VANCOUVER—Once-daily treatment with 80 mg of valbenazine reduces tardive dyskinesia severity, according to research presented at the 68th Annual Meeting of the American Academy of Neurology. The drug appears to be well tolerated and raises no notable safety concerns.
Tardive dyskinesia is characterized by abnormal, involuntary movements of the tongue, lips, face, trunk, and limbs. The movement disorder occurs in patients with chronic exposure to dopamine-receptor blocking agents (eg, antipsychotics) and often persists after drug discontinuation. No FDA-approved medications for the treatment of tardive dyskinesia are available.
Robert A. Hauser, MD, Professor of Neurology, Molecular Pharmacology, and Physiology at the University of South Florida Morsani College of Medicine in Tampa, and colleagues conducted a randomized, double-blind, placebo-controlled phase III trial of valbenazine, a highly selective inhibitor of vesicular monoamine transporter type 2, for the treatment of tardive dyskinesia. Earlier studies had suggested the drug's safety and efficacy.
The investigators enrolled patients with schizophrenia, schizoaffective disorder, or mood disorders into the study. Participants had moderate or severe tardive dyskinesia and a DSM-IV diagnosis of neuroleptic-induced tardive dyskinesia for at least three months prior to screening. In all, 78 patients were randomized to placebo, 76 were randomized to 40 mg/day of valbenazine, and 80 were randomized to 80 mg/day of valbenazine. The treatment period lasted for six weeks, and participants underwent evaluations at week 2, week 4, and week 6.
The study's primary efficacy end point was change from baseline to week 6 on the Abnormal Involuntary Movement Scale (AIMS), as assessed by blinded central video raters. AIMS examinations were filmed, and scoring was performed by consensus of pairs of central raters who were blinded to treatment arm and study video sequence. The secondary efficacy end point was Clinical Global Impression of Change for Tardive Dyskinesia (CGI-TD) mean score at week 6, as assessed by site investigators.
The population's mean age was 56. About 54% of patients were male, and two-thirds of subjects had schizophrenia or schizoaffective disorder. The population's mean AIMS score at baseline was 10.1.
At week 6, AIMS score improved by 0.1 points, compared with baseline, for patients receiving placebo.
Participants receiving 80 mg/day of valbenazine had an improvement of 3.2 points, compared with baseline, and this result was highly statistically significant. In addition, patients receiving 40 mg/day of valbenazine had an improvement of 1.9 points, compared with baseline. The investigators observed a trend toward improvement in CGI-TD scores for patients receiving valbenazine.
The rates of adverse events were similar between groups. Treatment-emergent adverse events occurred in 45% of the placebo group, 39% of the valbenazine 40 mg group, and 49% of the valbenazine 80 mg group. The most common adverse event was somnolence. The rate of discontinuations due to adverse events was "strikingly low" and similar across groups, said Dr. Hauser. Three serious adverse events occurred in the placebo group, four in the valbenazine 40 mg group, and six in the 80 mg group. One patient receiving 80 mg/day of valbenazine died, and the site investigator and data safety monitoring board judged the event unlikely related to study medication. Participants' psychiatric status remained stable.
A second phase III study of valbenazine is currently under way, said Dr. Hauser. Given the observed dose response and the drug's tolerability, it would be worthwhile to investigate higher doses of valbenazine, he concluded.