Evaluation of the abuse potential of an extended release hydrocodone bitartrate tablet formulated with OraGuard™ technology in non-dependent, recreational opioid users

This study examined the relative abuse potential of crushed and intact extended-release (ER) hydrocodone bitartrate tablets formulated with OraGuard™ technology as compared to immediate-release (IR) hydrocodone. Healthy adult subjects with a history of recreational opioid use who were not dependent on opioids were enrolled. After confirming that eligible subjects were able to tolerate a 45 mg dose of IR hydrocodone and differentiate the effects of hydrocodone from placebo, subjects were randomized to the double-blind crossover portion of the study in which abuse potential was assessed. Subjects received each of the following (one in each period with a 14-day washout between doses): intact 45 mg ER hydrocodone tablet, crushed 45 mg ER hydrocodone tablet, 45 mg IR hydrocodone powder in a noncarbonated beverage, and placebo. Relative abuse potential was assessed by a series of tests. The primary endpoint was maximum effect (E_max) of drug liking based on question 1 of the Drug Liking and Effects Questionnaire (DLEQ). Overall Drug Liking Visual Analog Scale (VAS) was a secondary endpoint. Safety and tolerability was assessed throughout the study. Forty-two subjects were enrolled into the relative abuse potential assessment. Intact ER hydrocodone demonstrated significantly lower drug liking compared with IR hydrocodone based on DLEQ E_max (53.9 vs. 85.2; p<0.001) and Overall Drug Liking VAS (49.2 vs. 75.0; p<0.001). Crushed ER hydrocodone also demonstrated significantly lower drug liking compared with IR hydrocodone when assessed by both measures (DLEQ E_max 66.9 vs. 85.2, p<0.001, and Overall Drug Liking VAS 59.0 vs. 75.0, p<0.001). Outcomes for other secondary measures were consistent with these results, suggesting that ER hydrocodone, either intact or crushed, may have a lower abuse potential compared to IR hydrocodone. No new safety signals were observed with ER hydrocodone and there were no serious adverse events during the study.