Researchers have found that in patients with schizophrenia, 48 weeks of valbenazine resulted in sustained improvements in tardive dyskinesia. These results, combined with results from mood disorder subjects and the long-term safety profile, indicate that long-term valbenazine can be beneficial in managing tardive dyskinesia. These findings were presented at the American Psychiatric Association (APA) 2017 Annual Meeting.
John M. Kane, MD, professor and chairman of the Department of Psychiatry at the Hofstra Northwell School of Medicine, Hempstead, New York, and colleagues conducted the KINECT 3 trial, evaluating the effects of valbenazine on patients with schizophrenia or mood disorder who received up to 48 weeks of treatment.
The KINECT 3 trial included 3 segments: a 6-week, double-blind, placebo-controlled period (205 completers), a 42-week valbenazine extension period (124 completers), and a 4-week washout period (121 completers). Participants were allowed to continue stable antipsychotic medication regimens during the study.
Participants entering the first phase were randomly assigned 1:1:1 to 80 mg valbenazine once daily, 40 mg valbenazine once daily, or placebo. Participants entering the second phase were rerandomized (blinded) 1:1 from placebo to 80 or 40 mg valbenazine or continued treatment with valbenazine at the same dose.
Measures to assess efficacy included average change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7), average Clinical Global Impression of Change-tardive dyskinesia score, AIMS responders (participants with 50% or higher score reduction from baseline), and Clinical Global Impression of Change-tardive dyskinesia responders (participants with a score of 2 or less [“much improved” or “very much improved”]).
At the end of the first phase (6 weeks), AIMS mean score improvements were greater in the groups receiving valbenazine compared with the placebo group (80 mg group: −2.9, d=0.88; 40 mg group: −1.6, d=0.52; placebo group: +0.3). AIMS score changes at the end of phase 2 (week 48) showed continued improvements in tardive dyskinesia (80 mg group: −4.2; 40 mg group: −2.5). At the end of the washout period, scores were returning to normal, indicating that tardive dyskinesia was returning.
AIMS responder rates (50% or higher score reduction) were also greater in the valbenazine groups compared with the placebo at week 6 (80 mg group: 40.9%, number needed to treat [NNT]=4; 40 mg group: 26.2%, NNT=6; placebo group: 9.3%). AIMS responder rates were also increased at week 48 (80 mg group: 50.0%; 40 mg group: 26.2%) and were decreased after the washout period (80 mg group, 21.6%; 40 mg group, 9.5%). CGI-tardive dyskinesia responder rates followed similar patterns at week 6 (80 mg group: 29.5%, NNT=17; 40 mg group: 33.3%, NNT=10; PBO, 23.3%), week 48 (80 mg group: 73.7%; 40 mg group: 58.1%), and week 52 (80 mg group, 29.7%; 40 mg group: 33.3%).
“Sustained [tardive dyskinesia] improvements were found in subjects with [schizophrenia] who received up to 48 weeks of [valbenazine], with [tardive dyskinesia] reverting toward baseline when assessed four weeks after treatment withdrawal,” the researchers concluded.
Kane JM, Correll CU, Liang GS, Burke J, O’Brien CF. Efficacy of valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and schizophrenia or schizoaffective disorder. Presented at: American Psychiatric Association (APA) 2017 Annual Meeting; May 20-24, 2017; San Diego, CA.