当前位置: X-MOL 学术CNS Spectr. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of Deutetrabenazine on Metabolic Parameters in the Treatment of Tardive Dyskinesia
CNS Spectrums ( IF 3.4 ) Pub Date : 2021-05-10 , DOI: 10.1017/s1092852920002564
Joohi Jimenez-Shahed 1 , Hadas Barkay 2 , Karen E Anderson 3 , Hubert H Fernandez 4 , Stewart A Factor 5 , Robert A Hauser 6 , Maria Wieman 7 , Mark Forrest Gordon 7 , Juha-Matti Savola 8
Affiliation  

BackgroundDeutetrabenazine, a novel vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. Dopamine-receptor antagonists (DRAs) are associated with worsening of metabolic parameters, including weight gain, hyperlipidemia, and elevated blood glucose. This post hoc analysis assessed the short- and long-term effects of deutetrabenazine treatment on weight and metabolic parameters in individuals treated for TD.MethodsTwo 12-week, randomized placebo-controlled trials (RCTs) of deutetrabenazine for patients with TD evaluated either fixed dosing (AIM-TD; 12, 24, or 36 mg) or dose titration (ARM-TD; max dose, 48 mg/day). Patients completing ARM-TD or AIM-TD were included in an open-label extension (OLE) study, in which all patients underwent response-driven titration of deutetrabenazine from 12 mg/day up to a maximum total dose of 48 mg/day. Weight, body mass index (BMI), serum glucose, serum total cholesterol, and serum triglycerides were evaluated at baseline and during treatment in the RCTs and in the OLE.ResultsIn the RCTs, 282 and 133 patients received deutetrabenazine or placebo. At baseline, 77% of patients used DRAs. At Week 12, no meaningful changes in weight were observed, with mean (standard error) weight changes of 0.9–1.2 (0.3–0.5) and 0.2 (0.3) kg in the deutetrabenazine and placebo groups, respectively, and mean BMI changes of 0.3–0.5 (0.1–0.2) and 0.1 (0.1) kg/m2. 337 patients were included in the analysis of the OLE study. No meaningful changes were observed in weight (mean change: 0.4 [0.4] kg at Week 54, –0.5 [0.6] kg at Week 106, and –1.1 [0.6] kg at Week 145) or BMI (mean change: 0.1 [0.2] kg/m2 at Week 54, –0.2 [0.2] kg/m2 at Week 106, and –0.3 [0.2] kg/m2 at Week 145). Across the studies, no meaningful changes were observed in triglyceride, cholesterol, or glucose levels.ConclusionDeutetrabenazine does not affect common metabolic parameters in patients with TD, even during long-term exposure.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

中文翻译:

氘代丁苯那嗪治疗迟发性运动障碍对代谢参数的影响

背景 Deutetrabenazine 是一种新型囊泡单胺转运蛋白 2 (VMAT2) 抑制剂,已被 FDA 批准用于治疗成人迟发性运动障碍 (TD)。多巴胺受体拮抗剂 (DRA) 与代谢参数的恶化有关,包括体重增加、高脂血症和血糖升高。这项事后分析评估了去丁苯那嗪治疗对接受 TD 治疗的个体的体重和代谢参数的短期和长期影响。 (AIM-TD;12、24 或 36 mg)或剂量滴定(ARM-TD;最大剂量,48 mg/天)。完成 ARM-TD 或 AIM-TD 的患者被纳入开放标签扩展 (OLE) 研究,其中所有患者都接受了由反应驱动的去丁苯那嗪从 12 毫克/天至最大总剂量 48 毫克/天的滴定。在 RCT 和 OLE 中,在基线和治疗期间评估了体重、体重指数 (BMI)、血清葡萄糖、血清总胆固醇和血清甘油三酯。结果在 RCT 中,282 和 133 名患者接受了去丁苯那嗪或安慰剂治疗。基线时,77% 的患者使用 DRA。在第 12 周,没有观察到体重的有意义变化,去丁苯那嗪组和安慰剂组的平均(标准误差)体重变化分别为 0.9-1.2 (0.3-0.5) 和 0.2 (0.3) kg,平均 BMI 变化为 0.3 –0.5 (0.1–0.2) 和 0.1 (0.1) kg/m 在 RCT 和 OLE 中,在基线和治疗期间对血清甘油三酯进行了评估。结果在 RCT 中,282 和 133 名患者接受了去丁苯那嗪或安慰剂治疗。基线时,77% 的患者使用 DRA。在第 12 周,没有观察到体重的有意义变化,去丁苯那嗪组和安慰剂组的平均(标准误差)体重变化分别为 0.9-1.2 (0.3-0.5) 和 0.2 (0.3) kg,平均 BMI 变化为 0.3 –0.5 (0.1–0.2) 和 0.1 (0.1) kg/m 在 RCT 和 OLE 中,在基线和治疗期间对血清甘油三酯进行了评估。结果在 RCT 中,282 和 133 名患者接受了去丁苯那嗪或安慰剂治疗。基线时,77% 的患者使用 DRA。在第 12 周,没有观察到体重的有意义变化,去丁苯那嗪组和安慰剂组的平均(标准误差)体重变化分别为 0.9-1.2 (0.3-0.5) 和 0.2 (0.3) kg,平均 BMI 变化为 0.3 –0.5 (0.1–0.2) 和 0.1 (0.1) kg/m2. 337 名患者被纳入 OLE 研究的分析。体重(平均变化:第 54 周时为 0.4 [0.4] kg,第 106 周时为 –0.5 [0.6] kg,第 145 周时为 –1.1 [0.6] kg)或 BMI(平均变化:0.1 [0.2] ] 公斤/米2在第 54 周,–0.2 [0.2] kg/m2在第 106 周,和 –0.3 [0.2] kg/m2在第 145 周)。在所有研究中,没有观察到甘油三酯、胆固醇或葡萄糖水平发生有意义的变化。结论去丁苯那嗪不会影响 TD 患者的常见代谢参数,即使在长期暴露期间也是如此。资助Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
更新日期:2021-05-10
down
wechat
bug