Background:ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson’s disease (PD) experiencing motor fluctuations Objective:Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD. Methods:This was a 28-day open-label study (NCT02577523) in PD patients with ≥2.5 hours/day of OFF time despite optimized treatment. Patients were randomized to treatment with either a 24-hour infusion (levodopa/carbidopa dose of 720/90 mg) or a 14-hour ‘waking-day’ infusion (levodopa/carbidopa dose of 538/68 mg plus a morning oral dose of 150/15 mg). In-clinic assessments of OFF time (primary endpoint) and ON time with or without dyskinesia were determined by a blinded rater over 8 hours (normalized to 16 hours). Results:A total of 38 patients were randomized and 33 (87% ) completed the study. Compared to baseline, OFF time for the overall population was reduced by a least squares (LS) mean[95% CI] of 2.0[– 3.3, – 0.7] hours (p = 0.003). ON time with no/mild dyskinesia was increased from baseline by a LS mean of 3.3[2.0, 4.6] hours (p < 0.0001), and ON time with moderate/severe dyskinesia was reduced by a LS mean of 1.2[– 1.8, – 0.5] hours (p≤0.001). Reduction in OFF time was larger in the 24-hour group (– 2.8[– 4.6, – 0.9] hours; p = 0.004) than in the 14-hour group (– 1.3[– 3.1, 0.5] hours; p = 0.16). Complete resolution of OFF time was observed in 42% (n = 8) of patients in the 24-hour group. Infusion site reactions were the most common adverse event. Conclusion:This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.

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持续皮下注射左旋多巴治疗帕金森病：一项随机研究

背景：ND0612 是一种连续皮下左旋多巴/卡比多巴给药系统，正在开发用于患有运动波动的帕金森病 (PD) 患者目的：评估两种 ND0612 给药方案对 PD 患者的疗效和安全性。方法：这是一项为期 28 天的开放标签研究 (NCT02577523)，针对 PD 患者，尽管进行了优化治疗，但仍然有≥2.5 小时/天的关断时间。患者随机接受 24 小时输注（左旋多巴/卡比多巴剂量为 720/90 毫克）或 14 小时“清醒日”输注（左旋多巴/卡比多巴剂量为 538/68 毫克加上早晨口服剂量的150/15 毫克）。有或没有运动障碍的关闭时间（主要终点）和开启时间的临床评估由不知情的评分者在 8 小时内确定（标准化为 16 小时）。结果：共有 38 名患者被随机分组​​，其中 33 名 (87%) 完成了研究。与基线相比，总体人群的关闭时间减少了 2.0[– 3.3, – 0.7] 小时的最小二乘 (LS) 均值 [95% CI] (p = 0.003)。无/轻度运动障碍的开启时间比基线增加了 3.3[2.0, 4.6] 小时的 LS 平均值（p < 0.0001），并且中度/重度运动障碍的开启时间减少了 1.2[– 1.8, – 0.5] 小时 (p≤0.001)。24 小时组（– 2.8[– 4.6, – 0.9] 小时；p = 0.004）的关闭时间减少幅度大于 14 小时组（– 1.3[– 3.1, 0.5] 小时；p = 0.16） . 在 24 小时组中，42% (n = 8) 的患者观察到 OFF 时间完全消退。输注部位反应是最常见的不良事件。结论：