Motor Fluctuations

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Research Article

Apomorphine Subcutaneous Injection for the Management of Morning Akinesia in Parkinson’s Disease

By Stuart Isaacson MD,*, Mark Lew MD, William Ondo MD, Jean Hubble MD, Thomas Clinch BS and Fernando Pagan MD

ABSTRACT Background In patients with motor fluctuations complicating Parkinson’s disease (PD), delays in time-to-ON with levodopa are common. This open-label study aimed to assess the effect of apomorphine on time-to-ON in PD patients with morning akinesia. Methods The safety population included 127 enrolled patients, and the full analysis set (FAS) included 88 patients. Patients completed…

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Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson’s disease patients

By Angelo Antonini MD, PhD,*, Victor S. C. Fung MBBS, PhD, FRACP, James T. Boyd MD, John T. Slevin MD, MBA, Coleen Hall MS, MBA, Krai Chatamra PhD, Susan Eaton PharmD and Janet A. Benesh BSMT

The purpose of this study was to assess the effect of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) in advanced Parkinson’s disease patients with troublesome dyskinesia.

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Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials

By Anthony E. Lang MD, FRCPC,*, Ramon L. Rodriguez MD, James T. Boyd MD, Sylvain Chouinard MD, FRCPC, Cindy Zadikoff MD, Alberto J. Espay MD, John T. Slevin MD, MBA, Hubert H. Fernandez MD, Mark F. Lew MD, David A. Stein MD, Per Odin MD, PhD, Victor S.C. Fung MBBS, PhD, FRACP, Fabian Klostermann MD, PhD, Alfonso Fasano MD, PhD, Peter V. Draganov MD, Nathan Schmulewitz MD, Weining Z. Robieson PhD, Susan Eaton PharmD, Krai Chatamra PhD, Janet A. Benesh BSMT and Jordan Dubow MD

Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.

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Apomorphine: A Potential Modifier of Amyloid Depositionin Parkinson’s Disease?

By Alison J. Yarnall MRCP, PhD, Tammaryn Lashley BSc, PhD, Helen Ling MRCP, PhD, Andrew J. Lees MD, FRCP, FMedSci, Shirley Y. Coleman MSc, PhD, Sean S. O'Sullivan MRCP, PhD, Yaroslau Compta MD, PhD, Tamas Revesz MD, FRCPath and David J. Burn MA, MD, FRCP*

Evidence from clinical and pathological studies suggests a role for both alpha-synuclein and amyloid-beta in the pathophysiology of dementia associated with PD. Recent work demonstrated improvement in memory and reduced amyloid-beta burden in transgenic murine Alzheimer’s models given subcutaneous apomorphine. The aim of this work was to determine whether antemortem exposure to apomorphine was associated with lower levels of amyloid-beta in brain tissue in a clinicopathological study of PD.

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Levodopa-carbidopa intestinal gel in advanced Parkinson’s disease: Final 12-month, open-label results

By Hubert H. Fernandez MD*, David G. Standaert MD, PhD*, Robert A. Hauser MD, Anthony E. Lang MD, FRCPC, Victor S.C. Fung PhD, FRACP, Fabian Klostermann PhD, Mark F. Lew MD, Per Odin MD, PhD, Malcolm Steiger MBBS, MD, FRCP, Eduard Z. Yakupov MD, PhD, DMSc, Sylvain Chouinard MD, FRCPC, Oksana Suchowersky MD, FRCPC, FCCMG, Jordan Dubow MD, Coleen M. Hall MS, Krai Chatamra PhD, Weining Z. Robieson PhD, Janet A. Benesh BSMT and Alberto J. Espay MD, MSc

Motor complications in Parkinson’s disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma–level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study…

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EuroInf: A Multicenter Comparative Observational Study of Apomorphine and Levodopa Infusion in Parkinson’s Disease

By Pablo Martinez-Martin MD, PhD, Prashanth Reddy MBBS, MRCP, Regina Katzenschlager MD, Angelo Antonini MD, PhD, Antoniya Todorova MD, PhD, Per Odin MD, PhD, Tove Henriksen MD, Anne Martin BSc, Daniela Calandrella MD, Alexandra Rizos MSc, Narissah Bryndum RN, Arne Glad RN, Haidar Salimi Dafsari MD, Lars Timmermann MD, Georg Ebersbach MD, Milica G. Kramberger MD, PhD, Michael Samuel MD, FRCP, Karoline Wenzel MD, Volker Tomantschger MD, Alexander Storch MD, Heinz Reichmann MD, Zvezdan Pirtosek MD, PhD, Maja Trost MD, PhD, Per Svenningsson MD, PhD, Sven Palhagen MD, Jens Volkmann MD, PhD and K. Ray Chaudhuri MD, DSc*

Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson’s disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared…

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Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease

By Rupam Borgohain DM*, Jozsef Szasz MD, Paolo Stanzione MD, Chandrashekhar Meshram DM, Mohit H. Bhatt DM, Dana Chirilineau MD, Fabrizio Stocchi MD, Valentina Lucini MD, Rodolfo Giuliani MD, Emma Forrest PhD, Patricia Rice PhD, Ravi Anand MD and the Study 018 Investigators

In a 6-month double-blind, placebo-controlled study of Parkinson’s disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months…

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Double-blind study of the actively transported levodopa prodrug XP21279 in Parkinson’s disease

By Peter A. LeWitt MD, MMSc*, F. Jacob Huff MD, Robert A. Hauser MD, MBA, Dan Chen MD, PhD, Dmitri Lissin MD, Katie Zomorodi PhD and Kenneth C. Cundy PhD

The objective of this study was to assess the efficacy, safety, and pharmacokinetics of XP21279-carbidopa in patients with Parkinson’s disease who experience motor fluctuations compared with immediate-release carbidopa-levodopa tablets. XP21279 is a levodopa prodrug that is actively absorbed by high-capacity nutrient transporters expressed throughout the gastrointestinal tract and then rapidly converted to levodopa by carboxylesterases. XP21279-carbidopa sustained-release bilayer tablets were developed to overcome pharmacokinetic limitations of levodopa by providing more continuous exposure…

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