A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER

• Published in: Pain medicine (Malden, Mass.) Vol. 18; no. 7; pp. 1303 - 1313
• Main Authors: Webster, Lynn R., Pantaleon, Carmela, Shah, Manish S., DiFalco, Ray, Iverson, Matthew, Smith, Michael D., Kinzler, Eric R., Aigner, Stefan
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.2017
• Subjects: Abuse-Deterrent Formulations - methods; Administration, Intranasal; Adult; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - chemistry; Cross-Over Studies; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Double-Blind Method; Double-blind studies; Drug abuse; Drug Compounding; Female; Follow-Up Studies; Humans; Intranasal administration; Male; Morphine; Morphine - administration & dosage; Morphine - chemistry; Narcotics; Opioid-Related Disorders - drug therapy; Opioid-Related Disorders - psychology; Opioids; Sulfates; Young Adult; Snorting; Pain; Opioid Abuse; Abuse Deterrent
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1093/pm/pnw213

Abstract Objective. Misuse and abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-deterrent formulations of prescription opioids are designed to reduce intentional misuse, abuse, and prescription opioid–related death. A novel extended-release (ER) formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine (P < .0001). There was no significant difference when comparing the Emax for crushed intranasal vs intact Morphine ARER. When comparing crushed intranasal Morphine ARER with ER morphine, subjects reported lower mean scores for good effects of the drug, drug high, and overall drug liking, as well as a lower desire to use Morphine ARER again. Other than adverse events associated with intranasal administration of a drug, all adverse events were typical of those reported for opioid-containing drugs. Conclusions. Overall, these data suggest that Morphine ARER has a lower abuse potential via the intranasal route of administration when compared with ER morphine.