Feasibility of home dose optimization of apomorphine sublingual film in Parkinson's disease patients with OFF episodes: results from the dose-optimization phase of an open-label, randomized crossover study.

"Declarations Ethics approval and consent to participate: The study was designed, conducted, and monitored in accordance with the World Medical Association Declaration of Helsinki (1989) and International Council for Harmonization guidelines. The study protocol and study procedures were approved by central institutional review boards (Medical University of Innsbruck Ethics Committee, Austria [Approval ID: ECno: 1218/2017]; Comité de Protection des Personnes du Sud-Ouest et Outre-Mer IV, France [Approval ID: CPP17-087a/2016-003456-70]; Ulm University Ethics Committee, Germany [Approval ID: 446/17 – FSt/se]; Fundació de Gestió Sanitària of the Hospital de la Santa Creu i Sant Pau, Spain [Approval ID: HSCSP REF. No.: 17/320]; Dulwich Research Ethics Committee Health Research Authority, UK [Approval ID: REC reference 17/LO/0232]; Health Research Authority, UK [Approval ID: REC reference 17/LO/0232]) and independent ethics committees before enrollment of any patients into the study. All patients provided written informed consent to participate.Consent for publication: Not applicable.Author contributions:Jan Kassubek: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Fabrizio Stocchi: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Ernest Balaguer Martinez: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Rajesh Pahwa: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.William Ondo: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Yi Zhang: Conceptualization; Data curation; Formal analysis; Writing – original draft; Writing – review & editing.Alyssa Bowling: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Eric Pappert: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Stuart Isaacson: Conceptualization; Data curation; Writing – original draft; Writing – review & editing.Stacy Wu: Conceptualization; Data curation; Formal analysis; Writing – original draft; Writing – review & editing.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by funding from Sunovion Pharmaceuticals Inc. (Marlborough, MA, USA) and both current and former employees of Sunovion Pharmaceuticals Inc. were involved in the study design and interpretation of its results. Medical writing and editorial assistance for the development of this manuscript were funded by Sunovion Pharmaceuticals Inc. (Marlborough, MA, USA) and BIAL–Portela & Cª, S.A., Coronado, Portugal.Competing interests: JK has received honoraria or consultation fees from AbbVie, Bial, Biogen, Desitin, Esteve, Licher MT, Medtronic, NeuroDerm, Novartis, STADA, UCB Pharma, and Zambon; in addition, he is Specialty Chief Editor for Frontiers in Neurology (section Applied Neuroimaging) and Associate Editor (Neurology) for Therapeutic Advances in Chronic Disease. FS reports grants and/or research support from Zambon and honoraria or consultation fees from Bial, Biogen, Britannia Pharmaceuticals, Chiesi, Cynapsus Therapeutics, Kyowa Kirin, Lundbeck, NeuroDerm, Sunovion Pharmaceuticals Inc., and Zambon. EBM is Director of Research at Hospital Universitari General de Catalunya and signs agreements with the hospital to perform clinical trials. RP reports honoraria, consultant fees, and/or research grants from Abbott Laboratories, AbbVie, Acadia Pharmaceuticals Inc., Acorda Therapeutics, Inc., Adamas Pharmaceuticals, Inc., Amneal Pharmaceuticals LLC, Biogen, Biohaven Pharmaceuticals Inc, Boston Scientific, Cala Health, EIP Pharma, Inc., Eli Lilly, Global Kinetics Pty Ltd, Kyowa Kirin, Lundbeck, Mitsubishi Tanabe Pharma America, Neuraly Inc, Neurocrine Biosciences, Parkinson Foundation, Pharma Two B Ltd., Prilenia Therapeutics, Roche, Sage Therapeutics, Sun Pharma, Sunovion Pharmaceuticals Inc., Theranexus, Theravance Biopharma, US WorldMeds LLC, and Voyager. WO reports honoraria, consultant fees, and/or research grants from ACADIA, Acorda, Allergan, Amneal, Biogen, Cerevel, Dystonia Coalition (NIH), Emalex, Harmony, Jazz, Kyowa Kirin, Merz, Neurocrine, Restless Legs Syndrome Foundation, Sage, SCION, Sun, Sunovion, Supernus, TEVA, XWPharma, and royalties from the books Movement Disorders in Psychiatry, and UpToDate. YZ, AB, and EP were employees of Sunovion Pharmaceuticals Inc. at the time the analyses were conducted. SI reports honoraria for CME, consultancy, research grants, and/or promotional speaker work on behalf of AbbVie, Acadia Pharmaceuticals Inc, Acorda Therapeutics Inc, Adamas Pharmaceuticals, Inc., Addex Therapeutics, AFFiRiS AG, Alexza Pharmaceuticals, Allergan, Amarantus BioScience, Amneal Pharmaceuticals, Aptinyx, Axial Therapeutics, Inc., Axovant Gene Therapies, BenevolentAI, Biogen, Britannia Pharmaceuticals, Cadent Therapeutics, Cala Health, Cerecor, Inc, Cerevel Therapeutics, Cipla, Eli Lilly, Enterin Inc., GE HealthCare, Global Kinetics Pty Ltd, Impax Laboratories, Impel NeuroPharma, Intec Pharma, Ipsen, Jazz Pharmaceuticals, Kyowa Kirin, Lundbeck, Merz Pharmaceuticals, Michael J. Fox Foundation, Mitsubishi Tanabe Pharma, Neuraly, Neurocrine Biosciences, NeuroDerm, Parkinson Study Group, Pharma Two B, Prilenia Therapeutics, Promentis Pharmaceuticals, Inc., Revance, Roche, Sanofi, Sunovion Pharmaceuticals Inc., Sun Pharma, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theravance Biopharma, and UCB. SW is an employee of Sumitomo Pharma America. On July 1, Sunovion and other US subsidiaries were consolidated into Sumitomo Pharma America.Availability of data and materials: The dataset analyzed in this study is included in the manuscript and the supplementary material. Competing interests: JK has received honoraria or consultation fees from AbbVie, Bial, Biogen, Desitin, Esteve, Licher MT, Medtronic, NeuroDerm, Novartis, STADA, UCB Pharma, and Zambon; in addition, he is Specialty Chief Editor for Frontiers in Neurology (section Applied Neuroimaging) and Associate Editor (Neurology) for Therapeutic Advances in Chronic Disease. FS reports grants and/or research support from Zambon and honoraria or consultation fees from Bial, Biogen, Britannia Pharmaceuticals, Chiesi, Cynapsus Therapeutics, Kyowa Kirin, Lundbeck, NeuroDerm, Sunovion Pharmaceuticals Inc., and Zambon. EBM is Director of Research at Hospital Universitari General de Catalunya and signs agreements with the hospital to perform clinical trials. RP reports honoraria, consultant fees, and/or research grants from Abbott Laboratories, AbbVie, Acadia Pharmaceuticals Inc., Acorda Therapeutics, Inc., Adamas Pharmaceuticals, Inc., Amneal Pharmaceuticals LLC, Biogen, Biohaven Pharmaceuticals Inc, Boston Scientific, Cala Health, EIP Pharma, Inc., Eli Lilly, Global Kinetics Pty Ltd, Kyowa Kirin, Lundbeck, Mitsubishi Tanabe Pharma America, Neuraly Inc, Neurocrine Biosciences, Parkinson Foundation, Pharma Two B Ltd., Prilenia Therapeutics, Roche, Sage Therapeutics, Sun Pharma, Sunovion Pharmaceuticals Inc., Theranexus, Theravance Biopharma, US WorldMeds LLC, and Voyager. WO reports honoraria, consultant fees, and/or research grants from ACADIA, Acorda, Allergan, Amneal, Biogen, Cerevel, Dystonia Coalition (NIH), Emalex, Harmony, Jazz, Kyowa Kirin, Merz, Neurocrine, Restless Legs Syndrome Foundation, Sage, SCION, Sun, Sunovion, Supernus, TEVA, XWPharma, and royalties from the books Movement Disorders in Psychiatry, and UpToDate. YZ, AB, and EP were employees of Sunovion Pharmaceuticals Inc. at the time the analyses were conducted. SI reports honoraria for CME, consultancy, research grants, and/or promotional speaker work on behalf of AbbVie, Acadia Pharmaceuticals Inc, Acorda Therapeutics Inc, Adamas Pharmaceuticals, Inc., Addex Therapeutics, AFFiRiS AG, Alexza Pharmaceuticals, Allergan, Amarantus BioScience, Amneal Pharmaceuticals, Aptinyx, Axial Therapeutics, Inc., Axovant Gene Therapies, BenevolentAI, Biogen, Britannia Pharmaceuticals, Cadent Therapeutics, Cala Health, Cerecor, Inc, Cerevel Therapeutics, Cipla, Eli Lilly, Enterin Inc., GE HealthCare, Global Kinetics Pty Ltd, Impax Laboratories, Impel NeuroPharma, Intec Pharma, Ipsen, Jazz Pharmaceuticals, Kyowa Kirin, Lundbeck, Merz Pharmaceuticals, Michael J. Fox Foundation, Mitsubishi Tanabe Pharma, Neuraly, Neurocrine Biosciences, NeuroDerm, Parkinson Study Group, Pharma Two B, Prilenia Therapeutics, Promentis Pharmaceuticals, Inc., Revance, Roche, Sanofi, Sunovion Pharmaceuticals Inc., Sun Pharma, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theravance Biopharma, and UCB. SW is an employee of Sumitomo Pharma America. On July 1, Sunovion and other US subsidiaries were consolidated into Sumitomo Pharma America."

"Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by funding from Sunovion Pharmaceuticals Inc. (Marlborough, MA, USA) and both current and former employees of Sunovion Pharmaceuticals Inc. were involved in the study design and interpretation of its results. Medical writing and editorial assistance for the development of this manuscript were funded by Sunovion Pharmaceuticals Inc. (Marlborough, MA, USA) and BIAL–Portela & Cª, S.A., Coronado, Portugal."

"Trial registration: This study is registered with EudraCT (2016-003456-7): Clinical Trials register – Search for eudract_number:2016-003456-70."