Improvement in motor function achieved with high or low dose inhaled levodopa in PD


Significantly more patients with Parkinson’s disease (PD) achieved improved motor function and clinical outcomes when treated with high or low dose inhaled levodopa.

According to the results of a study recently published in Neurological sciences.

As the most commonly used first-line treatment in PD, levodopa in an inhalable powder formulation has been shown to eliminate the problems with gastrointestinal and intestinal absorption seen with oral administration. Notably, 39% to 48% of patients taking oral levodopa were affected by motor fluctuations within 2 years of starting treatment.

“This rate gradually increased as the disease progressed, rising 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,” the study authors said. “A meta-analysis explored the importance 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 new randomized controlled trial that has since updated meta-analysis results, high-dose CVT-301 was more recommended, but the researchers noted that higher levels of evidence-based medicine would make this conclusion more believable. Therefore, they conducted a meta-analysis of data from Medline, EMBASE, Cochrane Library, and, from the earliest available date to February 12, 2022, to assess the efficacy of high- and low-dose CVT-301 in patients. with DP.

For the meta-analysis, included research included randomized clinical trials that recruited participants with PD who used CVT-301 or placebo as an intervention. Primary outcomes assessed were Unified PD Rating Scale part III (UPDRS-III) score, time to switch from OFF to ON after treatment, patient global impression of change (PGIC), and daily OFF time medium. Six multicenter randomized controlled trials totaling 1166 patients were included.

Compared to placebo, CVT-301 showed a statistically significant effect in treating PD patients with medication interval OFF episodes.

Between the high-dose and low-dose CVT-301 patient subgroups, those who received high doses were associated with a significantly greater decrease in UPDRS Part III score at 30 minutes after dosing than the low-dose group ( weighted mean difference[WMD]= – 4.51; 95% CI, -7.34 to -1.68; P= 0.002), and more patients in the high dose group achieved and maintained an ON state up to 60 minutes after receiving CVT-301 (relative risk [RR], 1.17; 95% CI, 1.08-1.27; P

Improved PGIC scores were also seen in more patients in the high or low dose group (RR, 1.13; 95% CI, 1.05-1.21; P= 0.001).

“CVT-301 can enable patients with motor fluctuations to quickly achieve ON state and improve motor function after taking medication…Clinically, different doses of CVT-301 can be customized to relieve the OFF episodes as a function of patient disease severity,” the researchers concluded.

“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. “


Yan Z, Wang W, Tao X, et al. High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson’s 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


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