Objective: To compare the effect of intravenous (DIZ101) and subcutaneous (DIZ102) continuous 16h infusion of a continuously buffered acidic levodopa/carbidopa solution with levodopa/carbidopa intestinal gel (LCIG) regarding motor symptoms in patients with advanced Parkinson’s disease (PD).

Background: LCIG is effictive for treating motor fluctuations in PD. Pharmacokinetic data indicate that stable blood concentrations of levodopa, equivalent with those following LCIG, can be achieved with DIZ101 and DIZ102. The carbidopa (CD) concentration is however four times higher than with LCIG [1]. The hypothesis that high blood concentrations of CD could reduce treatment efficacy by inhibiting CNS conversion of levodopa to dopamine can be tested by comparing the efficacy of DIZ101 and DIZ102 with that of LCIG.

Method: DIZ101, DIZ102 and LCIG were compared in a randomized, 3-period crossover, open-label, multicenter trial where 18 patients with PD completed all 16h treatments. The effects of treatments on motor symptoms were blindedly assessed before and during infusion by repeated UPDRS, dyskinesia and Treatment Response Scale (TRS) video rating of a subset of UPDRS III items and by concurrent accelerometry recordings with the Parkinson Kinetigraph (PKG) over 24h. The pharmacokinetic data have been reported previously [1].

Results: After 1.5h of infusion, mean (SEM) UPDRS scores were reduced by 2.6 (0.9) points with DIZ101 (p=0.007), 3.3 (0.8) points with DIZ102 (p<0.001) and 2.5 (0.7) points with LCIG (p=0.001). Despite higher carbidopa concentrations with DIZ101 and DIZ102¹, there were no differences in motor examination ratings with respect to UPDRS, dyskinesia or TRS between DIZ101, DIZ102 and LCIG at assessed time points (1.5h, 5h, 6h, 7h and 14h). The median PKG bradykinesia (BK) and dyskinesia (DK) scores also improved rapidly after treatment onset and did not differ between treatments in the predefined periods of infusion (0-2h, 2-8h, 8-16h).

Conclusion: There was no observable trend for lower levodopa efficacy on motor symptoms, despite the higher CD concentrations with DIZ101 and DIZ102 compared to LCIG [1]. This indicates, in line with previous reports [2][3], that high blood levels (up to approximately 800 ng/mL) of carbidopa do not reduce the CNS effect of levodopa.

References: 1. Bergquist et al. Neurology 2022;99:e965-e976.
2. Brod et al. Mov Disord. 2012;27(6):750-753
3. Trenkwalder et al. Neurology. 2019;92(13):e1487-e1496.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-function-in-parkinsons-disease-during-16h-treatment-with-intravenously-diz101-subcutaneously-diz102-or-intestinally-lcig-infused-levodopa/