|
Abstract
|
OBJECTIVE. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets
Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (E max ) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to E max (TE max ) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking).
Results. Thirty-eight participants completed the study. Median Drug Liking VAS E max was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TE max was significantly shorter after treatment with manipulated morphine ER compared with intact ( P < 0.0001) or manipulated ( P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9).
Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking E max compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products.
Language: en |