ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules in the treatment of chronic pain of osteoarthritis of the hip or knee: pharmacokinetics, efficacy, and safety.

Abstract

UNLABELLED:

ALO-01 (EMBEDA [morphine sulfate and naltrexone hydrochloride] extended-release capsules [King Pharmaceuticals, Inc, Bridgewater, NJ]), indicated for chronic moderate-to-severe pain, is designed to release naltrexone upon tampering (eg, by crushing), reducing morphine-induced subjective effects. This multicenter, randomized, double-blind, crossover study assessed pharmacokinetics, efficacy, and safety of ALO-01 and compared them with extended-release morphine sulfate (ERMS, KADIAN [morphine sulfate extended-release] capsules [Actavis US, Morristown, NJ]) in adults (N = 113) with osteoarthritis pain. Study periods included washout until pain flare (intensity > or =5, 0 to 10; 0 = no pain, 10 = worst pain); dose titration with ERMS (20 to 160mg BID); and randomization to 2 (crossover) 14-day treatment periods with ERMS or ALO-01, separated by 7 days of open-label ERMS. Assessments included pharmacokinetics (morphine, naltrexone), pain scores (0 to 10), Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; Patient Global Assessment of Medication (1 to 5; poor to excellent). Mean score at pain flare was 7.1. Morphine exposure from both formulations at steady state was similar. Plasma naltrexone concentrations were below limit-of-quantification for most patients and, when present, did not impact pain scores. During treatment, mean pain intensity (day 14: ERMS, 2.4; ALO-01, 2.3, P = .31), WOMAC change-from-baseline (mean pain, physical function, composite scores), and adverse event frequency were similar. ALO-01 and ERMS provided similar relief of osteoarthritis pain.

PERSPECTIVE:

We present data demonstrating that ALO-01 has steady-state morphine exposure, efficacy, and safety similar to marketed ERMS capsules. Results highlight the potential for morphine in ALO-01 to manage moderate-to-severe osteoarthritis pain, while the sequestered naltrexone does not interfere with efficacy.

• Authors: Nathaniel Katz, Stephen Sun, Franklin Johnson, Joseph Stauffer
• Journal: The journal of pain (J Pain) Vol. 11 Issue 4 Pg. 303-11 (Apr 2010) ISSN: 1528-8447 [Electronic] United States
• PMID: 19944650 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Analgesics, Opioid
• Drug Combinations
• Illicit Drugs
• Narcotic Antagonists
• morphine, naltrexone combination
• Naltrexone
• Morphine

Topics

• Adult
• Aged
• Aged, 80 and over
• Analgesics, Opioid (administration & dosage, adverse effects, pharmacokinetics)
• Chronic Disease (drug therapy)
• Cross-Over Studies
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Illicit Drugs (pharmacokinetics)
• Male
• Middle Aged
• Morphine (administration & dosage, adverse effects, pharmacokinetics)
• Morphine Dependence (drug therapy, prevention & control)
• Naltrexone (administration & dosage, adverse effects, pharmacokinetics)
• Narcotic Antagonists (administration & dosage, adverse effects, pharmacokinetics)
• Osteoarthritis, Hip (drug therapy, physiopathology)
• Osteoarthritis, Knee (drug therapy, physiopathology)
• Pain Measurement (drug effects)
• Treatment Outcome