2025 American Academy of Neurology Abstract Website

Aaron L. Ellenbogen¹, Alberto J. Espay², Robert A. Hauser³, Fabrizio Stocchi⁴, Rajesh Pahwa⁵, Joaquim J. Ferreira⁶, Karl Kieburtz⁷, Alberto Albanese⁸, Nir Giladi⁹, Laurence Salin¹⁰, Nissim Sasson¹⁰, Liat Adar¹⁰, Natalia Vostokova¹⁰, Jonathan Pereira¹¹, Olivier Rascol¹²
¹Quest Research Institute, ²James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, ³University of South Florida, ⁴University San Raffaele Roma and Institute for Research and Medical Care IRCCS San Raffaele, ⁵University of Kansas Medical Center, ⁶Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, ⁷Clintrex Research Corp, ⁸Department of Neurology, IRCCS Istituto Clinico Humanitas, ⁹Brain Institute, Tel-Aviv Medical Center Faculty of Medicine, Sagol School of Neurosciences, Tel Aviv University, ¹⁰NeuroDerm Ltd., ¹¹Mitsubishi Tanabe Pharma America, Inc., ¹²University of Toulouse 3, University Hospital of Toulouse, INSERM, Clinical Investigation Center CIC1436

Objective:

To evaluate the effect of investigational ND0612 on PD motor state characteristics in patients with PD experiencing motor fluctuations from the BouNDless (NCT04006210) study.

Background:

Primary efficacy analysis demonstrated superiority of ND0612 over immediate-release levodopa/carbidopa (IR-LD/CD), with a difference of 1.72h (p<0.0001) in Good ON-time.

Design/Methods:

We performed post hoc analysis of diary data and descriptively analyzed the number and duration of episodes spent in each PD motor state. The total number of transitions between any motor state were analyzed by baseline-adjusted Poisson Regression. Patients who completed the double-blind phase of the study were eligible to enter into the ND0612 OLE (up to 54 months). Changes in diary states (from ND0612 initiation in the run-in phase) were normalized to 16h and analyzed using mixed model repeated measures without imputation.

Results:

At the end of the double-blind phase, patients in the ND0612 vs IR-LD/CD group experienced an average of 2.4 vs 3.3 OFF episodes per day, with a total daily OFF-duration of 3.8h vs 5.2h. Participants (ND0612 vs IR-LD/CD) experienced 2.7 vs 3.1 episodes of ON without dyskinesia (total duration of 9.4h vs 7.4h); 1.2 vs 1.4 episodes of ON with non-troublesome dyskinesia (total duration of 2.2h vs 2.7h); and 0.3 vs 0.5 episodes of ON with troublesome dyskinesia (total duration of 0.4h vs 0.7h). The mean number of daily transitions between motor states (ND0612 vs IR-LD/CD) was 5.3 vs 7.1 (p<0.0001). Most (167/232; 72%) participants who entered the OLE, completed 1 year of ND0612 treatment. Efficacy benefits were sustained at Month 12 with a change of –1.86±0.18h in OFF-time (P<0.0001), +1.96±0.18h in Good ON-time, and +2.19±0.26h in ON-time without any dyskinesia. The ND0612 regimen was generally safe and well-tolerated.

Conclusions:

Treatment with ND0612, versus IR-LD/CD, led to more stable motor control in patients with PD and motor fluctuations.