The effects of valbenazine on tardive dyskinesia in older and younger patients

Abstract

Objective: To evaluate the effects of once-daily valbenazine (40 or 80 mg/d) in older and younger adults with tardive dyskinesia (TD).

Methods: Data were pooled from three 6-week, randomized, double-blind, placebo-controlled (DBPC) studies (KINECT [NCT01688037], KINECT 2 [NCT01733121], and KINECT 3 [NCT02274558]) and two long-term studies (KINECT 3 extension and KINECT 4 [NCT02405091]). Outcomes analyzed in older and younger participants (55 years or older and younger than 55 years, respectively) included Abnormal Involuntary Movement Scale (AIMS) response (threshold of greater than or equal to 50% improvement from baseline in total score [items 1 to 7]) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) response (score 2 or less ["very much improved" or "much improved"]). Safety assessments included treatment-emergent adverse events (TEAEs).

Results: At week 6 (end of DBPC treatment), the percentage of participants who met the AIMS response threshold was higher with valbenazine versus placebo in both subgroups: 55 years or older (80 mg/d, 39.7% [P < .001]; 40 mg/d, 28.6% [P < .01]; placebo, 9.7%); younger than 55 years (80 mg/d, 39.5% [P < .001]; 40 mg/d, 20.0% [P > .05]; placebo, 10.8%). The percentage of participants with CGI-TD response was also higher with valbenazine versus placebo: 55 years or older (80 mg/d, 41.3% [P < .01]; 40 mg/d, 30.2% [P > .05]; placebo, 19.4%); younger than 55 years (80 mg/d, 39.5% [P < .05]; 40 mg/d, 35.3% [P < .05]; placebo, 18.5%). Responses at week 48 (end of long-term treatment, combined doses) were as follows: 55 years or older (AIMS, 70.7%; CGI-TD, 82.8%); younger than 55 years (AIMS, 58.7%; CGI-TD, 72.3%). No significant differences between older and younger subgroups were found for AIMS or CGI-TD response. No new safety signals or TEAEs of clinical concern were found in older participants who received long-term treatment.

Conclusions: Valbenazine improved TD and was generally well tolerated in older and younger adults.

Keywords: age; clinical trial; efficacy; older adults; safety; tardive dyskinesia; tolerability; valbenazine.

Conflict of interest statement

Dr Sajatovic has received research support from the National Institutes of Health, Centers for Disease Control and Prevention, Janssen, Merck, Pfizer, Reinberger Foundation, Reuter Foundation, Alkermes, Otsuka, and the Woodruff Foundation; has been a consultant for Bracket, Neurocrine Biosciences, Inc, Otsuka, Pfizer, ProPhase, LLC, Health Analytics, and Supernus Pharmaceuticals; has received royalties from Johns Hopkins University Press, Lexicomp, Oxford University Press, Springer Press, and UpToDate; and has participated in continuing medical education activities for the American Physician Institute, CMEology, and MCM Education. Over the past 3 years, Dr Alexopoulos has served on the speakers' bureau for Takeda, Lundbeck, Otsuka, Allergan, and Sunovion. Mr. Burke, Dr Farahmand, and Dr Siegert are full‐time employees of Neurocrine Biosciences, Inc and are shareholders in the company.

© 2019 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Figures

Figure 1

AIMS improvements by study visit: based on (A) mean change from baseline in AIMS total score and (B) percentage of participants with greater than or equal to 50% improvement in AIMS total score. Outcomes analyzed at week 6 in the pooled DBPC population (based on central‐rater scoring only) and at weeks 48 and 52 in the pooled long‐term population (based on central‐rater scoring for KINECT 3 and site‐rater scoring for KINECT 4), based on observed cases. Least squares means presented for week 6; means presented for weeks 48 and 52. *P < .05; **P < .01; ***P < .001 versus placebo. AIMS, Abnormal Involuntary Movement Scale; d, Cohen's effect size; DBPC, double‐blind placebo‐controlled; NNT, number needed to treat; LT, long term; SE, standard error

Figure 2

CGI‐TD improvements by study visit: based on (A) CGI‐TD mean scores and (B) percentage of participants with a CGI‐TD score 2 or less. Analyzed at week 6 in the pooled DBPC population and at weeks 48 and 52 in the pooled long‐term population, based on observed cases. Least squares means presented for week 6; means presented for weeks 48 and 52. *P < .05; **P < .01 versus placebo. §P < .05 versus younger subgroup. CGI‐TD, Clinical Global Impression of Change—Tardive Dyskinesia; d, Cohen's effect size; DBPC, double‐blind, placebo‐controlled; LT, long term; NNT, number needed to treat; SE, standard error