Session Information
Date: Saturday, October 6, 2018
Session Title: Parkinson’s Disease: Clinical Trials, Pharmacology And Treatment
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
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.
To cite this abstract in AMA style:
C. Olanow, K. Kieburtz, J. Dubow, F. Stocchi, J. Meckler, N. Navon, R. Gendreau. Design of a Pharmacokinetics Study with Multiple Doses of Accordion Pill™ Carbidopa/Levodopa in Patients with Parkinson’s disease [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/design-of-a-pharmacokinetics-study-with-multiple-doses-of-accordion-pill-carbidopa-levodopa-in-patients-with-parkinsons-disease/. Accessed October 10, 2024.« Back to 2018 International Congress
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/