Adjunct rasagiline to treat Parkinson\u2019s disease with motor fluctuations: a randomized, double-blind study in China

Zhenxin Zhang,Baorong Zhang,Xiaoying Zhang,Jian Wang,Gang Zhao,Yansheng Li,Shenggang Sun,Rong Peng,Jimei Li,Xiangru Sun,Yanping Wang,Haibo Chen,Ming Shao,Qiumin Qu,Shengdi Chen,Chunfeng Liu,Suiqiang Zhu,Xiaoping Pan

doi:10.1186/s40035-018-0119-7

Abstract

BackgroundThe use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies. This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease, as a product registration study.MethodsThis 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations. The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks. Secondary endpoints were Clinical Global Impressions – Improvement (CGI-I), and change in Unified Parkinson’s Disease Rating Scale (UPDRS) Activities of daily living (ADL) and Motor scores. Patient well-being (EQ-5D), and the frequency of adverse events were also assessed.ResultsIn total, 324 levodopa-treated patients were randomized to rasagiline 1 mg/day (n = 165) or placebo (n = 159). Over 16 weeks, rasagiline statistically significantly reduced the mean [95% confidence interval] total daily OFF time versus placebo (− 0.5 h [− 0.92, − 0.07]; p = 0.023). There were also statistically significant improvements versus placebo in CGI-I (− 0.4 points [− 0.61, − 0.22]; p < 0.001), UPDRS-ADL OFF (− 1.0 points [− 1.75, − 0.27]; p = 0.008), and UPDRS-Motor ON (− 1.6 points [− 3.05, − 0.14]; p = 0.032) scores, as well as the EQ-5D utility index (p < 0.05). Rasagiline was safe and well tolerated.ConclusionsIn levodopa-treated Chinese patients with Parkinson’s disease and motor fluctuations, adjunct rasagiline 1 mg/day statistically significantly reduced OFF time, and improved daily function and overall well-being, versus placebo. Consistent with findings in other countries, adjunct rasagiline was proven efficacious and well tolerated in Chinese patients.Trial registration numberNCT01479530. Registered 22 November 2011.

Highlights

The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies
Building on the findings of two large-scale registration studies (LARGO and PRESTO) set in Europe/America [16, 17], the current study investigated the efficacy and safety of rasagiline 1 mg/day as adjunct to levodopa in a Chinese population of patients with Parkinson’s disease (PD) and motor fluctuations
The effect of rasagiline in reducing daily OFF time (− 1.25 h) was comparable to that seen in Caucasian patients in the LARGO study (− 1.18 h), the placebo response in the current study was greater than in LARGO (− 0.76 h compared with − 0.40 h) [16]

Summary

Introduction

The use of adjunct rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations is supported by findings from large-scale clinical studies. PD prevalence in China is estimated at 1.7% in individuals aged 65 or older– a rate comparable to that seen in European and other Asian countries [1, 2]. A multicenter survey in China found the overall prevalence rate for wearing-off in Chinese PD patients to be 46.5%, which is in line with reports from other countries [11]. Studies show that motor complications can appear relatively early, within a year of initiating levodopa [5, 12,13,14], and that the effectiveness of levodopa decreases with disease progression [6]

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