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Clinical Trial
. 2025 Jun;12(6):796-806.
doi: 10.1002/mdc3.70004. Epub 2025 Feb 26.

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

Angelo Antonini  1 , Padraig O'Suilleabhain  2 , Fabricio Stocchi  3 , Johanna Landström  4 , Susanna Waters  4 , Clas Sonesson  4 , Joakim Tedroff  4
Affiliations
Clinical Trial

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

Angelo Antonini et al. Mov Disord Clin Pract. 2025 Jun.

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.

Keywords: Parkinson's disease; dopamine D3; dyskinesia; mesdopetam.

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Figures

Figure 1
Figure 1
Subject disposition. Percentages are based on the number of randomized patients in the Safety Analysis Set. Reason for early withdrawal and period of withdrawal percentages are based on patients who withdrew from the study. Completed is defined as if patient finished Visit 5 (Week 12). Of the 39 subjects randomized to 7.5 mg only 38 received at least one dose of IMP.
Figure 2
Figure 2
Modified UDysRS (sum of parts 1, 3, 4) score change from baseline over time for the FAS, randomized doses, left panel, and daily OFF‐time (h) change from baseline over time for the FAS, randomized doses, right panel. Shown are LS means ± SE derived from the MMRM model. *P < 0.05, **P < 0.01 vs. placebo.
See this image and copyright information in PMC

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