Oral Human Abuse Potential of Oxycodone DETERx^® (Xtampza^® ER)

Abstract

Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate‐release oxycodone.

The Comparative Pharmacokinetics of Physical Manipulation by Crushing of Xtampza ® ER Compared with OxyContin ®

“…After crushing, OxyContin was bioequivalent to crushed oxycodone IR and was not bioequivalent to intact OxyContin. These results were similar to previously published data on the comparative PK of Xtampza ER and OxyContin administered intact and after crushing and chewing [8,13], confirming the results from a similar previously published study [10] and establishing the consistency of the PK of Xtampza ER (Supplementary Table), further demonstrating the ability of Xtampza ER to retain its ER characteristics after manipulation, unlike OxyContin [8,10,13,14]. Similar to previously published data [10], the safety profiles of crushed and intact Xtampza ER were comparable.…”

“…Studies with Xtampza ER indicate that it retains its ER characteristics after crushing or chewing [8,10]; as a result, Xtampza ER is the first and only ER opioid formulation that does not include language in the boxed warning about potential dangers of crushing or chewing before ingestion [26]. Based on published data [8,10,13,14], including this study, crushed OxyContin results in a rapid increase in serum oxycodone concentrations and thus, a higher AQ. This fact may reveal why oral abuse after manipulation remains prevalent for hard-to-crush tablet formulations.…”

“…Subjective, drug liking assessments are considered to be the most sensitive measures of abuse potential. However, results from a previous study have demonstrated a lower abuse potential for both chewed and intact Xtampza ER after oral administration compared with crushed oxycodone IR [13]. Another limitation of the study was crushing the products under controlled laboratory conditions.…”

“…Our study fulfills category 2 criteria, demonstrating that crushing Xtampza ER has little to no effect on the PK profile. Combining these data with that of previous studies [8][9][10]13], Xtampza ER has labeling [26] that includes data from all of the FDA-recommended categories. Data from in vitro studies have demonstrated that the formulation is difficult to prepare for injection [9].…”

“…Data from in vitro studies have demonstrated that the formulation is difficult to prepare for injection [9]. Data from the combination of in vitro and in vivo studies have shown that it is difficult to reduce the particle size of Xtampza ER microspheres [8], the ER characteristics are maintained after manipulation [10], and that Xtampza ER has lower drug liking after chewing [29] and after intranasal administration [30] when compared with IR oxycodone.…”