Subjective effects and safety of whole and tampered morphine sulfate and naltrexone hydrochloride (ALO-01) extended-release capsules versus morphine solution and placebo in experienced non-dependent opioid users: A randomized, double-blind, placebo-controlled, crossover study

Joseph Stauffer, Beatrice Setnik, Marta Sokolowska, Myroslava Romach, Franklin Johnson, Edward Sellers

Research output: Contribution to journalArticle

Abstract

Background and Objective: Given the dual public health challenges of undertreated pain and opioid abuse, there is a need to reduce attractiveness of opioid analgesics to drug abusers. ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules, indicated for treatment of chronic, moderate to severe pain, contain polymer-coated pellets of morphine, each with a core of sequestered naltrexone intended for release only upon tampering (crushing). The purpose of this study was to assess the pharmacodynamic effects (including drug-liking and euphoria) of whole and crushed ALO-01 versus morphine sulfate solution (MSS) and placebo. Methods: This was a randomized, double-blind, placebo-controlled, tripledummy, four-way crossover study carried out at a clinical research centre. Participants were experienced non-dependent opioid users. Subjects were given either two ALO-01 60 mg capsules, crushed pellets from two ALO-01 60mg capsules, MSS 120 mg or placebo; there was a 14- to 21-day washout between treatments. The primary endpoints were drug-liking visual analogue scale score, scores on items from the Addiction Research Center Inventory (ARCI) and Cole/ARCI scales characterizing abuse potential and euphoria, and pupil diameter as measured by pupillometry. Results: Morphine plasma concentrations were similar after ALO-01 crushed and MSS, with a median time to reach maximum plasma concentration (tmax) of 1.1 and 1.2 hours, respectively; the plasma naltrexone median tmax was 1.1 hours after ALO-01 crushed. By comparison, the median tmax for morphine with ALO-01 whole was 8.1 hours. The maximum effect (Emax) of MSS was significantly greater than placebo on pupillometry and the subjective measures (all p < 0.001). ALO-01 whole and crushed produced lower Emax values and flatter effect-time profiles for subjective measures and caused less pupillary constriction than MSS. Conclusions: The results of this study demonstrated that ALO-01, whether taken orally whole as intended or tampered with by crushing and taken orally, had reduced desirability compared with MSS.

Original languageEnglish (US)
Pages (from-to)777-790
Number of pages14
JournalClinical Drug Investigation
Volume29
Issue number12
DOIs
StatePublished - Nov 17 2009

ASJC Scopus subject areas

  • Pharmacology (medical)

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