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. OBJECTIVES: 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.
ABSTRACT
BACKGROUND: Laboratory and clinical evidence indicate that continous delivery of levodopa is associated with reduced motor complications compared to standard intermittent levodopa. OBJECTIVE: To assess the pharmacokinetics and efficacy of continuous oral delivery of l-dopa/carbidopa in PD patients with motor fluctuations. METHODS: Eighteen PD patients with motor fluctuations were enrolled in an open-label study comparing pharmacokinetics and efficacy measures between standard intermittent oral l-dopa/carbidopa and "continuous" oral l-dopa/carbidopa. Continuous treatment was operationally defined as sips of an l-dopa dispersion at 5- to 10-minute intervals. On day 1, patients received their usual oral l-dopa/carbidopa doses. On day 2, patients received l-dopa/carbidopa dose by "continuous" oral administration. On day 3, patients received a single dose of oral l-dopa/carbidopa followed by continuous administration of l-dopa/carbidopa. Each study period was 8 hours, and the total l-dopa/carbidopa dose administered was the same on each day. Analyses of variability were primarily-based samples drawn between 4 and 8 hours when subjects were in a relative steady state. RESULTS: There was less variability in plasma l-dopa concentration with continuous versus intermittent oral l-dopa/carbidopa treatment (fluctuation index was 0.99 ± 0.09 vs. 1.38 ± 0.12 [P < 0.001] and coefficient of variation was 0.35 ± 0.03 vs. 0.49 ± 0.04 [P < 0.001]). Mean OFF time was decreased by 43% (P < 0.001) with continuous oral l-dopa therapy. No safety or tolerability issues were observed. CONCLUSIONS: Continuous oral delivery of l-dopa/carbidopa was associated with less plasma variability and reduced off time in comparison to standard intermittent oral l-dopa/carbidopa therapy. © 2019 International Parkinson and Movement Disorder Society.
