Tufts University School of Medicine, Boston, Massachusetts; Analgesic Research, Needham, MA 02494, USA.
J Pain. 2010 Apr;11(4):303-11. doi: 10.1016/j.jpain.2009.07.017. Epub 2009 Nov 27.
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.
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.
评估 ALO-01（King 制药公司，Bridgewater，NJ 的硫酸吗啡和盐酸纳曲酮控释胶囊[EMBEDA]）治疗慢性中重度疼痛的药代动力学、疗效和安全性，并与市售硫酸吗啡控释胶囊（Actavis US，Morristown，NJ 的 KADIAN[硫酸吗啡控释胶囊]）进行比较。
这是一项多中心、随机、双盲、交叉研究，纳入 113 例骨关节炎疼痛成人患者。研究期间包括洗脱直至疼痛发作（强度≥5，0 到 10；0 表示无痛，10 表示最痛）；用 ERMS 滴定剂量（20 到 160mg，bid）；随机分为 2 个（交叉）14 天的 ERMS 或 ALO-01 治疗期，间隔 7 天开放标签 ERMS。评估包括药代动力学（吗啡、纳曲酮）、疼痛评分（0 到 10）、西部安大略省和麦克马斯特大学骨关节炎指数；患者对药物的整体评估（1 到 5；差到优）。疼痛发作时的平均评分是 7.1。两种制剂在稳态时的吗啡暴露量相似。大多数患者的血浆纳曲酮浓度低于定量下限，当存在时，对疼痛评分没有影响。在治疗期间，平均疼痛强度（第 14 天：ERMS，2.4；ALO-01，2.3，P=.31）、WOMAC 基线变化（平均疼痛、躯体功能、综合评分）和不良事件频率相似。ALO-01 和 ERMS 提供了相似的骨关节炎疼痛缓解。
我们提供的数据表明，ALO-01 具有与市售 ERMS 胶囊相似的稳态吗啡暴露量、疗效和安全性。结果突出了 ALO-01 中吗啡管理中重度骨关节炎疼痛的潜力，而被隔离的纳曲酮不干扰疗效。
