Clinical benefits and optimal dosage of istradefilline in Parkinson's disease

Objective: An open‐labelled, randomized study was conducted to clarify optimal dosage of istradefilline obtaining clinical benefits in Parkinson's disease. Background: Istradefilline has been approved and used in Japan as 20 mg/day against wearing‐off and 40 mg/day against more severe motor symptoms. However, therapeutic optimal dosage of istradefilline is unclear to manage advanced patients with Parkinson's disease. Methods: Patients with Parkinson's disease were randomly divided into two groups by dosage of 20 mg/day and 40 mg/day of istradefilline, who showed off time more than 2 hours during awaking time confirmed with a self‐assessment symptom diary. Off time and motor severity using with MDS‐UPDRS were evaluated at visits of baseline, 4 weeks and 8weeks, and statistically analyzed. Nonmotor symptom scale (NMSS), Parkinson's disease queationnaire‐39 (PDQ‐39) and patient's global impression of improvement (PGI‐I) were also evaluated as secondary measures. This study was approved by the ethical committee of our institute and performed with the written informed consent. Results: In all patients, istradefilline could improve off time (p50.01) and motor severity (p50.05). In 20 mg/day group, off time and motor severity showed certain tendencies of improvement without significant changes. In 40 mg/day group, these showed significant improvement (p50.04 and 0.05). In secondary measures, MDS‐UPDRS part I and NMSS were significantly improved (p50.05 and 0.05), whereas PDQ‐39 was unchanged. In PGI‐I, 33% of patients manifested more than moderate improvement of their daily difficulties. Conclusions: This study shows that istradefilline has clinical benefits in off time and motor severity, as consistent with prior clinical trials. In addition, this study suggested that 40 mg/day of istradefilline is recommended when 20 mg/day was ineffective in clinical practice. Furthermore, istradefilline may have some benefits in the nonmotor aspects, which are clinically heterogenous and resulted in a difficulty to improve qualities of patients' lives. In order to verify the results of this study, some limitations should be solved because this study was small and open‐labelled.