Onset and duration of effect of extended-release carbidopa-levodopa in advanced Parkinson’s disease
Received 5 October 2017
Accepted for publication 17 January 2018
Published 22 March 2018 Volume 2018:14 Pages 839—845
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Prof. Dr. Roumen Kirov
Peer reviewer comments 2
Editor who approved publication: Dr Roger Pinder
Robert A Hauser,1 Aaron Ellenbogen,2 Sarita Khanna,3 Suneel Gupta,3 Nishit B Modi3
1Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Tampa, FL, USA; 2Quest Research Institute, Bingham Farms, MI, USA; 3Impax Laboratories, Inc., Hayward, CA, USA
Background: In patients with Parkinson’s disease (PD), oral dosing of extended-release carbidopa-levodopa (Rytary, IPX066 [ER CD-LD]) achieves peak levodopa plasma concentrations within 1 hour and maintains them for 4–6 hours.
Aims: To compare the onset and duration of ER CD-LD benefit with those of immediate-release carbidopa-levodopa (IR CD-LD) in PD patients with motor fluctuations, using crossover data, and to evaluate which threshold values of improvement in finger-tapping and Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores yield results most similar to those for trained raters’ “on”/“off” assessments.
Methods: Patients underwent serial “on”/“off” rating and provided serial finger-tapping and UPDRS motor scores after receiving, in an “off” state, their usual morning IR dose or an ER dose designed to produce a similar levodopa peak concentration. Predefined improvement thresholds for analysis were 10%, 15%, and 20% increases in finger-tapping score and 2.5, 5, 7, and 11-point decreases in UPDRS motor score. Serial plasma samples were assayed for levodopa.
Results: Among 27 patients, mean time to onset of an “on” state was similar for ER compared with IR CD-LD (0.83 vs 0.81 hour), but mean duration was significantly longer for ER CD-LD than for IR CD-LD (5.56 vs 2.69 hours; P<0.0001). Duration was best matched by a ≥20% improvement in finger-tapping, a ≥11-point improvement in UPDRS motor score, and a levodopa plasma concentration ≥1,000 ng/mL.
Conclusion: For ER CD-LD, observer assessments of “on” state were corroborated by sustained treatment effects. Correlations among “on”-state duration, finger-tapping score, and UPDRS motor score may suggest clinically relevant thresholds for acute assessment of treatment benefit.
Keywords: Rytary, carbidopa-levodopa, Parkinson’s disease, treatment, duration of effect, motor fluctuations
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