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Clinical Trial
. 2025 Jun;40(6):1134-1142.
doi: 10.1002/mds.30175. Epub 2025 Mar 17.

NLX-112 Randomized Phase 2A Trial: Safety, Tolerability, Anti-Dyskinetic, and Anti-Parkinsonian Efficacy

Per Svenningsson  1 , Per Odin  2 , Filip Bergquist  3   4 , Karin Wirdefeldt  5 , Dag Nyholm  6 , Mattias Andréasson  1 , Ioanna Markaki  1 , Anders C Johansson  5 , Måns Jergil  7 , Christopher Jankosky  8 , Mark A Varney  8 , Fabienne Herbrecht  9 , Steven A Johnson  8 , Adrian Newman-Tancredi  9
Affiliations
Clinical Trial

NLX-112 Randomized Phase 2A Trial: Safety, Tolerability, Anti-Dyskinetic, and Anti-Parkinsonian Efficacy

Per Svenningsson et al. Mov Disord. 2025 Jun.

Abstract

Background: Levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is associated with 'false neurotransmitter' release of dopamine from serotonin (5-HT) neurons. NLX-112 is a first-in-class, highly selective 5-HT1A receptor agonist which counteracts LIDs in experimental PD models.

Objectives: The primary objective was to evaluate the safety and tolerability of NLX-112 compared with placebo in people with PD. The secondary objective was to assess the preliminary efficacy of NLX-112 in reducing LID and its effects on PD symptoms.

Methods: Participants received NLX-112 or placebo (2:1 ratio) alongside stable Parkinson's medications, with 22 participants completing the study. Dosing was up-titrated over 28 days to 2 mg/day (1 mg twice daily), stabilized for 14 days (to day 42), and down-titrated for 14 days. Efficacy was measured using the Unified Dyskinesia Rating Scale (UDysRS), Unified Parkinson's Disease Rating Scale (UPDRS), and Clinical Global Impression of Change (CGI-C) following a levodopa challenge (150% of usual dose).

Results: Adverse events (AEs) were mainly central nervous system (CNS)-related and mostly occurred during up-titration, with no serious AEs in the NLX-112 group. There were no treatment-induced clinically significant changes in vital signs, electrocardiogram, or laboratory parameters. NLX-112 reduced LID from baseline levels: at day 42, UDysRS total score decreased by 6.3 points, whereas placebo group changes were not significant (-2.4). NLX-112 also reduced parkinsonism from baseline values: UPDRS Part 3 scores decreased by 3.7 points, whereas placebo group changes were non-significant (+0.1). In CGI-C assessment, the NLX-112 group showed greater improvement than the placebo group (53% vs. 29%).

Conclusion: These results support further clinical investigation of NLX-112 for treatment of PD LID. © 2025 Neurolixis SAS. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: 5‐HT1A receptor; NLX‐112; Parkinson's disease; dyskinesia; levodopa; serotonin.

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Figures

Figure 1
Figure 1
Subject disposition. DBS, deep brain stimulation.
See this image and copyright information in PMC

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