Abstract：
BACKGROUND: Double-blind studies have demonstrated that motor complications in Parkinson\'s disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth.
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.
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.
摘要：
背景：双盲研究表明，持续服用左旋多巴可以减少帕金森病（PD）的运动并发症。DopaFuse系统是一种新颖的,口内微型泵连接到固定器，并使用推进剂将左旋多巴/卡比多巴（LD/CD）连续输送到口中。
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。
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。
