Novel Oxycodone Abuse-Deterrant Formulation Shows Comparable Efficacy With IR Oxycodone
Only 1 immediate-release formulation (RoxyBondTM) with abuse-deterrent formulation labeling has been approved by the US Food and Drug Administration.
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LAS VEGAS — Oxycodone ARIR (RoxyBond™), a novel abuse-deterrent formulation (ADF) of immediate-release (IR) oxycodone, may have comparable safety and efficacy to IR oxycodone, according to a study presented during the 2018 PAINWeek conference, held September 4-8.
Only 1 IR formulation (RoxyBond) with ADF labeling (vs 7 extended-release ADF formulations) has been approved by the US Food and Drug Administration. RoxyBond was designed to prevent intravenous and intranasal abuse. Investigators sought to compare the bioavailability profiles of IR oxycodone and oxycodone ARIR.
A total of 75 healthy participants were enrolled in a single-dose, open-label, randomized, 3-treatment, 3-period, 6-sequence crossover study comparing RoxyBond and IR oxycodone. After fasting for ≥10 hours, individuals were administered IR oxycodone or oxycodone ARIR 30 mg—along with preadministration and postadministration naltrexone 50 mg to attenuate drug-related side effects—followed by a 4-day washout period before administration of the following dose. Oxycodone plasma concentrations were measured before and after (up to 24 hours) administration.
Among the pharmacokinetic parameters examined were the area under the plasma concentration-time curve (AUC0-t and AUC0-∞), the maximum plasma concentration (Cmax) and the Cmax-associated time (Tmax). Researchers calculated 90% CIs and geometric mean ratios for both formulations' Cmax and AUC measurements, with the therapies considered equivalent if the 90% CIs fell within the 80% to 125% regulatory bioequivalence range. Adverse events (AEs) and laboratory, clinical, or electrocardiographic abnormalities were also reported.
Of 75 initial study participants, 58 completed all study treatments and were considered for further analysis. The RoxyBond mean Cmax was 14% lower compared with the Cmax for IR oxycodone (57.8 ng/mL vs 67.7 ng/mL, respectively, and both AUC measures were 4% lower for oxycodone ARIR vs IR oxycodone. In terms of total exposure, both formulations fell within the regulatory range, with an AUC0-t at 92.5% to 98.7% and an AUC0-∞ at 92.8% to 98.9%. The Cmax 90% CI at 78.8% to 94.3% was outside of the bioequivalence range, and the oxycodone ARIR median Tmax was 29 minutes more than the Tmax for IR oxycodone.
RoxyBond was associated with more AEs than IR oxycodone (20% vs 11%, respectively), with gastrointestinal and central nervous system complaints most common. All AEs were considered typical of those seen in patients taking opioids, and all were rated as mild to moderate in severity.
Lynn Webster, MD, vice president of scientific affairs at PRA Health Sciences in Salt Lake City and lead author of the study, noted, "Although the Cmax of RoxyBond was slightly lower than the Cmax for IR oxycodone, it is expected to have the same efficacy. "Post-approval studies assessing the impact of the abuse deterrent properties on abuse of the product" are mandated, she added.
Webster L, Kinzler ER, Pantaleon C, Iverson M, Aigner S. The relative bioavailability of oxycodone ARIR (RoxyBondTM), a novel abuse-deterrent formulation of immediate-release oxycodone, compared with immediate-release oxycodone. Presented at: PAINWeek 2018; September 4-8, 2018; Las Vegas, NV. Poster 76.
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