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

Author:

Olanow C. Warren12ORCID,McIntyre Deborah3,Matarazzo Michele4ORCID,Leinonen Mika2,McGarry Andrew25,Kamp Cornelia26,Kennedy Julie2,Torti Margherita2,Kruger Rejko3,Obeso José A.7,Stocchi Fabrizio8ORCID,Heller Ephraim9,Kieburtz Karl26

Affiliation:

1. Department of Neurology Mount Sinai School of Medicine New York New York USA

2. Clintrex Research Corporation Sarasota Florida USA

3. Luxembourg Institute of Health, Transversal Translational Medicine Strassen Luxembourg

4. Centro Integral de Neurociencias AC (CINAC), Hospital Universitario HM Puerta del Sur, Fundación de Investigación HM Hospitales Madrid Spain

5. Cooper Medical School of Rowan University Camden New Jersey USA

6. Center for Health & Technology, University of Rochester Rochester New York USA

7. CEU San Pablo University Madrid; Network Center for Biomedical Research in Neurodegenerative Diseases Madrid Spain

8. University San Raffaele Roma and Institute for Research and Medical Care IRCCS San Raffaele Rome Italy

9. SynAgile Corporation San Jose California USA

Abstract

AbstractBackgroundDouble‐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.ObjectivesEvaluate 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.MethodsThis 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.ResultsContinuous 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.ConclusionsContinuous 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.

Publisher

Wiley

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