Human Abuse Potential of Oral NKTR-181 in Recreational Opioid Users: A Randomized, Double-Blind, Crossover Study

Author:

Ge Xue1,Henningfield Jack E23,Siddhanti Suresh1,Jobes Janet1,Lu Lin1,Xie Sunny1,Ziola Margaret1,Kelsh Debra4,Vince Bradley4,Di Fonzo Carlo J1,Tagliaferri Mary1,Zalevsky Jonathan1,Doberstein Stephen K1,Hoch Ute1,Eldon Michael A1

Affiliation:

1. Nektar Therapeutics, San Francisco, California

2. The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, Maryland

3. Pinney Associates, Bethesda, Maryland

4. Altasciences Clinical Research, Overland Park, Kansas, USA

Abstract

Abstract Objective To evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of oral NKTR-181 (oxycodegol), a novel full mu-opioid receptor agonist, relative to oral oxycodone. Design This double-blind, randomized, single-dose, crossover human abuse potential study was conducted in healthy, adult, non–physically dependent recreational opioid users. Setting Inpatient clinical research site. Subjects Seventy-one subjects randomized (95.7% male, 65.2% African American, mean age = 31.7 years). Methods The primary objective was to compare two therapeutic doses of NKTR-181 (400 and 600 mg) with 40 and 60 mg of oxycodone and a supratherapeutic dose (1200 mg) of NKTR-181 with 60 mg of oxycodone using visual analog scale (VAS) ratings for Drug Liking “at this moment” (Drug Liking). Secondary objectives included VAS ratings for other subjective measures, and central nervous system (CNS) mu-opioid effects were assessed using pupillometry. Each subject received single oral doses of five treatments and matching placebo. Results Compared with 40 and 60 mg of oxycodone, the maximum mean Drug Liking score at 400 and 600 mg NKTR-181 was significantly lower, and the rate of onset and extent of Drug Liking for all NKTR-181 doses in the first two hours postdose were also significantly lower. Delayed attenuated Drug Liking and pupillary miosis response following administration of NKTR-181 vs oxycodone were consistent with slower NKTR-181 CNS entry kinetics and mu-opioid receptor binding. No adverse events were rated as severe, and somnolence and dizziness occurred more frequently when subjects received oxycodone. Conclusions NKTR-181 at oral doses of 400 and 600 mg showed significantly fewer and less severe subjective effects accepted as representative of opioid abuse potential, such as lower peak Drug Liking in recreational opioid users, than 40 and 60 mg of oxycodone.

Funder

Nektar Therapeutics

Publisher

Oxford University Press (OUP)

Subject

Anesthesiology and Pain Medicine,Neurology (clinical),General Medicine

Reference57 articles.

1. Chronic opioid therapy for chronic non-cancer pain: A review and comparison of treatment guidelines;Cheung;Pain Physician,2014

2. Opioids for low back pain;Deyo;BMJ,2015

3. Assessing the prevalence of opioid misuse, abuse, and addiction in chronic pain;Ballantyne;Pain,2015

4. The effectiveness and risks of long-term opioid therapy for chronic pain: A systematic review for a National Institutes of Health Pathways to Prevention Workshop;Chou;Ann Intern Med,2015

5. Trends in opioid analgesic abuse and mortality in the United States;Dart;N Engl J Med,2015

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