Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study.
Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study.
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DOI：
10.1212/wnl.0000000000005010
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发表时间：
2018-02-20
期刊：
影响因子：
9.9
通讯作者：
Kosaka K
中科院分区：
文献类型：
--
作者：
Murata M;Odawara T;Hasegawa K;Iiyama S;Nakamura M;Tagawa M;Kosaka K
研究唑尼沙胺作为左旋多巴辅助治疗路易体痴呆（DLB）患者帕金森病的疗效和安全性。这项 2 期安慰剂对照、随机、双盲研究包括磨合期（安慰剂，4 周）和治疗期（安慰剂或唑尼沙胺 25 或 50 mg，每天一次，12 周）期。诊断为可能患有 DLB 的门诊患者有资格纳入。主要终点是第 12 周时统一帕金森病评定量表 (UPDRS) 第 3 部分总分相对于基线的变化。还评估了认知功能、痴呆症行为和心理症状 (BPSD)、护理人员负担、作为次要终点的其他 UPDRS 部分以及安全性。总体而言，158 名 DLB 患者接受了研究药物； 21 人在治疗期间中断，137 人完成治疗。与安慰剂相比，唑尼沙胺 50 mg 组在第 12 周时 UPDRS 第 3 部分总分的改善显着更大（组间差异 -4.1；95% 置信区间 -6.8 至 -1.4；p = 0.003）。唑尼沙胺不会加重认知功能、BPSD 或照护者负担。唑尼沙胺 50 mg 组的总体不良事件发生率高于 25 mg 组和安慰剂组（分别为 65.3%、43.1% 和 50.0%）；所有组中观察到的严重不良事件发生率相似。唑尼沙胺（左旋多巴的辅助药物）可改善伴有 DLB 的帕金森病，且不会恶化认知功能或精神症状。 JapicCTI-122040。这项研究提供了 I 类证据，证明唑尼沙胺（左旋多巴的辅助药物）可改善帕金森病，并且对 DLB 患者具有良好的耐受性。
To investigate the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with dementia with Lewy bodies (DLB). This phase 2, placebo-controlled, randomized, double-blind study consisted of run-in (placebo, 4 weeks) and treatment (placebo or zonisamide 25 or 50 mg once daily, 12 weeks) periods. Outpatients diagnosed with probable DLB were eligible for inclusion. The primary endpoint was the change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) part 3 total score at week 12. Cognitive function, behavioral and psychological symptoms of dementia (BPSD), caregiver burden, other UPDRS parts as secondary endpoints, and safety were also assessed. Overall, 158 patients with DLB received the study drug; 21 discontinued during treatment and 137 completed treatment. Improvement in UPDRS part 3 total score at week 12 was significantly greater in the zonisamide 50 mg group compared with placebo (between-group difference −4.1; 95% confidence interval −6.8 to −1.4; p = 0.003). Zonisamide did not worsen cognitive function, BPSD, or caregiver burden. The overall incidence of adverse events was higher in the zonisamide 50 mg than the 25 mg and placebo groups (65.3%, 43.1%, and 50.0%, respectively); similar rates of serious adverse events were observed among all groups. Zonisamide (adjunctive to levodopa) improved parkinsonism accompanying DLB without worsening cognitive function or psychiatric symptoms. JapicCTI-122040. This study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well-tolerated in patients with DLB.