%0 Clinical Study
%T Continuous Levodopa Delivery with an Intraoral Micropump System: An Open-Label Pharmacokinetics and Clinical Study.
%A Olanow CW
%A McIntyre D
%A Matarazzo M
%A Leinonen M
%A McGarry A
%A Kamp C
%A Kennedy J
%A Torti M
%A Kruger R
%A Obeso JA
%A Stocchi F
%A Heller E
%A Kieburtz K
%J Mov Disord
%V 39
%N 6
%D 2024 Jun 2
%M 38698639
%F 9.698
%R 10.1002/mds.29824
%X <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.