PRISM Study-Pruritus Relief Through Itch Scratch Modulation

A Phase 2b/3, Randomized, Double-Blind, Placebo-Controlled, 2-Arm, Efficacy and Safety Study in Prurigo Nodularis (PN) With Nalbuphine ER Tablets for Pruritus Relief Through Itch Scratch Modulation (PRISM Study)

To investigate the anti-pruritic efficacy and safety of Nalbuphine Extended Release (ER) (NAL ER) tablets in Prurigo Nodularis. Participants were randomized to NAL ER (or matching placebo) with the primary endpoint evaluation at Week 14. During the open label extension, participants who received NAL ER were continued on NAL ER and participants who received placebo would then shift to NALER.

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 18 months.
• Individuals using antidepressants must be on a stable dose for a minimum of 4 weeks prior to screening.
• Participants with a history of acute secondary dermatoses within the preceding 6 months may enroll only if the dermatosis has resolved completely as follows per medical history or participant self-report and current clinical assessment: (a) Localized contact dermatitis, environmental exposures, superficial burns, or viral exanthems must have been resolved for at least 4 weeks prior to screening. (b) Skin or environmental infestations, such as scabies, lice, or bed bugs, must have been resolved for at least 8 weeks prior to screening.
• Any identified systemic, non-dermatologic disease that could be a potential cause of concomitant pruritus (e.g., thyroid disease, celiac disease, hepatitis C virus [HCV]) must either have resolved, been successfully treated [i.e., HCV ribonucleic acid (RNA) negative], or must be successfully managed with stable, optimized treatment (e.g., thyroid replacement, dietary management with resolution of symptoms, respectively) for at least 3 months prior to screening.
• Participants who are human immunodeficiency virus (HIV) positive may enroll if they meet the following criteria: (a) currently on a stable (> 6 months stable use) and well tolerated highly active antiretroviral therapy regimen; (b) cluster of differentiation 4 (CD4) count > 500 cells/mL; and (c) HIV ribonucleic acid (RNA) < 50 copies/mL documented for at least 6 months prior to enrollment.

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 atopic dermatitis or bullous pemphigoid for example).

• History of a major psychiatric disorder such as bipolar disorder or schizophrenia. History of active substance abuse in the last 3 years.

• Known intolerance [gastrointestinal (GI), central nervous system (CNS) symptoms] or hypersensitivity/drug allergy to opioids.

• Use of certain concomitant medications and treatments within a period prior to the study, or requirement for these medications during the study:

  • Potential participants taking opiates, gabapentin, pregabalin, calcineurin inhibitors, cannabinoid agonists, capsaicin, cryosurgery, topical doxepin, thalidomide or methotrexate, topical antihistamines or topical corticosteroids require a 14-day washout.
  • Within 4 weeks prior to screening: ultraviolet (UV)-therapy, exposure to any investigational medication, including placebo
  • Within 3 months prior to screening: Non-insulin biologics (including monoclonal antibodies) that modify the immune system,
  • Individuals taking monoamine oxidase inhibitors are excluded, as concomitant opiate use may increase the risk for serotonin syndrome.

• Myocardial infarction or acute coronary syndrome within the previous 3 months, as reported by the participant.

• Individuals with prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF).

Note: Other Inclusion/Exclusion criteria may apply.