Objective: To perform a pharmacokinetic (PK) study of the Accordion Pill™ carbidopa/levodopa (AP-CD/LD) and to determine if multiple doses can provide continuous delivery of LD.

Background: Stable plasma concentrations of CD/LD are associated with a reduced risk of motor complications in patients with Parkinson’s disease (PD). AP-CD/LD is a novel drug delivery system based on gastric-retention of multilayer films containing both immediate-release (IR) and controlled-release LD that is designed to provide LD plasma levels with a long elimination half-life (approximately 7 hours). It is anticipated that repeat dosing with AP-CD/LD will attenuate the low plasma trough levels associated with intermittent doses of standard LD and will reduce plasma variability.

Methods: This study will compare the PK of AP-CD/LD 500 mg dosed TID with standard IR-CD/LD dosed 5 times per day. Eligible patients will present to clinic on day 1 in the practically-defined OFF state and be treated with standardized doses of IR levodopa every 3 hours. PK assessments will be performed every 30 min for 16h and again at 24h. Patients will then be discharged and instructed to take AP-CD/LD 50mg/500mg TID (every 5 hours). Patients will return to clinic on day 8 in the practically-defined OFF state and receive AP-CD/LD at 0, 5, and 10h. PK assessments will be performed as on day 1. The primary endpoint is the LD fluctuation index [Cmax – Cmin/Caverage]). Secondary endpoints include coefficient of variation [CV]) as well as standard PK assessments (Cmax, tmax, Cmin, AUC, and elimination half-life (t1/2). Sample size calculations indicate that 12 patients will provide >80% power to detect a difference in fluctuation index of 25%, assuming standard deviation equal to this difference with alpha = 0.05.

Results: We anticipate 2 study centers in Italy will begin enrolling 12 patients in April 2018.

Conclusions: This crossover PK study will compare thrice-daily dosing of AP with 5x-daily dosing of standard CD/LD. The study will determine if AP TID can provide stable plasma levels of LD that attenuate or eliminate the low trough levels associated with standard LD administration.

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