Long-term safety and efficacy of adjunctive rasagiline in levodopa-treated Japanese patients with Parkinson\u2019s disease

Nobutaka Hattori,Ryosuke Takahashi,Hideki Mochizuki,Shinichi Takeda,Akira Nishimura,Atsushi Takeda,Masahiro Nagai,Ryou Nakaya

doi:10.1007/s00702-018-1962-5

Abstract

Rasagiline is a monoamine oxidase type-B inhibitor in development in Japan for Parkinson’s disease (PD). This open-label study evaluated the long-term safety and efficacy of rasagiline in Japanese patients with PD receiving levodopa. Patients were aged 30–79 years and had wearing-off or weakened effect. Patients received rasagiline 1 mg/day for 52 weeks. The primary objective was to evaluate safety. Secondary endpoints included MDS-UPDRS Part II and Part III total scores (ON-state) and change from baseline in mean daily OFF-time. An additional endpoint was the Parkinson’s Disease Questionnaire-39 (PDQ-39) Summary Index (SI) score. In total, 222 patients were enrolled; 52.3% had wearing-off phenomena. Treatment-emergent adverse events (TEAEs) were mostly mild or moderate and occurred in 83.3% of patients; 63.1% had drug-related TEAEs; and 21.2% had TEAEs resulting in discontinuation. Fall (16.7%), nasopharyngitis (14.0%), and dyskinesia (10.8%) were the most frequent TEAEs. Serious TEAEs were reported in 17.6% of patients, and led to discontinuation in 9.5%. At week 52 (last-observation-carried forward), the mean change from baseline in MDS-UPDRS Part III total score (ON-state) was − 7.6; the mean change from baseline in daily OFF-time was − 0.89 h in patients with wearing-off phenomena at the start of the run-in period. The mean change from baseline in PDQ-39 SI was − 0.64. No major safety issues were observed during this 52-week trial of rasagiline as an adjunct to levodopa in Japanese patients. Mean changes in MDS-UPDRS scores and daily OFF-time suggested that adjunctive rasagiline treatment with levodopa was efficacious, with efficacy maintained for at least 52 weeks.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disease, that is second only in prevalence to Alzheimer’s disease and affects more than 300 per 100,000 individuals worldwide, most of whom are older than 50 years (Giovannoni et al 2016; Pagano et al 2016; Pringsheim et al 2014)
We recently reported the results of two randomized, double-blind, placebo-controlled, 26-week studies of rasagiline therapy in Japanese patients with PD (Hattori et al 2017, 2018)
We evaluated the safety and efficacy of long-term use of rasagiline 1 mg/day in combination with levodopa for up to 52 weeks in Japanese patients with PD

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disease, that is second only in prevalence to Alzheimer’s disease and affects more than 300 per 100,000 individuals worldwide, most of whom are older than 50 years (Giovannoni et al 2016; Pagano et al 2016; Pringsheim et al 2014). In Japan, 100–150 per 100,000 people suffer from the condition (Giovannoni et al 2016), the prevalence of which is expected to increase, in parallel with the anticipated increase in the proportion of older people in the population. The etiology of PD is complex, the key pathological feature is an early loss of dopaminergic neurons and reduced levels of dopamine in the nigrostriatal system (Kalia and Lang 2015). This is believed to be the main underlying cause of the characteristic motor symptoms of the condition, namely resting tremor, muscle rigidity, bradykinesia, and postural instability. Drugs that do not act directly on the dopaminergic system (and which are less commonly used therapeutically) include anticholinergic drugs and amantadine (Schapira and Olanow 2008)

Methods

Results

Conclusion