Abstract
Objectives Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). Methods ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Results and Conclusions Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 47-55 |
| Number of pages | 9 |
| Journal | Clinical neuropharmacology |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2018 |
Funding
P.A.L. and L.V.M. have served as consultants and have been investigators in clinical trials sponsored by Impax Laboratories, Inc. P.A.L. has also served as a consultant or advisor for Britannia, Acorda, Concit, Dexcel, Depomed, Insightec, Intec, Ipsen, Merck, Merz, NeuroDerm, Noven, Parkinson Study Group, Pfizer, ProStrakan, Teva, and US WorldMeds and has received speaker honoraria from the International Parkinson's Disease and Movement Disorders Society, Lundbeck, US WorldMeds, and the World Parkinson Congress. He is compensated for services as editor-in-chief of Clinical Neuropharmacology and serves without compensation on the editorial boards of Journal of Neural Transmission, Translational Neurodegeneration, and Journal of Parkinson's Disease. The Parkinson's Disease and Movement Disorders Program that P.A.L. directs has received clinical research grant support (for conducting clinical trial and other research) from Acorda, Adamas, Biotie, Great Lakes Neurotechnologies, Kyowa, The Michael J. Fox Foundation for Parkinson's Research, Pharma 2B, and US WorldMeds. L.V.M. received compensation from Medtronic, St Jude Medical, Britannia, US WorldMeds, and Cynapsus for consulting services. He has also received financial support for research activities from Medtronic, Boston Scientific, Adamas, Osmotica, Pfizer, US WorldMeds, National Institutes of Health, and Michael J Fox Foundation, in a role as principal investigator for research studies. R.R., S. Khanna, S. Kell, and S.G. are employees of Impax Laboratories, Inc, and hold Impax stock and/or stock options. Address correspondence and reprint requests to Peter A. LeWitt, MD, Henry Ford Hospital, 6777 W Maple Rd, West Bloomfield, MI 48322; E‐mail: [email protected] These studies were funded by Impax Laboratories, Inc. Medical writing support was provided by Gerard D'Angelo, PhD, and Robin Smith, PhD, of The Curry Rockefeller Group, LLC, supported by Impax Laboratories, Inc.
Keywords
- Amantadine
- Dopaminergic agonist
- Extended release
- Levodopa
- Monoamine oxidase inhibitor
ASJC Scopus subject areas
- Clinical Neurology
- Pharmacology (medical)
- Pharmacology
