Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease

Robert A. Hauser, Aaron L. Ellenbogen, Leo Verhagen Metman, Ann Hsu, Martin J. O'Connell, Nishit B. Modi, Hsuan Ming Yao, Sherron H. Kell, Suneel K. Gupta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended-release formulation of carbidopa-levodopa, with an immediate-release carbidopa-levodopa formulation in advanced Parkinson's disease. We performed an open-label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate-release carbidopa-levodopa followed by IPX066 or IPX066 followed by immediate-release carbidopa-levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple-dose administration). Following a single dose of IPX066 or immediate-release carbidopa-levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate-release carbidopa-levodopa (P <.0001). Multiple-dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa C max was approximately 30% compared with immediate-release carbidopa-levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate-release carbidopa-levodopa. Larger, longer-term, well-controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066.

Original languageEnglish (US)
Pages (from-to)2246-2252
Number of pages7
JournalMovement Disorders
Volume26
Issue number12
DOIs
StatePublished - Oct 2011

Keywords

  • Extended-release levodopa
  • IPX066
  • Motor effects
  • Motor fluctuations
  • Parkinson's disease
  • Pharmacokinetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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