Improved Motor Function Achieved With High- vs Low-Dose Inhaled Levodopa in PD

High doses of inhaled levodopa (CVT-301) in patients with Parkinson disease (PD) were associated with improved motor function and other clinical outcomes vs low-dose CVT-301, according to study findings published recently in Neurological Sciences.

As the most commonly used first-line therapy in PD, levodopa in an inhalable powder formulation has been shown to remove the gastrointestinal and intestinal absorption-related issues found with oral delivery. Notably, 39% to 48% of patients taking oral levodopa were affected by motor fluctuations within 2 years of treatment initiation.

“This rate gradually increased as the disease progressed, increasing to 82% by the sixth year. For most patients with advanced PD, the OFF state accounts for more than a third of the time spent awake during the day,” said the study authors. “A meta-analysis has explored the significance of CVT-301 in the treatment of PD—it confirms the value of CVT-301 in the treatment of motor fluctuations in patients with PD. However, this study did not explore different doses of CVT-301.”

In a novel randomized controlled trial that has since updated findings of the meta-analysis, high-dose CVT-301 was more recommended, but researchers noted that higher levels of evidence-based medicine would make this conclusion more credible. Therefore, they conducted a meta-analysis of data from Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov, from the earliest available date to February 12, 2022, to evaluate the efficacy of high- and low-dose CVT-301 in patients with PD.

For the meta-analysis, included research comprised randomized clinical trials that enrolled participants with PD who used CVT-301 or placebo as intervention. Primary outcomes assessed were the Unified PD Rating Scale part III (UPDRS-III) score, time to turn and hold on from OFF to ON after medication, Patient Global Impression of Change (PGIC), and average daily OFF time. Six multicenter, randomized controlled trials that accounted for 1166 patients were included.

Compared with placebo, CVT-301 exhibited a statistically significant effect on the treatment of patients with PD with OFF episodes of medication intervals.

Between the high- and low-dose CVT-301 patient subgroups, those given high doses were associated with a significantly greater decrease in UPDRS Part III score 30 minutes after administration than the low-dose group (weighted mean difference [WMD] = − 4.51; 95% CI, −7.34 to −1.68; P = .002), and more patients in the high-dose group achieved and maintained an ON state up to 60 minutes after receiving CVT-301 (risk ratio [RR], 1.17; 95% CI, 1.08-1.27; P < .001).

Improved PGIC scores were also observed among more patients in the high- vs low-dose group (RR, 1.13; 95% CI, 1.05-1.21; P = .001).

“CVT-301 can enable patients with motor fluctuations to quickly reach the ON state and improve motor function after medication… Clinically, different doses of CVT-301 can be personalized to relieve OFF episodes according to the severity of the patient’s disease,” concluded the researchers.

“However, further clinical and pharmacological studies are needed to demonstrate the effect of high-dose CVT-301, and future studies should focus on the safety of long-term use of high-dose CVT-301.”

Reference

Yan Z, Wang W, Tao X, et al. High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson disease for the treatment of OFF episodes: a meta-analysis of randomized controlled trials. Neurol Sci. Published online July 30, 2022. doi:10.1007/s10072-022-06298-z