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.