title: Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.
abstract: OBJECTIVE
  To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets.
  
  
  METHODS
  A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking.
  
  
  RESULTS
  Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2).
  
  
  CONCLUSIONS
  All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine.
authors.affiliation: PRA Health Sciences, Salt Lake City, Utah.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.affiliation: PRA Health Sciences, Salt Lake City, Utah.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
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: D000075162:Abuse-Deterrent Formulations / Q000379:methods*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D013607:Tablets
chemical_list: D000075162:Abuse-Deterrent Formulations; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013607:Tablets; D009020:Morphine
keywords: Abuse Potential; Abuse-Deterrent; Extended-Release; Human Abuse Potential; Intranasal; Morphine