Mesdopetam for the Treatment of Levodopa Induced Dyskinesia in Parkinson's Disease: A Randomized Phase 2b Trial.

IF 2.6 4区医学 Q2 CLINICAL NEUROLOGY

Movement Disorders Clinical Practice Pub Date : 2025-02-26 DOI:10.1002/mdc3.70004

Angelo Antonini, Padraig O'Suilleabhain, Fabricio Stocchi, Johanna Landström, Susanna Waters, Clas Sonesson, Joakim Tedroff

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Abstract

Background: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is a largely unmet need.

Objectives: Mesdopetam is a novel small molecule dopamine D3 receptor antagonist aimed for the treatment of levodopa-induced dyskinesia. This was a phase 2b study dose finding study to investigate efficacy and safety of 2.5 mg, 5 mg and 7,5 mg b.i.d. in a randomized controlled trial.

Methods: PD patients with ≥2 hours of troublesome dyskinesia were randomized to placebo or mesdopetam twice daily for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in ON time without troublesome dyskinesia (Good ON-time) as recorded with home diaries. Secondary efficacy endpoints assessing ON phase dyskinesia were the modified UDysRS (sum of parts 1, 3 and 4) and MDS-UPDRS part 4.2.

Results: Groups did not differ in change from baseline to end of study in Good ON-time. Several secondary assessments for ON phase dyskinesia such as the modified UDysRS showed clinically relevant and statistically significant improvements for the 2.5 and 7.5 mg doses. OFF time showed dose dependent decrease with highest efficacy for the 7.5 mg dose. The adverse event profile was similar to placebo.

Conclusions: In this study mesdopetam failed to increase Good ON-time as compared to placebo. However, a statistically significant and clinically meaningful improvement in the prespecified secondary efficacy endpoint UDysRS warrants further investigation. Results from this dose finding study suggest 7.5 mg b.i.d. to be the preferred dose for further study.

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治疗帕金森病左旋多巴诱发的运动障碍的美索培坦：随机 2b 期试验。

背景：治疗左旋多巴诱发的帕金森病（PD）运动障碍在很大程度上是一项尚未满足的需求：Mesdopetam 是一种新型小分子多巴胺 D3 受体拮抗剂，旨在治疗左旋多巴诱发的运动障碍。这是一项 2b 期剂量发现研究，旨在通过随机对照试验调查 2.5 毫克、5 毫克和 7,5 毫克剂量的疗效和安全性：方法：将运动障碍≥2小时的帕金森病患者随机分配到安慰剂或美司多培坦中，每天两次，为期12周。主要疗效终点是通过家庭日记记录的无运动障碍时间（良好的运动障碍时间）从基线到第 12 周的变化。评估 ON 期运动障碍的次要疗效终点是改良的 UDysRS（第 1、3 和 4 部分之和）和 MDS-UPDRS 第 4.2 部分：从基线到研究结束，各组在良好 ON 时间的变化上没有差异。对ON阶段运动障碍进行的几项次级评估（如改良的UDysRS）显示，2.5毫克和7.5毫克剂量的临床相关性和统计学上的显著改善。关机时间的缩短与剂量有关，7.5 毫克剂量的疗效最佳。不良反应情况与安慰剂相似：结论：在这项研究中，与安慰剂相比，美索培坦未能增加良好的开启时间。结论：在这项研究中，与安慰剂相比，美索培坦未能增加良好ON时间，但在预设的次要疗效终点UDysRS上有统计学意义和临床意义的改善，值得进一步研究。这项剂量发现研究的结果表明，7.5 毫克（b.i.d）是进一步研究的首选剂量。

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来源期刊

Movement Disorders Clinical Practice CLINICAL NEUROLOGY-

CiteScore

4.00

自引率

7.50%

发文量

218

期刊介绍： Movement Disorders Clinical Practice- is an online-only journal committed to publishing high quality peer reviewed articles related to clinical aspects of movement disorders which broadly include phenomenology (interesting case/case series/rarities), investigative (for e.g- genetics, imaging), translational (phenotype-genotype or other) and treatment aspects (clinical guidelines, diagnostic and treatment algorithms)