Deutetrabenazine治疗患者的不自主运动的迟发性运动障碍(AIM-TD):一项双盲,随机,安慰剂对照,3期临床试验。

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斯塔姆勒安德森KE, D,戴维斯博士因素SA,豪泽RA, Isojarvi J, Jarskog低频,Jimenez-Shahed J, Kumar R, McEvoy JP, Ochudlo年代,帕斯WG,费尔南德斯HH

Deutetrabenazine治疗患者的不自主运动的迟发性运动障碍(AIM-TD):一项双盲,随机,安慰剂对照,3期临床试验。

柳叶刀神经病学杂志上。2017年8月,4 (8):595 - 604。doi: 10.1016 / s2215 - 0366 (17) 30236 - 5。Epub 2017年6月28日。

PubMed ID
28668671 (在PubMed
]
文摘

背景:迟发性运动障碍的结果多巴胺受体拮抗剂,如典型和非典型抗精神病药物。如果临床上合适,临床医生经常管理这个障碍通过降低剂量,或中断,致病药物。是一个重大的未满足的需要一个治疗方案,不破坏潜在精神疾病的治疗方案。我们旨在评估的有效性、安全性和耐受性的固定剂量的deutetrabenazine-a小说水泡单胺transporter-2抑制剂在迟发性运动障碍患者。方法:我们这样做双盲,随机,安慰剂对照,3期临床试验在75中心在美国和欧洲。18 - 80岁的迟发性运动障碍的患者(> / = 3个月前筛查)被随机分配集中(1:1:1:1),通过互动响应技术,得到三种固定剂量的deutetrabenazine(12毫克/天,24毫克/天,或36毫克/天)或匹配的安慰剂。随机分层了基线多巴胺受体拮抗剂的使用。患者开始口服deutetrabenazine 12毫克/天,这个剂量增加到星期4直到实现随机剂量,然后保持在8周。在治疗期间,患者,调查人员,他们的网站人员,和赞助商蒙面组分配。主要疗效终点是异常变化非随意运动规模(目标)的分数从基线到第12周的患者至少有一个post-baseline评级。 The primary efficacy analysis was done in the modified intention-to-treat population (baseline AIMS score >/=6 and at least one post-baseline rating). The safety analysis was done in patients who received any study drug. This trial is registered with ClinicalTrials.gov, number NCT02291861. FINDINGS: Between Oct 29, 2014, and Aug 19, 2016, we randomly assigned 298 patients to receive at least one dose of placebo (n=74), deutetrabenazine 12 mg/day (n=75), 24 mg/day (n=74), or 36 mg/day (n=75); 222 patients comprised the modified intention-to-treat population and 293 patients comprised the safety population. From baseline to week 12, the least-squares mean AIMS score improved by -3.3 points (SE 0.42) in the deutetrabenazine 36 mg/day group, -3.2 points (0.45) in the 24 mg/day group, and -2.1 points (0.42) in the 12 mg/day group, with a treatment difference of -1.9 points (SE 0.58, 95% CI -3.09 to -0.79; p=0.001), -1.8 points (0.60, -3.00 to -0.63; p=0.003), and -0.7 points (0.57, -1.84 to 0.42; p=0.217), respectively, versus -1.4 points (0.41) in the placebo group. The rate of adverse events was similar between patients in the deutetrabenazine 36 mg/day group (n=38/74 [51%]), 24 mg/day group (n=32/73 [44%]), and 12 mg/day group (n=36/74 [49%]), and those in the placebo group (n=34/72 [47%]). Serious adverse events were reported in four (5%) patients given deutetrabenazine 36 mg/day, six (8%) patients given 24 mg/day, and two (3%) patients given 12 mg/day, compared with four (6%) patients given placebo. Two (1%) patients in the safety population died, one each in the deutetrabenazine 24 mg/day and 36 mg/day groups; neither death was deemed related to study drug by the investigator or sponsor. INTERPRETATION: Deutetrabenazine 24 mg/day and 36 mg/day provided a significant reduction in tardive dyskinesia, with favourable safety and tolerability. These findings suggest that dosing regimens could be individualised and tailored for patients on the basis of dyskinesia control and tolerability. FUNDING: Teva Pharmaceutical Industries.

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