Abstract
<h3>Objective:</h3> To evaluate the effect of istradefylline (IST), an adenosine A<sub>2A</sub> receptor antagonist, on levodopa dose escalation in patients with Parkinson’s disease (PD) and wearing-off phenomena. <h3>Background:</h3> Clinical data suggest that the lowest possible levodopa dose should be used to balance treatment benefits against the risk of motor complications. IST is approved in Japan and the US as an adjunct to levodopa/decarboxylase inhibitors in patients with PD and wearing-off phenomena/off episodes. Robust data on the impact of IST on levodopa dose titration are lacking. <h3>Design/Methods:</h3> In this multicenter, randomized, open-label, parallel-group controlled study, 114 patients with PD and wearing-off phenomena receiving 300–400 mg/day levodopa were randomly assigned (1:1) to the IST or control group. Levodopa dose escalation was based on the clinical impression of severity. The primary endpoint was the cumulative additional levodopa dose throughout the 37-week treatment period. Changes in symptom rating scales, motor activity using a wearable device, and safety outcomes were evaluated as secondary endpoints. <h3>Results:</h3> In total, 105 patients (IST, n = 52; control, n = 53) were included in the efficacy and safety analyses. The cumulative additional levodopa dose as area under the curve was 5-fold significantly lower in the IST group than in the control group. Changes in symptom rating scales from baseline were comparable between the groups. Device-evaluated motor activities significantly improved from baseline to week 36 only in the IST group. Incidences of adverse drug reactions (ADRs) were 28.8% in the IST group and 13.2% in the control group. No serious ADRs occurred in either group. <h3>Conclusions:</h3> IST treatment effectively prevented the need for levodopa dose escalation, resulting in a lower cumulative levodopa dose during the study. Data from the wearable device suggest that more objective improvement in motor function may be achieved with IST than with levodopa dose escalation. <b>Disclosure:</b> Dr. Hatano has nothing to disclose. Dr. Kano has nothing to disclose. Dr. Sengoku has nothing to disclose. Mr. Yanagisawa has nothing to disclose. Prof. Nagayama has nothing to disclose.
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