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.
Author(s): Katz N, Sun S, Johnson F, Stauffer J.
Affiliation(s): Tufts University School of Medicine, Boston, Massachusetts; Analgesic Research,
Needham, MA 02494, USA. nkatz@analgesicresearch.com
Publication date & source: 2010, J Pain. , 11(4):303-11
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.
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