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.

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, triple-dummy, 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 60 mg 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 (t(max)) of 1.1 and 1.2 hours, respectively; the plasma naltrexone median t(max) was 1.1 hours after ALO-01 crushed. By comparison, the median t(max) for morphine with ALO-01 whole was 8.1 hours. The maximum effect (E(max)) of MSS was significantly greater than placebo on pupillometry and the subjective measures (all p < 0.001). ALO-01 whole and crushed produced lower E(max) values and flatter effect-time profiles for subjective measures and caused less pupillary constriction than MSS.

CONCLUSION:

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.

• Authors: Joseph Stauffer, Beatrice Setnik, Marta Sokolowska, Myroslava Romach, Franklin Johnson, Edward Sellers
• Journal: Clinical drug investigation (Clin Drug Investig) Vol. 29 Issue 12 Pg. 777-90 ( 2009) ISSN: 1173-2563 [Print] New Zealand
• PMID: 19888784 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Capsules
• Delayed-Action Preparations
• Drug Combinations
• Narcotic Antagonists
• Pharmaceutical Solutions
• Naltrexone
• Morphine

Topics

• Adult
• Analgesics, Opioid (administration & dosage, adverse effects, pharmacology)
• Capsules
• Cross-Over Studies
• Delayed-Action Preparations
• Double-Blind Method
• Drug Combinations
• Euphoria (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Morphine (administration & dosage, adverse effects, pharmacology)
• Naltrexone (administration & dosage, adverse effects, pharmacology)
• Narcotic Antagonists (administration & dosage, adverse effects, pharmacology)
• Pharmaceutical Solutions
• Pupil (drug effects)
• Time Factors
• Young Adult