SAFETY AND TOLERABILITY OF THE FREE-RADICAL SCAVENGER OPC-14117 IN HUNTINGTONS-DISEASE

Oxidative damage due to free-radical generation in the setting of unde rlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors cond ucted a randomized, double-blind, placebo-controlled, multicenter tria l of the tolerability of OPC-14117, a lipophilic free-radical scavenge r that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed b y the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of bli nded withdrawal of the study drug. Tolerability was measured by the pr oportion of patients completing the initial 12-week course of treatmen t on their originally assigned regimen. Sixty-four patients were enrol led in the study, 56 of whom completed the 12 weeks of treatment. Trea tment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 m g/d) due to asymptomatic but persistent serum elevations of liver tran saminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of p ersistent vomiting. There were no significant differences between trea tment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, eleva tions of liver transaminase suggested that continued surveillance moni toring is warranted in conducting more long-term studies of this antio xidant therapy.