Pharmacokinetics and efficacy of a novel formulation of carbidopa-levodopa (Accordion Pill®) in Parkinson's disease.

Abstract

INTRODUCTION:

Dopamine replacement via levodopa (LD) remains the most effective treatment for Parkinson's disease (PD), yet its use is often associated with motor complications within several years of continued use. The Accordion Pill® (AP-CD/LD) is a novel drug delivery system based on gastric retention of multilayer films containing immediate-release (IR) carbidopa (CD) and immediate- and controlled-release LD. The AP-CD/LD was designed to improve the consistency of LD in the bloodstream while offering patients with PD more consistent symptom management.

METHODS:

This phase 2, multicenter, open-label, two-way randomized crossover study included 4 cohorts of participants with PD, each receiving AP-CD/LD (50/250 mg, 50/375 mg or 50/500 mg) twice daily in one treatment period and an active comparator in the other treatment period. Pharmacokinetics (PK) and efficacy were evaluated for AP-CD/LD vs IR-CD/LD. Treatment-emergent adverse events (TEAEs) and patient- and investigator-reported measures were also evaluated.

RESULTS:

Compared with IR-CD/LD, treatment with either AP-CD/LD dose resulted in more stable LD plasma concentrations in both fluctuating and non-fluctuating PD patients, and significantly decreased Cmax (57.1% and 66.8% decreases among fluctuating and non-fluctuating patients, respectively). Both AP doses significantly improved standard measures of motor symptoms: (daily OFF time, total ON time, and good ON time), as well as patient- and investigator-assessed measures, versus IR-CD/LD. The safety and tolerability profile of AP-CD/LD was consistent with the known properties of IR-CD/LD.

CONCLUSIONS:

AP technology demonstrated effective controlled-release PK performance and reduced motor response fluctuations in advanced PD patients. A phase 3 randomized controlled trial is currently underway.

• Authors: Peter A LeWitt, Nir Giladi, Nadav Navon
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 65 Pg. 131-138 (08 2019) ISSN: 1873-5126 [Electronic] England
• PMID: 31176632 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Drug Combinations
• carbidopa, levodopa drug combination
• Levodopa
• Carbidopa

Topics

• Aged
• Antiparkinson Agents (administration & dosage, pharmacokinetics)
• Carbidopa (administration & dosage, pharmacokinetics)
• Cohort Studies
• Cross-Over Studies
• Drug Combinations
• Drug Compounding
• Drug Delivery Systems (methods)
• Female
• Humans
• Levodopa (administration & dosage, pharmacokinetics)
• Male
• Middle Aged
• Parkinson Disease (diagnosis, drug therapy)
• Pilot Projects
• Proof of Concept Study
• Treatment Outcome