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.

• Asimadoline (Drug), also known as No brand name, serial number and code name: kappa-opioid receptor agonist
• Placebo (Drug), also known as No brand name, serial number and code name: placebo-matched control

Primary outcomes

• Number of participants with adverse events [Participants will be followed for the duration of the study, an expected 12 weeks]

Secondary outcomes

• Change from Baseline in Worst Itching Severity using a Visual Analog Scale [4 weeks]
• Maximum observed plasma drug concentration (Cmax) [0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing]
• Time to reach Cmax in plasma (Tmax) [0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing]
• Area under the plasma concentration-versus-time curve (AUC) from the time of the dose to the end of the 12-hour dosing interval [0.5, 0.75, 1, 1.5, 2, 3, 5, 6 and 8 hours after dosing]

Sex: All, ages: 18 Years to any

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.

• Dawn McGuire, MD FAAN, Study director, Tioga Pharmaceuticals, Inc.