A Randomized Controlled Trial of Subcutaneous Apomorphine for Parkinson Disease: A Repeat Dose and Pharmacokinetic Study.

ABSTRACT

OBJECTIVES: This study is the first controlled trial to evaluate the efficacy and safety of subcutaneous apomorphine in Japanese patients with advanced Parkinson disease. METHODS: A phase II, multicenter, randomized, double-blind, parallel-group trial was undertaken in 16 patients with advanced Parkinson disease with wearing-off phenomenon to compare subcutaneous apomorphine versus placebo. The maintenance dose of apomorphine (1-6 mg per dose), determined individually for each patient by titration, was additionally administered 3 times at 2-hour intervals in the multiple-dose phase in which pharmacokinetics was evaluated. RESULTS: The mean (SD) maintenance apomorphine dose was 3.4 (1.4) mg (range, 2-6 mg). The change in the Unified Parkinson's Disease Rating Scale motor score 20 minutes after maintenance dose administration was significantly greater in the apomorphine group than in the placebo group (least squares mean, -24.0 vs -4.1, P = 0.021). Apomorphine treatment resulted in an "on" state approximately 20 minutes after dose administration, lasting for approximately 60 minutes. Apomorphine was rapidly absorbed, with the maximum plasma concentration (Cmax) reached in 0.367 to 0.383 hour. It was quickly eliminated with a half-life of 0.520 to 0.793 hour, suggesting no accumulation during multiple-dose phase. The Cmax of apomorphine at effective dose was presumed to be approximately 20 ng/mL. Apomorphine was well tolerated. CONCLUSIONS: Subcutaneous apomorphine is expected to provide a new treatment option in Japan as a rescue therapy. Two-hour interval injections did not cause reduced responses, and effective blood concentration was presumed to be approximately 20 ng/mL similar, to the previous study conducted at North America.