|The following article is part of The Clinical Advisor’s coverage from the 2018 American Association of Nurse Practitioners’ annual meeting in Denver. Our staff will be reporting live on original research, case studies, and professional outreach and advocacy news from leading NPs in various therapeutic areas. Check back for ongoing updates from AANP 2018.|
NKTR-181 has potential as a less abuse-prone substitute for conventional Schedule II opioids. In a poster presentation at the American Association of Nurse Practitioners 2018 National Conference, the new full mu-opioid receptor agonist analgesic was reported to exhibit “significantly less abuse potential compared with oxycodone.”
A double-blind, double-dummy, crossover study enrolled healthy subjects between the ages of 18 and 55 with no prior history of opioid dependency. These adults did, however, each report recreational opioid use on at least 10 occasions within a year prior to the start of the study and at least once within 12 weeks of study screening. Participants were randomly assigned to NKTR-181 in supratherapeutic doses of 400, 600, and 1200 mg; oxycodone 40 and 60 mg; and placebo. These tests were done with the intention of generating a mean Drug Liking rating for NKTR-181 compared with oxycodone.
Among the 54 subjects who completed the treatment, the least-squares (LS) mean maximum effect for Drug Liking was 62.0, 67.9, and 76.7 for NKTR-181 400, 600, and 1200 mg, respectively, v 76.6 and 81.5 for oxycodone 40 and 60 mg, respectively, and 53.2 for placebo (P <.0001 for NKTR-181 400 and 600 mg vs all oxycodone doses; P =.0071 for NKTR-181 1200 mg vs oxycodone 60 mg). Similar trends were observed for Drug High and Take Drug Again. Additionally, Drug Liking scores increased significantly more rapidly for both oxycodone doses than for any of the NKTR-181 doses. The LS mean rate of increase for Drug Liking for the first 2 hours was significantly lower for NKTR-181 than oxycodone at all dose level comparisons (P =.0032 for NKTR-181 1200 mg vs oxycodone 40 mg; P <.0001 of all other comparisons).
In a previous human abuse potential (HAP) trial, NKTR-181 was associated with lower Drug High and Drug Liking values vs oxycodone in recreational opioid users. The results of the study presented at this year’s conference are based on much higher doses of NKTR-181 than were used in the previous HAP trial.
In the recently completed SUMMIT-07 study (ClinicalTrials.gov Identifier: NCT023672), subjects treated with NKTR-181 100 to 400 mg were found to have achieved a significant reduction in pain compared with subjects treated with placebo. This human abuse study of recreational opioid users also found NKTR-181 to have significantly less potential for abuse compared with oxycodone.
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Ge X, Lu L, Jobes J, et al. Abuse potential of NKTR-181 in recreational opioid users: result from a randomized, double-blind crossover oral study. Presented at the American Association of Nurse Practitioners 2018 National Conference. June 26-July 1, 2018. Denver, CO. Industry Scientific Poster 10.