PRISM Study-Pruritus Relief Through Itch Scratch Modulation

Inclusion Criteria:

• Individuals diagnosed with generalized nodular PN, covering 2 separate body parts, and 10 or more pruriginous nodules
• Severe itch due to PN
• Age 18 years and older at the time of consent, and a life expectancy of at least 18months.
• Individuals using antidepressants must be on a stable dose for a minimum of 4 weeksprior to screening.

Exclusion Criteria:

• Pruritus due to localized PN (only one body part affected), or less than 10 nodules
• Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopicdermatitis or bullous pemphigoid for example).
• Unresolved acute secondary dermatoses active (unresolved) in the last (a) 4 weeks:localized contact dermatitis, environmental exposures, superficial burns, or viralexanthems; (b) 8 weeks: skin or environmental infestations, such as scabies, lice, orbed bugs.
• Other non-dermatologic diseases that could be a potential cause of concomitantpruritus (e.g., thyroid disease, celiac disease, hepatitis C virus [HCV]) must eitherhave resolved, been successfully treated (i.e., HCV RNA negative) or must besuccessfully managed with stable, optimized treatment (e.g., thyroid replacement,dietary management with resolution of symptoms, respectively) for at least 3 monthsprior to screening
• History of a major psychiatric disorder such as bipolar disorder or schizophrenia.History of active substance abuse in the last 3 years.
• Known intolerance (GI, CNS symptoms) or hypersensitivity/drug allergy to opioids.
• Use of certain concomitant medications and treatments within a period prior to thestudy, or requirement for these medications during the study:
• Potential subjects taking opiates, gabapentin, pregabalin, calcineurininhibitors, cannabinoid agonists, capsaicin, cryosurgery, topical doxepin,thalidomide or methotrexate, topical antihistamines or topical corticosteroidsrequire a 14-day washout.
• Within 4 weeks prior to screening: ultraviolet (UV)-therapy, exposure to anyinvestigational medication, including placebo
• Within 3 months prior to screening: Non-insulin biologics (including monoclonalantibodies) that modify the immune system,
• Individuals taking monoamine oxidase inhibitors are excluded, as concomitantopiate use may increase the risk for serotonin syndrome.
• Myocardial infarction or acute coronary syndrome within the previous 3 months, asreported by the subject.
• Individuals with prolonged QTcF Individuals with HIV can be included if they meet the following criteria: (a) currently ona stable (> 6 months stable use) and well tolerated highly active antiretroviral therapyregimen; (b) CD4 count > 500 cells/mL; and (c) HIV ribonucleic acid (RNA) < 50 copies/mLdocumented for at least 6 months prior to enrollment.