Objective: To assess the emergence of extrapyramidal symptoms (EPS) such as akathisia and parkinsonism in adults with a diagnosis of schizophrenia/schizoaffective disorder or mood disorder who received up to 48 weeks of valbenazine for treatment of tardive dyskinesia (TD).

Background: Valbenazine is a novel and selective vesicular monoamine transporter 2 (VMAT2) inhibitor that has been evaluated in several double-blind, placebo-controlled (DBPC) and long-term safety studies in subjects with TD.

Methods: The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 2 DBPC studies with an extension phase and 1 long-term safety study: KINECT (NCT01688037: 50 mg/day; 6‑week DBPC, 6-week open-label), KINECT 3 (NCT02274558: 80 or 40 mg/day; 6-week DBPC, 42-week extension), and KINECT 4 (NCT02405091: 80 or 40 mg/day; 48-week open-label). For LTE safety analysis, subjects from these studies were pooled into 2 dose groups (40 mg [included KINECT 50 mg group] and 80 mg). Concomitant treatment with a stable antipsychotic regimen was allowed in all the studies. Emergent EPS was monitored using reporting of treatment-emergent adverse events (TEAEs), the Barnes Akathisia Rating Scale (BARS), and the Simpson-Angus Scale (SAS) to assess drug-induced parkinsonism.

Results: The LTE population included 430 subjects (40 mg, n=200; 80 mg, n=230). Incidences of potential EPS-related TEAEs were as follows (total, 40 mg, 80 mg): akathisia (2.3%, 4.0%, 0.9%), tremor (2.3%, 2.0%, 2.6%), parkinsonism (0.5%, 0.5%, 0.4%), cogwheel rigidity (0.2%, 0%, 0.4%), muscle rigidity (0.2%, 0%, 0.4%). In subjects who reached the Week 48 visit, mean changes in BARS total score (40 mg, -0.6; 80 mg, -0.8) and global score (40 mg, -0.2; 80 mg, -0.4) were minimal and indicated no evidence of drug-induced akathisia. Mean changes in SAS global score (40 mg, -0.10; 80 mg, -0.11) were also minimal and indicated no evidence of drug-induced parkinsonism.

Conclusions: Although most subjects in these studies were taking an antipsychotic medication concomitantly with valbenazine (for up to 48 weeks), incidences of potential EPS-related TEAEs were low. Monitoring with EPS scales suggested no evidence of treatment-emergent akathisia or parkinsonism in these subjects who received long-term treatment with valbenazine.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/low-incidence-of-extrapyramidal-symptoms-in-subjects-with-tardive-dyskinesia-receiving-long-term-valbenazine-nbi-98854-treatment/