Objective: To perform a pharmacokinetic (PK) assessment of a novel carbidopa/levodopa drug delivery system (Accordion Pill™; AP-CD/LD) and to determine if multiple doses of AP-CD/LD can provide relatively continuous delivery of LD compared with immediate-release (IR)-CD/LD in participants with Parkinson’s disease (PD).

Background: Stable plasma concentrations of CD/LD are associated with a reduced risk of motor complications in patients with Parkinson’s Disease (PD). The AP-CD/LD drug delivery system is based on gastric retention of multilayer films containing both IR and controlled-release LD to provide LD plasma levels with a long elimination half-life (approximately 7 hours).

Method: This open-label crossover study compared the PK of AP-CD/LD 500mg dosed thrice daily TID with 1.5 tablets of standard IR-CD/LD 25mg/100mg dosed 5x daily. Eligible participants presented to the clinic on day 1 in the practically-defined OFF state and were treated with standard IR levodopa at 3-h intervals. PK assessments were performed every 30 min for 16 h and again at 24 h. Participants were discharged and instructed to take AP-CD/LD 50mg/500mg TID at 5-h intervals. Participants returned to the clinic on day 8 in the practically-defined OFF state and received AP-CD/LD at 0, 5, and 10 h. PK assessments were performed as described on day 1. The primary endpoint was the LD fluctuation index ([Cmax – Cmin]/Caverage) at steady state (4 to 16 h). Secondary endpoints included coefficient of variation (CV) at steady state as well as standard PK (Cmax, tmax, Cmin, AUC), and elimination half-life (t1/2), and safety and tolerability.

Results: 12 PD patients participated in the study. Treatment with AP-CD/LD 50mg/500mg TID resulted in significantly less variability in LD plasma concentration versus standard IR-CD/LD therapy with a mean difference in fluctuation index (95% confidence interval) of 0.63 (0.24 – 1.03; P=0.005). Similar results were observed for all sensitivity analyses and for the key secondary endpoint of the LD coefficient of variation (P=0.047). No adverse events were reported with AP-CD/LD 50mg/500mg treatment.

Conclusion: As reduced variability in plasma LD concentration has been associated with reduced motor complications, these preliminary results suggest that treatment with AP-CD/LD may reduce motor complications compared with standard IR-CD/LD treatment in advanced PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetics-of-accordion-pill-carbidopa-levodopa-following-multiple-doses-in-patients-with-parkinsons-disease/