Human Abuse Potential of the New Opioid Analgesic Molecule NKTR-181 Compared with Oxycodone

Objective Evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of NKTR-181, a novel mu-opioid agonist molecule, relative to oxycodone. Design This randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study enrolled healthy, adult, non–physically dependent recreational opioid users. Setting Inpatient clinical research site. Subjects Forty-two randomized subjects (73.8% male, 81% white, mean age = 25 years). Methods The primary objective was to evaluate single orally administered 100, 200, and 400 mg NKTR-181 doses in solution compared with 40 mg oxycodone and placebo solutions using the Drug Liking visual analog scale. Secondary measures included the Drug Effects Questionnaire, Addiction Research Center Inventory/Morphine Benzedrine Group Subscale, Price Value Assessment Questionnaire, Global Assessment of Overall Drug Liking, and Take Drug Again Assessment. Central nervous system mu-opioid effects were assessed using pupillometry. The study included qualifying and treatment phases. Subjects received each of the five treatments using a crossover design. Results NKTR-181 at all dose levels had significantly lower Drug Liking Emax than oxycodone (P