Long-Term Safety and Efficacy of Tetrabenazine in the Treatment of Chorea Associated with Huntington's Disease (P06.034)

Abstract

Objective: To assess long-term safety and efficacy of tetrabenazine for chorea associated with Huntington9s disease (HD). Background At study initiation (1979), tetrabenazine had not yet been approved in the US (2008). Design/Methods: In an open-label, Phase IIIb study conducted through an IND by the investigator (JJ), patients with hyperkinetic movement disorders were evaluated at Baylor College of Medicine. Tetrabenazine was used “last resort,” when other medications failed to provide satisfactory control. For HD-chorea patients, all previous chorea treatments were discontinued before tetrabenazine initiation. Patients were initially hospitalized, and tetrabenazine was started at 12.5 mg/day (≤300 mg/day maximum). Dosage was increased every 3 days, until a dosage-limiting AE occurred, and then down-titrated to greatest tolerated dosage. Visits were 6 weeks after hospitalization, and every 3 months thereafter. Responses were rated on a scale of 1–5, with 1 = marked chorea reduction, excellent improvement in function; 2 = moderate chorea reduction, very good improvement in function; 3 = fair chorea improvement, only mild improvement in function; 4 = poor or no response for chorea and function; and 5 = worsening chorea and some functional deterioration. 1 Dosage, efficacy, and AEs were collected at each visit. Results: Results for 217 patients with movement disorders who were treated with tetrabenazine have been reported. 1 By 2004, 98 HD-chorea patients were treated with tetrabenazine for a mean 3.1±2.5 years (range: 2 years. The 5 most common AEs possibly/probably related to tetrabenazine were somnolence (31%), insomnia (14%), depression (13%), akathisia (11%), and nervousness (10%). Of those with valid ratings, 75% had either marked or very good responses at their optimal dosages. Conclusions: Tetrabenazine provided sustained improvement in chorea and function, with AE rates comparable to what has been previously reported. 1 Jankovic J, et al. Neurology . 1988;38:391–4. Supported by: Lundbeck Inc. Disclosure: Dr. Shen has received personal compensation for activities with Lundbeck Inc as an employee. Dr. Clarence-Smith has received personal compensation for activities with Lundbeck Research USA, Inc. Dr. Hunter has received personal compensation for activities with Lundbeck Research USA, Inc. as a consultant. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington9s Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc.