Efficacy and safety evaluation of an extended-release morphine sulfate formulation with sequestered naltrexone for the treatment of osteoarthritis

Illicit use of prescription opioids has caused need for products that discourage abuse.^1,2 ALO-01 capsules, an abuse-deterrent product under investigation for treatment of chronic moderate-to-severe pain, contain pellets of extended-release morphine sulfate surrounding a core of sequestered naltrexone intended to be released following tampering (crushing/chewing/dissolution). This multicenter, prospective, randomized, double-blind, crossover study compared pharmacokinetics, efficacy, and safety of ALO-01 with KADIAN^®, a marketed extended-release morphine sulfate product, in adults (N=113) with moderate-to-severe osteoarthritis pain. Outcome measures included pain-intensity ratings, Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; Patient Global Assessment of Medication (scale 1-5; poor-excellent); and morphine and naltrexone pharmacokinetics. After washout-period to induce pain-flare (intensity ≥5, 0-10 scale; 0=no pain, 10=worst pain), patients were dose-titrated with KADIAN^®, (20mg-160mg BID) until pain-intensity score ≤3 was reached, then randomized to 2 (crossover) 14-day treatments with KADIAN^® and ALO-01, each followed by 7-day open-label KADIAN^® treatment. Most patients were women (68.5%) and white (88.3%); median age was 57.0 years. Mean pain-intensity scores were similar during treatment (Day 14: KADIAN^®, 2.4; ALO-01, 2.3, p=0.31), as were Brief Pain Inventory scores, and WOMAC mean pain, physical function, and composite change from baseline scores. Most patients (KADIAN^®, 78.9%; ALO-01, 91.5%) rated medications as good-to-excellent. Morphine exposure at steady-state was similar (95% CI, 0.82-1.07 for KADIAN^®/ALO-01 AUC_0-12). Plasma naltrexone levels were below the limit of quantification for most patients (82.1%) treated with ALO-01; when detected, levels were just above the limit of quantification and had no impact on decrease in pain scores. Most common adverse events during the double-blind phase were constipation (KADIAN^®, 12.7%; ALO-01, 15.5%), nausea (KADIAN^®, 8.5%; ALO-01, 9.9%), and somnolence (KADIAN^®, 8.5%; ALO-01, 9.9%), and were of mild-to-moderate intensity. ALO-01 provided similar pain relief as KADIAN^®; both medications were rated good-to-excellent.

¹Wright;DrugAlcoholDepend;2006.

²Kuehn;JAMA;2007.

Supported by Alpharma Pharmaceuticals LLC