NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study.
BACKGROUND
Tardive 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.


METHODS
Male 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.


RESULTS
Two 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.


CONCLUSIONS
NBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway.
Neurocrine Biosciences, San Diego, California, USA.
Christopher F
CF
O'Brien
Neurocrine Biosciences, San Diego, California, USA.
Roland
R
Jimenez
University of South Florida, Tampa, Florida, USA.
Robert A
RA
Hauser
Emory University, Atlanta, Georgia, USA.
Stewart A
SA
Factor
Neurocrine Biosciences, San Diego, California, USA.
Joshua
J
Burke
Biscayne Bay Institute, Miami, Florida, USA.
Daniel
D
Mandri
Research in Miami, Miami, Florida, USA.
Julio C
JC
Castro-Gayol
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D050492:Vesicular Biogenic Amine Transport Proteins / Q000037:antagonists & inhibitors*; D055815:Young Adult
D050492:Vesicular Biogenic Amine Transport Proteins; C000603978:valbenazine; D014633:Valine; D013747:Tetrabenazine
antipsychotic drugs; randomized controlled trial; tardive dyskinesia; vesicular monoamine transporter (VMAT2)