Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules. Issue 1 (January 2019)

• Record Type: Journal Article
• Authors: Modi, Nishit B.; Mittur, Aravind; Rubens, Robert; Khanna, Sarita; Gupta, Suneel
• Is Part Of: Clinical neuropharmacology. Volume 42:Issue 1(2019)
• Publication Date: 2019-01
• Subjects: IPX203 -- levodopa -- Parkinson disease -- pharmacodynamics; Neuropharmacology -- Periodicals; 615.78
• DOI: 10.1097/WNF.0000000000000314
• Languages: English
• ISSNs: 0362-5664

Abstract

Abstract : Objective: IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-release (IR) CD-LD and extended-release CD-LD (Rytary). Methods: This was a randomized, open-label, rater-blinded, multicenter, single-dose crossover study. Blinded clinicians assessed subject's motor state and Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores for up to 10 hours postdose. Duration of effect was determined using improvement thresholds in the MDS-UPDRS part III. Results: Levodopa concentrations increased rapidly and similarly across all 3 treatments and were sustained for a longer duration after IPX203 dosing. All treatments exhibited a rapid onset of pharmacodynamic effect, whereas IPX203 had a significantly longer duration of effect based on MDS-UPDRS part III scores compared with IR CD-LD ( P < 0.0001) and Rytary ( P ⩽ 0.0290). IPX203 had a 2.7-hour advantage over IR CD-LD ( P < 0.0001) and a 0.9-hour advantage over Rytary in "off" time ( P = 0.023) and in "good on" time (2.6 hours more than IR CD-LD, P < 0.0001; 0.9 hours more than Rytary, P = 0.0259) as measured by the Investigator Assessment of Subject's Motor State. Subjects were 77% more likely to require rescue following IR CD-LD treatment compared with IPX203 (hazard ratio, 0.23; P < 0.0001). More subjects reported treatment-emergent adverse effects during IR CD-LD (28.0%) and IPX203 (19.2%) than during Rytary (8.0%) treatment. Conclusions: Compared with Rytary and IR CD-LD, IPX203 had a longer pharmacodynamic effect consistent with LD pharmacokinetics for the 3 treatments. The safety and tolerability of IPX203 were similar to those of IR CD-LD and Rytary.