CNSPulse
T112

VALIDATION OF THE NEUROKIT PLATFORM FOR CENTRAL NERVOUS SYSTEM PHARMACODYNAMIC ASSESSMENT IN HEALTHY VOLUNTEERS

Erin Tireman — Clay Dehn2, Vasileios Exadaktylos3, Janeen Rosales2, Lance Ballester1, Bailey Cox1, Alina Beaton1, Gabriel Jacobs3, William Martin1 1Lotus Clinical Research, 2Evolution Research Group, 3Centre for Human Drug Research

2026 ASCP Annual Meeting

Background

Quantifying pharmacodynamic (PD) effects of central nervous system (CNS) active compounds in early-phase clinical development requires sensitive and reproducible neurophysiological and neuropsychological assessments. The NeuroCart test battery has demonstrated the ability to quantify CNS drug effects across multiple functional domains but relies on specialized infrastructure that limits broader deployment. NeuroKit is a portable adaptation of NeuroCart designed to maintain sensitivity to CNS pharmacologic effects while enabling scalability across clinical research settings. This study is the second part in a two-part validation study that evaluates the reliability and external validity of NeuroKit when implemented at an independent US research site and compared against established data from the first in-house validation study. With the first study concluding validity against the NeuroCart, this second study aims to demonstrate reproducibility in an off-site setting.

Methods

This ongoing study is a randomized, double-blind, placebo-controlled, three-period crossover validation trial conducted in healthy adults aged 18 to 45 years at Clinical Pharmacology of Miami (CPMI). Sixteen participants receive single oral doses of lorazepam 2mg, modafinil 200mg, and placebo across three treatment periods, separated by 7-10 day washouts. NeuroKit assessments are performed at baseline and multiple post-dose timepoints aligned in time with those performed during the first part of the validation study at the Centre for Human Drug Research. The tests measure CNS PD effects across several domains, including saccadic eye movements (arousal), adaptive tracking (visuomotor coordination, sustained attention), finger tapping (fine motor performance; visuomotor coordination), smooth pursuit (visuomotor coordination), body sway (postural balance), N-back (working memory), VAS Bond and Lader and VAS Bowdle (subjective effects). CPMI data will be compared with reference results from the CHDR study using mixed-effects modeling to assess between-site reliability and equivalence of PD outcomes. All parameters will be logtransformed before analysis, to express the differences between the sites as ratios and estimate the 90% confidence interval (CI) around the ratio. The analysis will commence with the full model including the treatment, time, treatment by time, site (CPMI/CHDR), treatment by site, site by time and treatment by site by time as fixed factors, and participant, participant by treatment, and participant by time as random factors and the average baseline measurement per treatment period as covariate.

Results

Primary outcomes include NeuroKit-derived PD measures sensitive to sedation and stimulation, including saccadic reaction time, saccadic peak velocity, smooth pursuit performance, adaptive tracking accuracy, working memory performance, body sway, and psychomotor function. Analyses will evaluate effect sizes for drug-induced changes and assess whether PD responses observed at CPMI replicate previously characterized CNS effects of lorazepam and modafinil observed at CHDR.

Conclusions

This study aims to establish the reproducibility and external validity of the NeuroKit platform outside its development site. Demonstrating equivalence between CPMI and CHDR datasets would support the use of NeuroKit as a scalable tool for PD profiling of CNS-active compounds in early-phase clinical trials. Successful validation would enable broader availability of standardized CNS biomarker assessments, increase their application in clinical trials with patients and strengthen the translational assessment of novel therapeutics.