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

BACKGROUND: 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.