Session Information
Date: Saturday, October 6, 2018
Session Title: Clinical Trials and Therapy in Movement Disorders
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To study the pharmacodynamics (PD) of CX-8998, using pharmaco-electroencephalography (phEEG) and define plasma concentrations of CX-8998 which are pharmacologically active on objective CNS parameters.
Background: PhEEG concerns the description and the quantitative analysis of the effects of substances on the CNS by means of electrophysiological methods. PhEEG has demonstrated its value in the development of CNS-active compounds in many instances, and is recognized as a PD marker to study the effects of drugs on brain functions in patients and healthy volunteers.
Methods: A randomized, double-blind, placebo-controlled, 3-period crossover study to evaluate the PD effects of single oral doses of CX-8998 in 12 healthy young male subjects. In each treatment period, each subject received single oral doses of Treatment A (CX-8998 5 mg), Treatment B (CX-8998 18 mg) or Treatment C (placebo). Endpoints in this analysis were the alpha, beta, gamma, delta and theta frequency band power in the awake state, in the eyes closed condition, post CX-8998 (5 and 18 mg) and placebo administration, measured at 1 and 3 hours post dose. EEG data from the electrode sites were scored by blinded personnel.
Results: Analysis of awake phEEG revealed statistically significant, dose-dependent changes in EEG power density spectra in the alpha frequency band. PK/PD analyses suggest that reductions of alpha power of about 25% or greater occur in a concentration-dependent manner at plasma CX-8998 concentrations greater than 200 to 300 nM. The maximal reduction in alpha band power was observed at plasma CX-8998 concentrations of approximately 700-800 nM and greater.
Conclusions: These data suggest that plasma concentrations in approximately the 200-800 nM range have CNS activity and may provide therapeutic efficacy and are used for dose setting in ongoing and planned clinical trials with CX-8998.
To cite this abstract in AMA style:
S. Papapetropoulos, M. Lee, S. Boyer. Proof-of-Principle Quantitative EEG Study of CX-8998, an Oral, Potent and Selective T-Type Calcium antagonist in development for symptomatic treatment of Essential Tremor and Parkinson’s disease Tremor [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/proof-of-principle-quantitative-eeg-study-of-cx-8998-an-oral-potent-and-selective-t-type-calcium-antagonist-in-development-for-symptomatic-treatment-of-essential-tremor-and-parkinsons-disease-trem/. Accessed May 24, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/proof-of-principle-quantitative-eeg-study-of-cx-8998-an-oral-potent-and-selective-t-type-calcium-antagonist-in-development-for-symptomatic-treatment-of-essential-tremor-and-parkinsons-disease-trem/