Assess the safety, PK, and efficacy of levodopa/carbidopa (LD/CD) delivered continuously by an intra-oral micropump (DopaFuse) compared with standard oral LD/CD.

It is well-established that continuous delivery of levodopa/carbidopa (LD/CD) is associated with significant improvement in ON time without troublesome dyskinesia and OFF time in advanced PD patients. The DopaFuse system attaches to a retainer and uses a propellant to deliver LD/CD continuously into the mouth, thereby avoiding the need for surgical procedures, cumbersome pumps, and the development of infusion site reactions. 

16 patients participated in a 2-week, open-label trial. Patients were treated in clinic as follows: Day-1, usual dose of standard LD/CD; Day-2, continuous delivery of LD/CD with DopaFuse; Day-3, continuous delivery of LD/CD with DopaFuse after a single morning dose of standard LD/CD. Patients were sent home on Days 4-14 and treated with the same regimen as Day-3, and returned to clinic on Day-15. Levodopa PK was measured at 30-60min intervals for 12h on Days 1, 2, and 3. Motor state was evaluated at 30-min intervals for 12h on Days 1, 3, and 15.

In comparison to standard LD/CD treatment (day1), continuous intra-oral delivery was associated with significantly less variability in plasma levodopa as determined by fluctuation index (P=0.01 and P<0.001 on Day- 2 and Day-3 respectively) and Coefficient of Variation (P=0.02 and P<0.001 on Day-2 and Day-3 respectively). ON time without severe dyskinesia and OFF time on Day-3 and -15 each significantly improved with DopaFuse (P<0.001) as was UPDRS-part II at Day-15 (P=0.016). There were no dropouts and no clinically significant adverse events. 

Continuous delivery of LD/CD using the DopaFuse System was well tolerated. DopaFuse was associated with significantly less variability in plasma levodopa and significant improvement in measures of motor function and ADLs in comparison to treatment with standard intermittent LD/CD.