A Phase 3, 1-Year, Open-Label Trial of Valbenazine in Adults With Tardive Dyskinesia

作者：Stephen R. Marder, Carlos Singer, Jean‐Pierre Lindenmayer, Caroline M. Tanner, Cynthia L. Comella, Cherian Verghese, Roland Jimenez, Grace Liang, Joshua Burke, Christopher O’Brien · 发表于：Journal of Clinical Psychopharmacology · 年份：2019 · DOI：10.1097/jcp.0000000000001111 · 被引用次数：33 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Botulinum Toxin and Related Neurological Disorders、Neurogenetic and Muscular Disorders Research

PURPOSE/BACKGROUND: Valbenazine is approved to treat tardive dyskinesia (TD) in adults. KINECT 4 (NCT02405091) was conducted to explore the long-term effects of once-daily valbenazine in patients with TD. METHODS/PROCEDURES: The study included a 48-week, open-label treatment period and 4-week washout. Dosing was initiated at 40 mg/d, with escalation to 80 mg/d at week 4 based on efficacy and tolerability. Standard safety methods were applied, including treatment-emergent adverse event (TEAE) reporting. Valbenazine effects on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD, and Patient Global Impression of Change. FINDINGS/RESULTS: After week 4, <15% of all participants had a serious TEAE (13.7%) or TEAE leading to discontinuation (11.8%). Participants experienced TD improvements during long-term treatment as indicated by mean change from baseline to week 48 in AIMS total score (sum of items 1-7, evaluated by site raters) with valbenazine 40 mg/d (-10.2 [n = 45]) or 80 mg/d (-11.0 [n = 107]). At week 48, most participants had ≥50% improvement from baseline in AIMS total score (40 mg/d, 90.0%; 80 mg/d, 89.2%), Clinical Global Impression of Change-TD rating of much or very much improved (40 mg/d, 90.0%; 80 mg/d, 95.9%), and Patient Global Impression of Change rating of much or very much improved (40 mg/d, 90.0%; 80 mg/d, 89.2%). No dose effects were apparent by week 36. Week 52 results indicated some loss of effect a...