PMID- 33486139 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20211227 IS - 1873-5126 (Electronic) IS - 1353-8020 (Linking) VI - 83 DP - 2021 Feb TI - Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study. PG - 79-85 LID - S1353-8020(21)00016-X [pii] LID - 10.1016/j.parkreldis.2020.12.024 [doi] AB - INTRODUCTION: The randomized, double-blind phase (DBP) of the TOLEDO study confirmed the efficacy of apomorphine infusion (APO) in reducing OFF time in PD patients with persistent motor fluctuations despite optimized oral/transdermal therapy. Here we report safety and efficacy results including the 52-week open-label phase (OLP). METHODS: All patients completing the 12-week DBP (including those switching early to open-label treatment) were offered OLP entry. The primary objective was the evaluation of long-term safety of APO. RESULTS: Eighty-four patients entered the OLP (40 previously on APO, 44 on placebo) and 59 patients (70.2%) completed the study. The safety profile of APO was consistent with experience from extensive clinical use. Common treatment-related adverse events (AEs) were mild or moderate infusion site nodules, somnolence and nausea. Fourteen (16.7%) patients discontinued the OLP due to AEs, those involving >1 patient were infusion site reactions (n = 4) and fatigue (n = 2); hemolytic anemia occurred in one case. Reduction in daily OFF time and improvement in ON time without troublesome dyskinesia were sustained for up to 64 weeks. Pooled data for week 64 (n = 55) showed a mean (SD) change from DBP baseline in daily OFF time of -3.66 (2.72) hours and in ON time without troublesome dyskinesia of 3.31 (3.12) hours. Mean (+/-SD) daily levodopa-equivalent dose decreased from DBP baseline to week 64 by 543 mg (+/-674) and levodopa dose by 273 mg (+/-515). CONCLUSIONS: The safety and efficacy of APO infusion were demonstrated with long-term use for persistent motor fluctuations, allowing substantial reductions in oral PD medication. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Katzenschlager, Regina AU - Katzenschlager R AD - Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria. Electronic address: regina.katzenschlager@gesundheitsverbund.at. FAU - Poewe, Werner AU - Poewe W AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. Electronic address: Werner.Poewe@i-med.ac.at. FAU - Rascol, Olivier AU - Rascol O AD - Universite de Toulouse 3, INSERM, CHU de Toulouse, Centre D'Investigation Clinique CIC1436, Reseau NS-PARK/F-CRIN, Centre Expert Parkinson de Toulouse, Centre COEN NeuroToul, Department of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, Toulouse, France. Electronic address: olivier.rascol@univ-tlse3.fr. FAU - Trenkwalder, Claudia AU - Trenkwalder C AD - Department of Neurosurgery, University Medical Centre Goettingen and Centre of Parkinsonism and Movement Disorders, Elena Hospital, Kassel, Germany. Electronic address: claudia.trenkwalder@med.uni-goettingen.de. FAU - Deuschl, Gunther AU - Deuschl G AD - Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Christian-Albrechts University, Kiel, Germany. Electronic address: g.deuschl@neurologie.uni-kiel.de. FAU - Chaudhuri, K Ray AU - Chaudhuri KR AD - Parkinson Foundation Centre of Excellence, Kings College Hospital, Denmark Hill Campus, London, UK. Electronic address: ray.chaudhuri@kcl.ac.uk. FAU - Henriksen, Tove AU - Henriksen T AD - Movement Disorder Clinic, Bispebjerg Hospital, Copenhagen, Denmark. Electronic address: tovehenriksen@dadlnet.dk. FAU - van Laar, Teus AU - van Laar T AD - Department of Neurology, University Medical Centre, Groningen, the Netherlands. Electronic address: t.van.laar@umcg.nl. FAU - Lockhart, Donna AU - Lockhart D AD - Britannia Pharmaceuticals Limited, Reading, UK. Electronic address: donnamcvey@hurstgrangeassociates.co.uk. FAU - Staines, Harry AU - Staines H AD - Sigma Statistical Services, Balmullo, UK. Electronic address: harry.staines@britannia-pharm.com. FAU - Lees, Andrew AU - Lees A AD - University College London Institute of Neurology, Queen Square, London, UK. Electronic address: andrew.lees@ucl.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT02006121 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210112 PL - England TA - Parkinsonism Relat Disord JT - Parkinsonism & related disorders JID - 9513583 RN - 0 (Dopamine Agonists) RN - N21FAR7B4S (Apomorphine) SB - IM MH - Aged MH - Apomorphine/administration & dosage/adverse effects/*pharmacology MH - Dopamine Agonists/administration & dosage/adverse effects/*pharmacology MH - Double-Blind Method MH - *Drug-Related Side Effects and Adverse Reactions MH - Dyskinesia, Drug-Induced/etiology MH - Female MH - Humans MH - Infusions, Subcutaneous MH - Male MH - Middle Aged MH - Outcome Assessment, Health Care MH - Parkinson Disease/*drug therapy OTO - NOTNLM OT - Apomorphine subcutaneous infusion OT - Dyskinesia OT - Motor fluctuations OT - OFF time OT - Parkinson's disease OT - Safety OT - Tolerability EDAT- 2021/01/25 06:00 MHDA- 2021/12/28 06:00 CRDT- 2021/01/24 20:36 PHST- 2020/06/14 00:00 [received] PHST- 2020/10/29 00:00 [revised] PHST- 2020/12/22 00:00 [accepted] PHST- 2021/01/25 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2021/01/24 20:36 [entrez] AID - S1353-8020(21)00016-X [pii] AID - 10.1016/j.parkreldis.2020.12.024 [doi] PST - ppublish SO - Parkinsonism Relat Disord. 2021 Feb;83:79-85. doi: 10.1016/j.parkreldis.2020.12.024. Epub 2021 Jan 12.