OBJECTIVE: Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations.
METHODS: This was a 2-week, open-label study (NCT04778176) in 16 PD patients treated with ≥4 levodopa doses/day and experiencing motor fluctuations. On Day 1 (clinic setting) patients received their usual dose of standard LD/CD; DopaFuse therapy was initiated on Day 2, and on Day 3 patients received DopaFuse plus a morning oral LD/CD dose. Patients returned home on Days 4-14 and returned for in-clinic assessment on Day 15.
RESULTS: Continuous DopaFuse delivery of LD/CD was associated with reduced variability in plasma levodopa levels compared to oral LD/CD (mean ± SD levodopa Fluctuation Index reduced from 2.15 ± 0.59 on Day1 to 1.50 ± 0.55 on Day 2 (P = 0.0129) and to 1.03 ± 0.53 on Day 3 (P < 0.0001)). This pharmacokinetic improvement translated into significantly reduced OFF time with DopaFuse therapy (reduction of -1.72 ± 0.37 h at Day 15; P = 0.0004) and increased ON time without severe dyskinesias (increase of 1.72 ± 0.37 h at Day 15; P = 0.0004) versus oral LD/CD administration. DopaFuse therapy was not associated with any clinically significant adverse events.
CONCLUSIONS: Continuous delivery of LD/CD using the DopaFuse system was associated with significantly less variability in plasma levodopa concentrations and reductions in OFF time compared to treatment with standard oral LD/CD therapy and was well tolerated. © 2024 International Parkinson and Movement Disorder Society.
目的:评估安全性,药代动力学,在有运动波动的PD患者中,通过DopaFuse系统递送的LD/CD与间歇剂量标准口服LD/CD治疗相比的疗效。
方法:这是一个2周,开放标签研究(NCT04778176)纳入16例接受≥4次左旋多巴剂量/日治疗并经历运动波动的PD患者.在第1天(临床设置),患者接受其通常剂量的标准LD/CD;在第2天开始DopaFuse治疗,并且在第3天,患者接受DopaFuse加早晨口服LD/CD剂量。患者在第4-14天返回家中并在第15天返回进行临床评估。
结果:与口服LD/CD相比,连续DopaFuse递送LD/CD与血浆左旋多巴水平变异性降低相关(平均±SD左旋多巴波动指数从第1天的2.15±0.59降低至第2天的1.50±0.55(P=0.0129)和第3天的1.03±0.53(P<0.0001)))。与口服LD/CD相比,这种药代动力学改善转化为DopaFuse治疗的OFF时间显着减少(第15天减少-1.72±0.37h;P=0.0004),而没有严重运动障碍的ON时间增加(第15天增加1.72±0.37h;P=0.0004)。DopaFuse治疗与任何临床上显著的不良事件无关。
结论:与标准口服LD/CD治疗相比,使用DopaFuse系统连续递送LD/CD与血浆左旋多巴浓度的变异性和OFF时间的减少相关,并且耐受性良好。©2024国际帕金森和运动障碍协会。