Objective: To assess the safety, tolerability, and pharmacokinetics (PK) of a novel continuous levodopa-carbidopa oral pump (LCOP) delivery system in patients with early PD.

Background: Levodopa remains the gold standard of symptomatic treatment of Parkinson’s disease (PD). However, with disease progression and chronic treatment, motor and non-motor fluctuations can occur. Continuous levodopa infusions can reduce the risk of developing motor complications and improve quality of life but to date remain invasive, associated with potentially serious side effects and discomfort related to the need for a free standing pump. The LCOP gel delivery system is being studied to provide continuous levodopa delivery in a relatively non-invasive manner.

Method: We report on our experience with the first two Parkinson’s disease patients worldwide who have been treated by this novel therapeutic modality as a part of the open label phase IIb clinical trial (ClinicalTrials.gov Identifier: NCT04778176). This LCOP system is comprised of an intraorally placed mini pump that continuously releases LD/CD using pre-filled, single-use containers inserted into a custom dental retainer. Safety, tolerability, PK, and clinical function (on/off home diaries and UPDRS) were assessed at fixed intervals.

Results: The patients were treated at the Centre Hospitalier in Luxembourg. They were 56 and 59 years old, one male and one female, mean disease duration of 7 years, Hoehn and Yahr stage 2.5, and mean daily off time of 150 minutes at baseline. Each signed an institutional review board-approved informed consent prior to study entry. Participants were treated with 50mg/13mg LD/CD per hour orally administered continuously for approximately 12 hours during the day. Therapy was begun in an inpatient setting and continued at home for 14 days. A reduction to 30 and 0 minutes of off time respectively was observed, and there were no clinically significant adverse reactions.  PK analyses will be performed at the end of the study.

Conclusion: This is the first report of the use of this novel LCOP delivery system Parkinson’s Disease Patients with early PD. The treatment was safe and well tolerated, and there was a marked reduction in off time. The study is ongoing and PK results to confirm that LCOP provides continuous plasma levodopa levels are awaited.

References: Warren Olanow, C., et al., Continuous versus intermittent oral administration of levodopa in Parkinson’s disease patients with motor fluctuations: A pharmacokinetics, safety, and efficacy study. Movement Disorders. 2019 Mar;34(3):425-4290(0).
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MDS Abstracts - https://www.mdsabstracts.org/abstract/case-reports-of-first-experiences-worldwide-with-novel-continuous-oral-levodopa-dental-pump-in-parkinsons-disease-patients/