Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group.
Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger 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 by 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 blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. 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 persistent vomiting. There were no significant differences between treatment 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, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy.
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid; D005609:Free Radicals; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D017665:Hydroxyl Radical; D007189:Indans / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010879:Piperazines / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid
D016166:Free Radical Scavengers; D005609:Free Radicals; D007189:Indans; D009419:Nerve Tissue Proteins; D010879:Piperazines; D017665:Hydroxyl Radical; C074852:OPC 14117