Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study. (August 2018)

• Record Type: Journal Article
• Authors: Hattori, Nobutaka; Takeda, Atsushi; Takeda, Shinichi; Nishimura, Akira; Kato, Masafumi; Mochizuki, Hideki; Nagai, Masahiro; Takahashi, Ryosuke
• Is Part Of: Parkinsonism & related disorders. Volume 53(2018)
• Page Start: 21
• Page End: 27
• Publication Date: 2018-08
• Subjects: Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2018.04.025
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. Methods: Patients aged 30–79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. Results: In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were −0.84 h (rasagiline 1 mg/day) and −0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: −1.27, −1.74, and −2.51 (0.5 mg/day) and −1.27, −2.14, and −3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). Conclusions: As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised. Highlights: Study of adjunctive rasagiline in Japanese PD patients with wearing-off phenomena. Patients received either 0.5 mg/day or 1 mg/day rasagiline or placebo for 26 weeks. Rasagiline provided significant improvements in mean daily OFF-time versus placebo. Rasagiline showed significant improvements in MDS-UPRDS Part II & III total scores. No important safety concerns were raised.