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

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Webster L, Henningfield J, Buchhalter AR, Siddhanti S, Lu L, Odinecs A, Di Fonzo CJ, Eldon MA

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

Pain Med. 2018 Feb 1;19(2):307-318. doi: 10.1093/pm/pnw344.

PubMed ID

28340145 [ View in PubMed

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Abstract

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 < 0.0001). Drug Liking scores for oxycodone increased rapidly within 15 minutes and peaked at approximately one hour postdose, whereas Drug Liking (and most secondary abuse potential measures) for all doses of NKTR-181 were comparable with placebo for at least the first hour. Only the 400 mg Drug Liking scores were minimally differentiated vs placebo from one and a half to four hours, but remained significantly lower than oxycodone (P < 0.003). NKTR-181 treatment-related adverse effects were mild and occurred at a lower rate compared with oxycodone. Conclusions: NKTR-181 demonstrated delayed onset of CNS effects and significantly lower abuse potential scores compared with oxycodone in recreational opioid users.

DrugBank Data that Cites this Article

Drugs

Loxicodegol

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Loxicodegol	P-glycoprotein 1	Protein	Humans	Unknown	Not Available	Details