Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group

Neurology. 1998 May;50(5):1366-73. doi: 10.1212/wnl.50.5.1366.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Free Radical Scavengers / adverse effects*
  • Free Radical Scavengers / blood
  • Free Radical Scavengers / cerebrospinal fluid
  • Free Radicals
  • Humans
  • Huntington Disease / blood
  • Huntington Disease / cerebrospinal fluid
  • Huntington Disease / drug therapy*
  • Hydroxyl Radical
  • Indans / adverse effects*
  • Indans / blood
  • Indans / cerebrospinal fluid
  • Lipid Peroxidation / drug effects*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Oxidation-Reduction
  • Piperazines / adverse effects*
  • Piperazines / blood
  • Piperazines / cerebrospinal fluid


  • Free Radical Scavengers
  • Free Radicals
  • Indans
  • Nerve Tissue Proteins
  • Piperazines
  • Hydroxyl Radical
  • OPC 14117