Impact of ND0612 on Levodopa-induced Dyskinesia in Parkinson’s Disease: Post-hoc Analyses from a Randomized, Active-controlled Study
Aaron Ellenbogen1, Rajesh Pahwa2, jorge hernandez-vara3, Nelson Lopes4, Alejandro Salah5, Alberto Espay6
1Quest Research Institute, 2University of Kansas Medical Center, 3Vall D,Hebron Hospital, 4NeuroDerm Ltd, 5Mitsubishi Tanabe Pharma America, 6James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, University of Cincinnati
Objective:
To evaluate dyskinesia-related outcomes between optimized subcutaneously administered levodopa/carbidopa (ND0612) + immediate-release levodopa/carbidopa (IR-LD/CD) vs optimized oral IR-LD/CD in patients with Parkinson’s disease (PD).
Background:
Investigational ND0612 is under development as a subcutaneous infusion for continuous levodopa delivery to supplement oral antiparkinsonian medications for PD patients with motor fluctuations. The pivotal trial showed that treatment with an optimized ND0612 + IR-LD/CD regimen significantly reduced motor fluctuations. Here we evaluated the impact of this treatment on levodopa-induced dyskinesia.
Design/Methods:
Levodopa-treated PD patients with motor fluctuations underwent an open-label, run-in phase to establish their optimal IR-LD/CD + ND0612 regimen. Participants were then randomized to a 12-week double-blind regimen of either optimized ND0612 + placebo IR-LD/CD or IR-LD/CD + placebo ND0612. Here we present post hoc analyses for the overall population and for the subgroup of patients with ≥1h troublesome dyskinesia at ND0612 initiation.
Results:
For the overall population, ND0612 decreased ON-time with non-troublesome dyskinesia (2.5h to 2.2h) and troublesome dyskinesia (0.7h to 0.5h), whereas they increased in IR-LD/CD–treated patients (from 2.4h to 2.6h and from 0.7h to 0.9h, respectively). There was a net gain of +2.1h with ND0612 vs IR-LD/CD in ON-time without any dyskinesia at the end of the double-blind period (p<0.0001). Participants with ≥1h troublesome dyskinesia showed a change [95% CI] in troublesome dyskinesia of −1.3h [−2.1, −0.5] with ND0612 (n=26) vs −0.05h [−0.9, 0.8] with IR-LD/CD (n=22), resulting in a net reduction of −1.2h [−2.4, −0.03] (p=0.046). Upon adjustment of medication in the conversion period, the incidence of dyskinesia was low and comparable in the 2 treatment arms (2% in each arm).
Conclusions:
Treatment with ND0612 plus supplemental IR-LD/CD decreased time with troublesome dyskinesia and increased ON-time without any dyskinesia.
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