title: Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: PRA Health Sciences, Salt Lake City, Utah, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: PRA Health Sciences, Salt Lake City, Utah, USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.affiliation: Egalet Corporation, Wayne, Pennsylvania, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lawler
authors.affiliation: Egalet Corporation, Wayne, Pennsylvania, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Lindhardt
authors.affiliation: Egalet Corporation, Wayne, Pennsylvania, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Dayno
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D013287:Illicit Drugs; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009293:Opioid-Related Disorders / Q000453:epidemiology*; D010098:Oxycodone / Q000008:administration & dosage*; D010414:Pennsylvania / Q000453:epidemiology; D015990:Placebo Effect; D015995:Prevalence; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013287:Illicit Drugs; D009020:Morphine; D010098:Oxycodone
keywords: Abuse Deterrent; Drug Liking; Extended Release; Human Abuse Potential; Morphine