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Efficacy and Safety of Extended- Versus Immediate-Release Pramipexole in Japanese Patients With Advanced and L-dopa–Undertreated Parkinson Disease: A Double-Blind, Randomized Trial

Mizuno, Yoshikuni MD*; Yamamoto, Mitsutoshi MD; Kuno, Sadako MD, PhD; Hasegawa, Kazuko MD§; Hattori, Nobutaka MD; Kagimura, Tatsuro MPH; Sarashina, Akiko MSc; Rascol, Olivier MD, PhD#; Schapira, Anthony H.V. MD, DSc, FRCP, FMedSci**; Barone, Paolo MD, PhD††; Hauser, Robert A. MD, MBA‡‡; Poewe, Werner MD§§ and The Pramipexole ER Study Group

doi: 10.1097/WNF.0b013e31825f77b9
Original Articles
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Objectives To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa–treated patients with Parkinson disease (PD).

Methods After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa–related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase.

Results Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson’s Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER.

Conclusions In L-dopa–treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

*Department of Neuroregenerative Medicine, Kitasato University School of Medicine, Kanagawa; †Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu; ‡Center of Parkinson Disease and Neuro-Intractable Diseases, Kyoto Sijyo Hospital, Kyoto; §Department of Neurology, National Hospital Organization, Sagamihara National Hospital, Sagamihara; ∥Department of Neurology, Juntendo University School of Medicine; ¶Nippon Boehringer Ingelheim Co., Ltd, Tokyo, Japan; #Clinical Investigation Center, INSERM CIC-9203 and UMR-825 and Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, Toulouse, France; **Institute of Neurology, University College London, London, UK; ††University of Salerno and IDC Hermitage-Capodimonte, Naples, Italy; ‡‡Department of Neurology, University of South Florida College of Medicine, Tampa, FL; and §§Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

This study was supported by Boehringer Ingelheim.

Conflicts of Interest and Source of Funding: Dr Yoshikuni Mizuno has received financial support from Boehringer Ingelheim for this study and has received compensation for consulting services from Boehringer Ingelheim, FP Pharmaceutical, Kyowa, Novartis, and Otsuka. Also, the department he is the chairman of has been donated by Boehringer Ingelheim and Medtronics. Dr Mitsutoshi Yamamoto has received financial support from Boehringer Ingelheim for this study and has received compensation for consulting services from Boehringer Ingelheim, GlaxoSmithKline, and Novartis. Dr Sadako Kuno has received financial support from Boehringer Ingelheim for this study and has received compensation for consulting services from Boehringer Ingelheim, Dainippon Sumitomo Pharma, FP Pharmaceutical Corporation, GlaxoSmithKline, Kyowa Hakko Kirin Company, Novartis, Otsuka Pharmaceutical Company, and Solvay. Dr Kazuko Hasegawa has received compensation for consulting services from Dainippon Sumitomo Pharma. Dr Nobutaka Hattori has received financial support from Boehringer Ingelheim for this study and has received compensation for consulting services from Boehringer Ingelheim, FP Pharmaceutical Corporation, GlaxoSmithKline, Kyowa Hakko Kirin Company, Novartis, Otsuka Pharmaceutical Company, and Schering-Plough. Mr Tatsuro Kagimura is an employee of Nippon Boehringer Ingelheim Co., Ltd. Ms. Akiko Sarashina is an employee of Nippon Boehringer Ingelheim Co., Ltd. Dr Olivier Rascol has received financial support from Boehringer Ingelheim for this study and has received grants or consulting fees from Boehringer Ingelheim, Eisai, GlaxoSmithKline, Lundbeck, Novartis, Schering, Solvay, Teva Neuroscience, and UCB. Dr Anthony Schapira has received financial support from Boehringer Ingelheim for this study and has received honoraria or consulting fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, Orion, Teva-Lundbeck, and UCB. Dr Paolo Barone has received financial support from Boehringer Ingelheim for this study and has received compensation for consulting services and research support from Boehringer Ingelheim, Lundbeck, Merck Serono, Novartis, and Schwarz Pharma/UCB. Dr Robert Hauser has received financial support from Boehringer Ingelheim for this study and has received honoraria, consulting fees, or grants from Allergan Neuroscience, Biogen Idec, Boehringer Ingelheim, Chelsea, Genzyme, GlaxoSmithKline, Impax, Ipsen (formerly Vernalis), Lundbeck, Merck Serono/EMD Serono, Schwartz, Shire, Novartis, Quintiles, Santhera, Schering-Plough, Solvay, Teva Neuroscience, and Xenoport. Dr Werner Poewe has received financial support from Boehringer Ingelheim for this study and has received honoraria or consulting fees from Boehringer Ingelheim, GlaxoSmithKline, Lundbeck, Merck Serono, Novartis, Orion, Solvay, Teva, and UCB.

Address correspondence and reprint requests to Yoshikuni Mizuno, MD, Department of Neuroregenerative Medicine, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara, Kanagawa 252-0380, Japan; E-mail: y_mizuno@juntendo.ac.jp

© 2012 Lippincott Williams & Wilkins, Inc.