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

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.

Isolation of enterocin SE-K4-encoding plasmid and a high enterocin SE-K4 producing strain of Enterococcus faecalis K-4.

Enterococcus faecalis K-4, which produces a class IIa bacteriocin, enterocin SE-K4, carries two plasmids, pEK4S (approximately 60 kb) and pEK4L (approximately 75 kb). Plasmid-curing experiments showed that pEK4S was involved in the production of and immunity to enterocin SE-K4 in strain K-4. A derivative strain, M6, with pEK4S produced a higher amount of enterocin SE-K4 than the parental strain K-4, although its growth rate was lower than that of parental strain K-4. Phenotypic changes in strain M6 are attributed to an increase in plasmid copy number.