VANCOUVER, BC—Once-daily valbenazine 25mg–75mg for 6 weeks significantly reduced severity of tardive dyskinesia in patients with schizophrenia, schizoaffective disorder, depression, and bipolar disorder, a randomized Phase 2 trial reported at the 68th AAN Annual Meeting.
The study also showed use of blinded, central raters of the Abnormal Involuntary Movement Scale (AIMS) to be “highly sensitive in detecting change, capable of reducing variability and therefore should be considered in the design” of future trials of tardive dyskinesia, noted Stewart Factor, DO, Vance Lanier Chair of Neurology at Emory University School of Medicine and Director of the Emory Comprehensive Parkinson’s Disease Center and the Movement Disorders Program, Atlanta, GA.
The KINECT 2 study assessed the efficacy and safety of valbenazine (NBI-98854), a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor, in patients with schizophrenia, schizoaffective disorder, and mood disorder with tardive dyskinesia.
In the multicenter trial, patients were randomly assigned to valbenazine or placebo at a 1:1 ratio for 6 weeks. Based on clinical response, the once-daily dose of valbenazine was titrated from 25mg–50mg at Week 2 and from 50mg–75mg at Week 4.
The primary endpoint was change in AIMS score from baseline to Week 6.
“AIMS videos were scored by central raters blinded to treatment arm and study visit sequence,” Dr. Factor reported. Key secondary endpoints included Clinical Global Impression of Change-TD (CGI-TD) and safety.
All patients with at least one post-randomization AIMS assessment were included in the pre-specified efficacy analysis. Among these 89 patients, the primary endpoint showed significant reduction in AIMS favoring valbenazine over placebo (-2.6 vs. -0.2 LS mean change; P=0.0005).
Responder rate, defined as an AIMS reduction of ≥50% from baseline, was 49% for patients treated with valbenazine vs. 18% in the placebo arm (P=0.002).
CGI-TD, as assessed by site investigator, showed significant improvement—“much improved” or “very much improved”—with valbenazine, 67%, compared with 16% for placebo (P<0.0001).
No treatment-related serious adverse events were observed, and adverse events were infrequent and included fatigue (5 in the valbenazine arm and 2 in the placebo arm) and headache (5 vs. 2, respectively). A total of 5 patients in each arm discontinued treatment early.