• Christopher F O'Brien, Roland Jimenez, Robert A Hauser, Stewart A Factor, Joshua Burke, Daniel Mandri, and Julio C Castro-Gayol.
• Neurocrine Biosciences, San Diego, California, USA.
• Mov. Disord. 2015 Oct 1; 30 (12): 1681-7.

BackgroundTardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia.MethodsMale and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change-Tardive Dyskinesia score assessed by the blinded investigator.ResultsTwo hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change-Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted.ConclusionNBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway.© 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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