A nasal abuse potential randomized clinical trial of REMOXY® ER, a high-viscosity extended-release oxycodone formulation

Nadav Friedmann, PhD, MD; Michael R. Marsman, PharmD; Annelies W. de Kater, PhD; Lindsay H. Burns, PhD; Lynn R. Webster, MD

doi:10.5055/jom.2018.0476

Authors

Nadav Friedmann, PhD, MD
Michael R. Marsman, PharmD
Annelies W. de Kater, PhD
Lindsay H. Burns, PhD
Lynn R. Webster, MD

DOI:

https://doi.org/10.5055/jom.2018.0476

Keywords:

opioid abuse, clinical liking study, snorting, Abuse Quotient

Abstract

Objective: This study examined the nasal abuse deterrence of REMOXY ER, a novel high-viscosity extended-release oxycodone formulation.

Design: An Institutional Review Board-approved, single-center, randomized, double-blind, placebo, and active-controlled, four-way crossover study of intranasal REMOXY ER gel, manipulated or intact, and ground oxycodone immediate-release (IR). An open label extension examined pharmacokinetics of OxyContin® ER in the first 20 subjects.

Participants: Healthy, adult nondependent recreational opioid users with a history of intranasal abuse. Thirty-eight subjects enrolled; 36 completed.

Setting: A clinical research in-patient unit.

Interventions: Cross-over arms included nasal self-administration of the entire contents of REMOXY ER 40 mg capsules (manipulated or intact), ground oxycodone IR 40 mg tablets, and placebo. The open-label arm was ground OxyContin ER.

Main outcome measures: The primary endpoint was the maximum effect (Emax) of visual analog scale ratings of Drug Liking. Secondary endpoints included Take Drug Again (12 and 24 hours), Drug High Emax, area under effect curves through 12 hours, pupillometry, peak oxycodone concentrations (Cmax), time to maximum concentration (Tmax), and Abuse Quotient (Cmax/Tmax).

Results: Intranasal REMOXY ER (manipulated or intact) elicited lower Drug Liking and Drug High compared to ground oxycodone IR. Secondary endpoints also reflected reduced Abuse Potential. Intranasal REMOXY ER (manipulated or intact) led to fourfold lower Cmax, a 57 to 128 percent longer Tmax, a >10-fold lower Abuse Quotient and lower Take Drug Again scores compared to both OxyContin ER and oxycodone IR.

Conclusion: In this study, REMOXY ER demonstrated significantly lower nasal abuse potential compared to oxycodone IR or OxyContin ER.

Perspective: Abuse-deterrent drugs are intended to help fight opioid abuse. Yet the persistence of the opioid epidemic indicates that vast improvements in abuse-deterrent technology are needed. A new, high-viscosity, extended-release oxycodone formulation showed robust abuse-deterrence against the nasal route of abuse in an Food and Drug Administration-advised clinical trial in recreational opioid users.

Author Biographies

Nadav Friedmann, PhD, MD

Clinical Operations, Pain Therapeutics, Inc., Austin, Texas

Michael R. Marsman, PharmD

Regulatory Affairs, Pain Therapeutics, Inc., Austin, Texas

Annelies W. de Kater, PhD

Pharmacology and Toxicology, W/D Consulting, Scotts Valley, California

Lindsay H. Burns, PhD

Neuroscience, Pain Therapeutics, Inc., Austin, Texas

Lynn R. Webster, MD

Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah

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