title: Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease.
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.
authors.affiliation: Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Ellenbogen
authors.forename: Leo Verhagen
authors.initials: LV
authors.lastname: Metman
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Nishit B
authors.initials: NB
authors.lastname: Modi
authors.forename: Hsuan-Ming
authors.initials: HM
authors.lastname: Yao
authors.forename: Sherron H
authors.initials: SH
authors.lastname: Kell
authors.forename: Suneel K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000097:blood / Q000627:therapeutic use*; D002230:Carbidopa / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa