Impact of physical manipulation on in vitro and in vivo release profiles of oxycodone DETERx®: An extended-release, abuse-deterrent formulation

Kopecky, Ernest A.; Fleming, Alison B.; Noonan, Patrick K.; Varanasi, Ravi K.; Grima, Michael; Saim, Said; Mayock, Stephen P.

doi:10.5055/jom.2014.0211

Cited by 27 publications

(24 citation statements)

References 12 publications

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“…1Photograph showing the spherical, microparticulate nature of oxycodone DETERx capsule contents. Republished with the permission of Weston Medical Publishing, LLC, from the article “Impact of physical manipulation on in vitro and in vivo release profiles of oxycodone DETERx: an extended-release, abuse-deterrent formulation” (Kopecky EA et al Journal of Opioid Management 2014;10(4):233–246); permission conveyed through Copyright Clearance Center, Inc. [23] …”

Section: Extended-release Oxycodone With Deterx Technology: a Microspmentioning

confidence: 99%

“…2Oxycodone DETERx plasma concentration over time: comparison of intact capsule administration with a sprinkled capsule contents, b chewed capsule contents, and c crushed capsule contents. b and c were adapted with permission from [23]. SD standard deviation …”

Section: Dosing Considerations and Optionsmentioning

confidence: 99%

“…Alternatively, patients may sprinkle the capsule contents into a cup, then pour the microspheres directly into the mouth and swallow [21, 23]. Patients should be instructed to rinse their mouths to ensure all microspheres have been swallowed.…”

Section: Dosing Considerations and Optionsmentioning

confidence: 99%

“…The safety of oxycodone DETERx was evaluated in multiple phase 1 single-dose studies [22, 23, 25–27] and one randomized, double-blind, phase 3 study [24]; the treatment-emergent adverse events (AEs) reported during the titration and maintenance portions of the phase 3 study are shown in Table 3. Treatment-related AEs were reported in 366 (50%) patients in the open-label titration phase.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…In accordance with the FDA guidance category 1 recommendations [16], in vitro physical and chemical manipulation studies were performed to evaluate the abilities of different methods commonly used by abusers to defeat the ER properties of oxycodone DETERx (Table 4) [23, 28]. When compared with immediate-release (IR) oxycodone tablets, oxycodone DETERx was less susceptible to the effects of grinding, crushing, and extraction using a variety of tools and solvents [23, 28].…”

Section: Abuse Deterrencementioning

confidence: 99%

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Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

Gudin

2016

Pain Ther

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BackgroundExtended-release (ER) opioid analgesics are commonly used to provide safe and effective pain relief to treat pain severe enough to require around-the-clock, long-term dosing. These ER opioid formulations usually contain more drug per dosage unit than immediate-release (IR) agents, and therefore bring with them challenges related to both opioid abuse and misuse, often through manipulation of the dosage form. Oxycodone DETERx® (Xtampza® ER, Collegium Pharmaceutical, Inc.) is a novel abuse-deterrent, ER formulation developed to deter common methods of manipulation. In addition to having abuse-deterrent properties, oxycodone DETERx was developed to provide alternative modes of administration for patients with chronic pain and difficulty swallowing.ScopeUsing published articles, abstracts, and prescribing information, data supporting the use of oxycodone DETERx are reviewed.FindingsOxycodone DETERx was effective at reducing chronic pain in patients enrolled in a pivotal clinical trial, and had a tolerability profile expected of opioids. In addition to administration of the intact capsule, oxycodone DETERx can also be administered by sprinkling directly into the mouth from a dosing cup, onto soft foods, or through nasogastric or gastrostomy tubes, thus providing flexible dosing options for patients who have difficulty swallowing. In vitro studies demonstrated the reduced ability of oxycodone DETERx to be manipulated by common techniques used by abusers to defeat the ER characteristics or prepare the formulation for injection. Pharmacokinetic studies demonstrated that the ER characteristics of oxycodone DETERx are maintained if chewed or crushed. As a result, oxycodone DETERx is currently the only ER-formulated opioid without a boxed warning against crushing or chewing. Human abuse-potential studies conducted in a population of recreational opioid users demonstrated lower drug-liking scores for oxycodone DETERx administered intranasally and orally when compared with IR oxycodone.FundingCollegium Pharmaceutical, Inc.

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Section: Extended-release Oxycodone With Deterx Technology: a Microspmentioning

confidence: 99%

Section: Dosing Considerations and Optionsmentioning

confidence: 99%

Section: Dosing Considerations and Optionsmentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

Section: Abuse Deterrencementioning

confidence: 99%

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Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

Gudin

2016

Pain Ther

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

Kopecky

Fleming

Levy‐Cooperman³

et al. 2016

The Journal of Clinical Pharma

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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.

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Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer

McDonald

Spencer

Willey

et al. 2020

Support Care Cancer

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Impact of physical manipulation on in vitro and in vivo release profiles of oxycodone DETERx®: An extended-release, abuse-deterrent formulation

Abstract: These mechanical manipulation and PK studies demonstrated that DETERx beads retained their ER properties after mechanical tampering and chewing by study subjects.

Cited by 27 publications

References 12 publications

Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

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

Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer

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Impact of physical manipulation on in vitro and in vivo release profiles of oxycodone DETERx®: An extended-release, abuse-deterrent formulation

Abstract: These mechanical manipulation and PK studies demonstrated that DETERx beads retained their ER properties after mechanical tampering and chewing by study subjects.

Cited by 27 publications

References 12 publications

Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain

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

Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer

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Product

Resources

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