Presented at the 2013 AAPM Annual Meeting « Back

Assessing the Pharmacodynamic Effects of Oral and Intranasal Administration of Crushed Extended-Release Morphine/Naltrexone Capsules Versus Crushed Controlled-Release Morphine Tablets and Placebo in Nondependent Recreational Opioid Users

Beatrice Setnik, PhD, beatrice.setnik@pfizer.com¹, Kenneth W. Sommerville, MD¹, Veeraindar Goli, MD MBA FAAM¹, Glenn C. Pixton, MS¹, Naama Levy-Cooperman, PhD², Catherine A. Mills, MSc², Megan J. Shram, PhD², Ira Smith, MD CCFP², Ling Han, MS³, Lynn R. Webster, MD⁴, (1) Pfizer Inc., Cary, North Carolina, (2) INC Research, Toronto, Ontario, Canada, (3) Synteract, Inc., Calsbad, California, (4) CRILifetree, Salt Lake City, Utah

Introduction: Two abuse-potential studies compared the pharmacodynamic effects, including drug-liking and high, of crushed morphine sulfate/naltrexone extended-release (MSN, EMBEDA®) capsules (crushing releases the sequestered naltrexone) with crushed controlled-release morphine (MS) and placebo when administered orally or intranasally. Materials and Methods: Both IRB-approved studies (oral and intranasal) were randomized, double-blind, active- and placebo-controlled, single-dose (30mg intranasal, 120mg oral), 3-way crossover designs in healthy, nondependent, recreational opioid users. Outcome measures included subjective ratings (visual analog scales) of drug effects (primary endpoints were drug-liking and high), pupillometry, pharmacokinetics, and safety assessments. Results: Irrespective of administration route, crushed MSN was associated with significantly lower mean peak effect (Emax) scores and effect over 2 h (AUE0-2) on subjective ratings of drug-liking and high compared with crushed MS (P<0.001), but ratings of drug-liking and high for crushed MSN and crushed MS were significantly greater relative to placebo (P<0.05). A similar pattern of differences amongst treatments was found with the secondary subjective measures, take drug again and overall drug-liking. Peak pupil diameter was significantly larger for MSN versus MS (P<0.005). Peak morphine plasma concentrations (Cmax) were significantly lower and time to Cmax significantly longer for crushed MSN versus crushed MS when administered orally, but were similar following intranasal administration. Conclusions: When crushed and administered intranasally or orally to nondependent, recreational opioid users, MSN was associated with significantly lower ratings on subjective measures, including drug-liking and high, and significantly less pupil constriction compared with crushed MS. MSN also showed higher ratings versus placebo.

Funding: This study was sponsored by King Pharmaceuticals, Inc., which was acquired by Pfizer Inc. in March 2011. Medical writing support for the development of the abstract was provided by Vardit Dror, PhD, and Diane Hoffman, PhD, of UBC Scientific Solutions and was funded by Pfizer Inc.