Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT)

Abstract

Aim: Valbenazine is approved in the US for treatment of tardive dyskinesia (TD); however, efficacy/safety data in Asian populations are lacking. We assessed the efficacy/safety of valbenazine in Japanese patients.

Methods: This phase II/III, multicenter, randomized, double-blind, placebo-controlled study (NCT03176771) included adult psychiatric patients with TD, who were randomly allocated to receive placebo or valbenazine (once-daily 40- or 80-mg) for a 6-week, double-blind period, after which the placebo group was switched to valbenazine for a 42-week extension. The primary endpoint was change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score at Week 6; clinical global impression of improvement of TD (CGI-TD) was also assessed.

Results: Of 256 patients, 86, 85, and 85 were allocated to the 40-mg valbenazine, 80-mg valbenazine, and placebo groups, respectively. Least-squares mean (95% confidence interval) change from baseline in AIMS score at Week 6 was -2.3 (-3.0 to -1.7) in the valbenazine 40-mg group, -3.7 (-4.4 to -3.0) in the 80-mg group, and -0.1 (-0.8 to 0.5) in the placebo group; both treatment groups showed statistically significant improvements vs. placebo. Patients switched to valbenazine at Week 6 showed similar improvements in AIMS scores, which were maintained to Week 48. Improvements in CGI-TD scores were observed for both treatment groups vs. placebo. Incidence of adverse events was highest in the 80-mg group; common events included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia, and tremor.

Conclusion: The efficacy/safety profile of valbenazine was similar to that of previous clinical trials, supporting its use for TD treatment in Japanese patients.

Keywords: abnormal involuntary movement scale; randomized controlled trial; tardive dyskinesia; valbenazine; vesicular monoamine transporter 2.

© 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Figures

Fig. 1

Study design. aPatients allocated to the 80‐mg dose initiated valbenazine at a daily dose of 40 mg for 7 days before uptitrating to 80 mg. bFor the extension period, patients who received 40‐ or 80‐mg valbenazine during the placebo‐controlled period continued at the same dose. Patients who received placebo during the placebo‐controlled period were randomly reallocated to either 40‐ or 80‐mg valbenazine for the extension period. PC, placebo‐controlled; VE, valbenazine extension.

Fig. 2

Patient disposition. TEAE, treatment‐emergent adverse event; ITT, intention‐to‐treat; PC, placebo‐controlled; VE, valbenazine extension.

Fig. 3

Change from baseline in AIMS total score by central assessment (A)a and percentage of patients with AIMS response (B) (intention‐to‐treat analysis set). aData are means ± standard errors. AIMS, Abnormal Involuntary Movement Scale; PC, placebo‐controlled; VE, valbenazine extension.

Fig. 4

Change in CGI‐TD score throughout the study (A)a and breakdown of patients by CGI‐TD categories (B)b (intention‐to‐treat analysis set). aData are means ± standard deviations. bNo patients were assessed as “very much worse” (category 7). CGI‐TD, clinical global impression of improvement of tardive dyskinesia; PC, placebo‐controlled; VE, valbenazine extension.