Poster Number-44 - Cross-sectional Study of Tampering in an Abuse-Deterrent Formulation of an Extended-Release Opioid in a Treatment Center Population

Purpose: Opioid use disorders continue to plague many individuals even as misuse and abuse of prescription opioids has decreased [1]. Though prescription opioid abuse in general remains high among those with opioid use disorder (OUD) [2], abuse of immediate-release (IR) and extended release (ER) formulations does not occur equally. Among individuals with OUD, use of IR formulations was preferred over ER formulations, where ease of manipulation was cited as a chief reason for preferring the IR products [3]. Though IR formulations have had higher rates of abuse, ER formulations have historically been physically tampered with and used via unintended methods (e.g., chewing, smoking, snorting, or injecting) [4]. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release opioids. These formulations are designed to reduce a person’s ability to easily tamper with a drug, and they present a barrier against the person using in a manner not intended by the drug manufacturer, which has been shown to dissuade some individuals from transitioning from oral use to non-oral use [4]. While all ER oxycodone drugs now utilize ADFs to reduce tampering, there is still information to be gathered about their real-world utility [5]. The chemical formulation for XTAMPZA ER’s ADF is oxycodone myristate, which keeps its extended-release properties even with tampering to the drug. To test the effectiveness of oxycodone myristate, its rate of tampering in a treatment center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone.

Methods:

Methods: This cross-sectional study utilized data from the Treatment Center Programs Combined, which are included in the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System. The RADARS® System is a mosaic of programs that collect and report on trends in drug use throughout the US [6]. These data were collected between the third quarter of 2018 and the third quarter of 2021 from individuals upon entry into opioid treatment programs, and it included basic demographic data as well as drug history. The 163 treatment centers participating in the study are nationally distributed throughout 46 states and the District of Columbia. Both privately funded clinics and publicly funded opioid treatment programs participate. Surveys are self-administered and anonymous. Participants are asked about which drug products they used “to get high” in the past month and the route they used. For the purposes of these analyses, tampering was defined as chewing, smoking, snorting, or injecting an opioid. They were able to select as many opioids and routes of use as necessary. As a result, participants could have used more than one drug group during the study period. The analyses for this study investigated the relationship between oxycodone myristate tampering and three comparators: 1) IR SE oxycodone, 2) other ER oxycodone, and 3) ER oxymorphone. IR SE oxycodone was selected because IR formulations are more frequently prescribed than ER formulations [1], making them generally more available for abuse than ER formulations. No IR oxycodone formulation currently has abuse-deterrent labelling. Other ER oxycodone was selected because all current formulations are labelled as abuse-deterrent, presenting a contrast to a similar drug. Finally, ER oxymorphone was selected because it has high abuse potential via manipulation and manipulation has produced adverse health events historically. Logistic regression was used to estimate odds of manipulating oxycodone myristate compared to each drug comparator.

Results:

Results: The participants in this study were 57.6% male and predominantly white (78.4%). The mean age was 36.7 (SD=9.9). Of the 2,273 participants, 35.2% had previously overdosed on an opioid, and 33.9% had never previously been in a substance abuse treatment program. Health care professionals made up 5.6% of the sample, and 3.1% were former active-duty armed forces personnel. The highest percent of manipulation was seen in IR SE oxycodone (72.5%, 95% CI: 69.9, 74.9). ER oxymorphone had the next highest rate at 66.7% (95% CI: 62.1, 71.2), followed by ER oxycodone with 56.4% (95% CI: 53.9, 58.8) and oxycodone myristate with the lowest manipulation rate at 38.5% (95% CI: 23.4, 55.4). Overlap among the categories of drug manipulation was high. Only 16 individuals (< 1%) tampered with oxycodone myristate alone, while 1,066 individuals (42%) tampered with ER oxycodone alone. Those that tampered with both IR SE oxycodone and other ER oxycodone made up 14% (N=357) of the sample. Logistic regression analyses found that oxycodone myristate had lower odds of manipulation when compared to both IR SE oxycodone (OR=0.23 [0.11, 0.50], p=0.0002) and ER oxymorphone (OR=0.30 [0.14, 0.67], p=0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR=0.5 [0.24, 1.03], p=0.0612). These findings did not change when the estimates were adjusted for age and gender.

Conclusion:

Conclusion: The results of this study provide community-based, real-world evidence of the abuse deterrence of the oxycodone myristate formulation. These findings demonstrate that, in a sample of individuals entering a treatment program, oxycodone myristate is less likely to be manipulated than IR SE oxycodone and ER oxymorphone but was statistically no different than other abuse-deterrent oxycodone drugs. As seen by Severtson et al. [7], the reduction in tampering seen in this study may also extend to other real-world settings, such as those abusing, but not seeking treatment. These findings also provide additional post-market evidence of the real-world utility of ADF opioids [8, 9]. Though the estimated odds ratio was notable, no significant difference was observed between the two types of abuse-deterrent oxycodone products.  This suggests that individual abuse-deterrent technologies could result in different reductions in abuse, but, due to the rarity of manipulation of oxycodone myristate, this study was insufficiently powered to detect smaller effects. This finding highlights a need to evaluate each individual ADF technology separately. Disseminating information and research into ADF technology and outcomes, particularly among clinicians managing chronic pain, would add to the range of options clinicians have to combat misuse, abuse, and opioid use disorder.

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