TY - JOUR
T1 - ALO-01 (Morphine Sulfate and Naltrexone Hydrochloride) Extended-Release Capsules in the Treatment of Chronic Pain of Osteoarthritis of the Hip or Knee
T2 - Pharmacokinetics, Efficacy, and Safety
AU - Katz, Nathaniel
AU - Sun, Stephen
AU - Johnson, Franklin
AU - Stauffer, Joseph
N1 - Funding Information:
Supported by King Pharmaceuticals, Inc , Bridgewater, New Jersey.
Funding Information:
Writing and editorial support was provided by Innovex Medical Communications , Parsippany, NJ. Funding for writing and editorial support was provided by King Pharmaceuticals, Inc . The authors gratefully acknowledge the scientific contributions of Linda G. Daly and George Wagner.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/4
Y1 - 2010/4
N2 - 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 ≥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.
AB - 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 ≥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.
KW - ALO-01
KW - chronic pain
KW - morphine
KW - naltrexone
KW - osteoarthritis
KW - tampering
UR - http://www.scopus.com/inward/record.url?scp=77949917186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949917186&partnerID=8YFLogxK
U2 - 10.1016/j.jpain.2009.07.017
DO - 10.1016/j.jpain.2009.07.017
M3 - Article
C2 - 19944650
AN - SCOPUS:77949917186
VL - 11
SP - 303
EP - 311
JO - Journal of Pain
JF - Journal of Pain
SN - 1526-5900
IS - 4
ER -