清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial

卡比多巴 左旋多巴 帕金森病 医学 养生 麻醉 物理疗法 疾病 外科 内科学 安慰剂 替代医学 病理
作者
Alberto J. Espay,Fabrizio Stocchi,Rajesh Pahwa,Alberto Albanese,Aaron Ellenbogen,Joaquim J. Ferreira,Nir Giladi,Tanya Gurevich,Sharon Hassin‐Baer,Jorge Hernández‐Vara,Stuart Isaacson,Karl Kieburtz,Peter A. LeWitt,Lydia López Manzanares,C. Warren Olanow,Werner Poewe,Harini Sarva,Tami Yardeni,Liat Adar,Laurence Salin
出处
期刊:Lancet Neurology [Elsevier BV]
卷期号:23 (5): 465-476 被引量:28
标识
DOI:10.1016/s1474-4422(24)00052-8
摘要

Background Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa–carbidopa solution) compared with oral immediate-release levodopa–carbidopa for the treatment of motor fluctuations in people with Parkinson's disease. Methods We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson's disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa–carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa–carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa–carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa–carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT04006210, and is complete. Findings Between Sept 30, 2019, and April 8, 2022, 381 participants were enrolled, of whom 259 (68%) were randomly assigned, 128 (49%) to subcutaneous ND0612 and 131 (51%) to oral levodopa–carbidopa. 243 (94%) participants completed the study. Treatment with subcutaneous ND0612 provided an additional 1·72 h (95% CI 1·08 to 2·36) of on time without troublesome dyskinesia compared with oral levodopa–carbidopa (change from baseline of –0·48 h [–0·94 to –0·02] with subcutaneous ND0612 vs –2·20 h [–2·65 to –1·74] with oral levodopa–carbidopa; p<0·0001). Significant treatment differences favouring subcutaneous ND0612 were also found in the first four of nine prespecified hierarchical outcomes of daily off time (–1·40 h [95% CI –1·99 to –0·80]), Movement Disorders Society-Unified Parkinson's Disease Rating Scale part II scores (–3·05 [–4·28 to –1·81]), Patients Global Impression of Change (odds ratio [OR] 5·31 [2·67 to 10·58]), and Clinical Global Impression of Improvement (OR 7·23 [3·57 to 14·64]). Hierarchical testing ended after the fourth secondary endpoint. Adverse events were reported by 287 (89%) of 322 participants during open-label ND0612 optimisation, and by 103 (80%) of 128 in the ND0612 group and 97 (74%) of 131 in the oral levodopa–carbidopa group during the double-blind phase. The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group vs 56 [43%] in the oral levodopa–carbidopa group during the double-blind phase), most of which were mild. Serious adverse events in four participants in the ND0612 group were related to study treatment (infusion-site cellulitis [n=2], infusion-site abscess and infusion-site ulcer [n=1]; and paraesthesia and peripheral sensorimotor neuropathy [n=1]). One participant in the ND0612 group died during the double-blind phase, but the death was not related to study treatment (fall leading to traumatic brain injury). Interpretation Results of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa–carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit–risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment. Funding NeuroDerm.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
研究水合物的小白完成签到 ,获得积分10
5秒前
6秒前
zhao完成签到,获得积分10
8秒前
嗯嗯嗯哦哦哦完成签到 ,获得积分10
10秒前
李大宝完成签到 ,获得积分10
10秒前
lilylwy完成签到 ,获得积分0
13秒前
fy发布了新的文献求助10
13秒前
Horizon完成签到 ,获得积分10
13秒前
Kevin发布了新的文献求助30
17秒前
tengyi完成签到 ,获得积分10
30秒前
无敌幸运儿完成签到 ,获得积分10
30秒前
xiaobin完成签到 ,获得积分10
30秒前
gengsumin完成签到,获得积分10
33秒前
美含完成签到 ,获得积分10
47秒前
西瓜完成签到 ,获得积分10
53秒前
55秒前
路过完成签到 ,获得积分10
1分钟前
喜悦的香之完成签到 ,获得积分10
1分钟前
文静元霜完成签到 ,获得积分10
1分钟前
甜乎贝贝完成签到 ,获得积分10
1分钟前
1分钟前
科研通AI5应助威武鸵鸟采纳,获得30
1分钟前
酷酷阑香发布了新的文献求助10
1分钟前
John完成签到 ,获得积分10
1分钟前
心想事成完成签到 ,获得积分10
1分钟前
机灵的幻灵完成签到 ,获得积分10
1分钟前
嘟嘟52edm完成签到 ,获得积分10
1分钟前
看不见的美完成签到 ,获得积分10
1分钟前
byron完成签到 ,获得积分10
1分钟前
ww完成签到,获得积分10
1分钟前
SC完成签到 ,获得积分10
1分钟前
SCI完成签到 ,获得积分10
1分钟前
1分钟前
rora完成签到 ,获得积分10
1分钟前
颜色渐变完成签到 ,获得积分10
1分钟前
2分钟前
2分钟前
stiger完成签到,获得积分10
2分钟前
现代大神完成签到,获得积分10
2分钟前
正直的松鼠完成签到 ,获得积分10
2分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968559
求助须知:如何正确求助?哪些是违规求助? 3513358
关于积分的说明 11167340
捐赠科研通 3248714
什么是DOI,文献DOI怎么找? 1794453
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804664