Continuous Levodopa Delivery with an Intraoral Micropump System: An Open-Label Pharmacokinetics and Clinical Study

C. Warren Olanow*, Deborah McIntyre, Michele Matarazzo, Mika Leinonen, Andrew McGarry, Cornelia Kamp, Julie Kennedy, Margherita Torti, Rejko Kruger, José A. Obeso, Fabrizio Stocchi, Ephraim Heller, Karl Kieburtz

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)945-954
JournalMovement Disorders
Volume39
Issue number6
Early online date2 May 2024
DOIs
Publication statusPublished - Jun 2024

Keywords

  • continuous delivery
  • DopaFuse
  • intraoral
  • micropump
  • motor fluctuations
  • Parkinson's disease
  • retainer

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