Efficacy & Safety Study of Nonracemic Methadone for the Relief of Chronic Peripheral Neuropathic Pain

Objectives: * To evaluate effect of the three doses of the non-racemic methadone HCl on the metrics of pain intensity in comparison to placebo. * To determine minimally effective and maximally tolerated doses of non-racemic methadone HCl for the treatment of diabetic peripheral neuropathic pain. * To evaluate safety and tolerability of non-racemic methadone HCl therapy. Study Design: This is a pilot efficacy and safety study comprised of two parts. Part I is a double-blind, placebo-controlled, crossover study of three daily doses (15 mg, 30 mg and 40 mg) of non-racemic methadone compared with placebo. Two lower doses (15 mg and 30 mg) will be administered for 1 week. The final dose (40 mg) will be administered for 2 weeks. After receiving three consecutive doses of the assigned drug the subjects will be switched to another regimen. Two 28-day treatment periods will be separated by a 14-day washout (drug-free) interval. Subjects will be randomly assigned to one of the two treatment sequences: Sequence 1: non-racemic methadone HCl (Period 1) followed by Placebo (Period 2); Sequence 2: Placebo (Period 1) followed by non-racemic methadone HCl (Period 2). Subjects completing Part I will be enrolled into the open-label, single-arm extension. Subjects discontinuing the study while on placebo may also be eligible for the enrollment. During the 6-week extension phase (Part II of the study) subjects will be treated with non-racemic methadone HCl with continuous dose titration driven by the clinical response (degree of pain relief) and reported adverse events. The Parts I and II will be separated by a 14-day washout (study drug-free) interval. Number of Patients: Up to fifty (50) subjects diagnosed with neuropathic pain associated with diabetic peripheral neuropathy will be enrolled in the study; approximately 30 subjects are expected to complete Study Part I. Enrollment will be terminated when this completion target is achieved. Study Duration: The duration of Study Part I is approximately 12 weeks, the duration of Study Part II is approximately 6 weeks. A total study duration (including screening and final evaluations) is expected to be approximately 20 weeks.