus

6. Acute illnesses, uncontrolled or unmanaged diabetes or thyroid disease, decompensated
heart failure, cirrhosis or liver failure, chronic kidney disease, or uncontrolled
psychiatric disease

7. Evidence or treatment of malignancy (other than localized basal cell cancer, squamous
cell skin cancer, or cancer in situ that has been resected) within the previous 5
years

8. History of HIV infection

9. History of alcohol or drug abuse within the past 3 years

10. Diseases or conditions that could, in the opinion of the investigator, interfere with
the assessment of safety and efficacy of the study drug and compliance of the subject
with study visits/procedures (e.g. exacerbation of multiple sclerosis or other
comorbid conditions)

11. Use of any product that acts as an inhibitor of P-glycoprotein (P-gp) or as a P-gp
substrate (with the exception of topical ketoconazole product for skin or scalp)
within the previous 4 weeks

12. Known allergy to asimadoline or its drug components.