To evaluate the effect of istradefylline (IST), an adenosine A_2A receptor antagonist, on levodopa dose escalation in patients with Parkinson’s disease (PD) and wearing-off phenomena.

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.

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.

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.