(236) Relative bioavailability of plasma naltrexone from crushed ALO-01 (an investigational, abuse-deterrent, extended-release, morphine sulfate formulation with sequestered naltrexone) to a naltrexone oral solution

Nonprescription use of opioids has increased dramatically, resulting in a need for products with reduced abuse potential. ALO-01, an investigational, extended-release, abuse-deterrent opioid formulation intended for moderate-to-severe chronic pain, contains polymer-coated extended-release morphine sulfate pellets with a sequestered core of naltrexone, an opioid antagonist. The formulation is designed to release naltrexone upon tampering (crushing/chewing/dissolution) to reduce morphine-induced euphoria. This study compares the oral bioavailability of naltrexone released after crushing ALO-01 pellets with that of an equivalent amount of naltrexone solution. This single-dose, open-label, randomized, 3-period, 3-treatment crossover study included 24 subjects aged 18-55 years who took 1 of 3 oral treatments: crushed ALO-01 pellets (ALO-01C), whole intact ALO-01 (ALO-01W), or naltrexone solution (N) following a 10-hour overnight fast. Subjects received each of the 3 treatments, which were separated by a washout of 14 days. Blood for plasma naltrexone determinations was drawn at scheduled times from 0-168 hours postdose. Twenty-three subjects completed the study. Naltrexone absorption rate (median Tmax: 1.0 for both) and mean concentration-time curves from ALO-01C and N were similar. Maximal and systemic exposure of naltrexone released from ALO-01C or N were bioequivalent (90% confidence intervals for Cmax and AUC between 80%125%). Plasma naltrexone was below the limit of quantification following ALO-01W administration. Most adverse events were mild (87/89) or moderate (2/89), and were gastrointestinal-related. Crushing ALO-01 pellets successfully released the sequestered naltrexone to a level bioequivalent with that of naltrexone oral solution and rendered it available to reduce morphine-induced euphoria. Supported by a grant from Alpharma Pharmaceuticals LLC. (1. Katz, Clin J Pain, 2007;23(2):103118.)