image: Alberto Espay, MD
Credit: Photo/University of Cincinnati
An international, multisite phase 3 trial co-led by a University of Cincinnati researcher found Parkinson’s disease medication delivered through an infusion pump is safe and effective at reducing symptoms for longer periods of time.
These results, published March 15 in the Lancet Neurology journal, could lead to additional treatment options for patients with the condition.
Parkinson’s symptoms such as tremors, slowness and stiffness are caused by low levels of dopamine in the body. For decades, doctors have treated Parkinson’s by giving patients levodopa, the inactive substance in the brain that once converted makes dopamine.
“Levodopa is a replacement strategy. We all make levodopa, but Parkinson's patients make less of it,” said Espay, co-principal investigator of the trial, James J. and Joan A. Gardner Family Center for Parkinson’s Disease Research Endowed Chair in UC’s Department of Neurology and Rehabilitation Medicine and a physician at the UC Gardner Neuroscience Institute.
Espay said oral levodopa is effective and typically helps people regain normal motor function, but its benefits tend to last less than a few hours after a few years, requiring increases in doses or its frequency.
Levodopa is most commonly administered orally, but this trial tested continuous, 24-hour levodopa delivery through a subcutaneous infusion pump. A total of 381 patients with Parkinson’s disease in 16 countries enrolled in the trial and were randomized to receive levodopa through the infusion pump or through traditional oral medication.
The researchers found levodopa delivered through the infusion pump was safe and led to almost two hours of day (1.72) of additional “on time,” or the time when the medication is working and symptoms are lessened, compared to taking levodopa orally.
Espay said the results of this trial pave the way for this specific infusion pump delivery system to be approved by the Food and Drug Administration and other countries’ respective governing bodies.
“Once approved, this will become an important treatment strategy to consider for patients with Parkinson’s disease experiencing motor fluctuations not adequately controlled with medication,” he said. “Future studies will need to determine the durability of the long-term benefits and whether any safety issues could emerge, as well as how it might compare with deep brain stimulation.”
Two additional subcutaneous delivery systems are also expected to be approved this year, Espay said, and researchers are continuing to study how to improve levodopa formulations and delivery to optimize its effect for patients.
“Levodopa delivery systems are expected to continue to improve over time,” he said. “This is a thriving area of research for the benefits of our patients.”
The trial was funded by NeuroDerm
Journal
The Lancet Neurology
Method of Research
Randomized controlled/clinical trial
Subject of Research
People
Article Title
Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson’s disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial
Article Publication Date
15-Mar-2024
COI Statement
AJE, FS, RP, AA, AE, JJF, NG, TG, SH-B, JH-V, SHI, KK, PAL, LL-M, WP, HS, and OR were investigators in the study and they or their institution received fees for participation. CWO and KK have stock ownership in Clintrex, which was contracted by NeuroDerm to provide services for this study. TY, LA, LS, NL, and NS are employed by NeuroDerm. RC was employed by NeuroDerm at the time of the study and is now employed by Mitsubishi Tanabe Pharma America. AJE has received grant support from the National Institutes of Health and the Michael J Fox Foundation; personal compensation as a consultant or scientific advisory board member for NeuroDerm, Herantis Pharma, Amneal, Acadia, Acorda, Kyowa Kirin, Sunovion, and Supernus; personal compensation as honoraria for speakership for Avion; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. AJE cofounded REGAIN Therapeutics (a biotech startup developing non-aggregating peptide analogues as replacement therapies for neurodegenerative diseases) and is co-owner of a patent that covers synthetic soluble non-aggregating peptide analogues as replacement treatments in proteinopathies. FS reports honoraria and consulting fees from BIAL, Sunovion, AbbVie, Luosofarmaco, Kyowa, Synagile, Lundbeck, TEVA, UCB, Zambon, Blue Rock, NeuroDerm, Contera, Zambon, Biogen, Ever, and Britannia; speaker fees from BIAL, Sunovion, AbbVie, Luosofarmaco, Kjowa, Synagile, Lundbeck, TEVA, UCB, and Zambon; and travel support from Bial, Zambon, Synagile, and AbbVie. RP reports grants from Abbott, AbbVie, Alexza, Annovis, Biogen, Bluerock, Bukwang, Cerevel, Global Kinetics, Jazz, the Michael J Fox Foundation, NeuroDerm, Neuraly, the Parkinson’s Foundation, Praxis, Roche, Sage, Scion, Sun Pharma, UCB, and Voyager; and consulting fees from Abbott, AbbVie, ACADIA, Acorda, Allevion, Amneal, Artemida, BioVie, CalaHealth, Convatec, Global Kinetics, Inbeeo, Insightec, Jazz, Kyowa, Lundbeck, Merz, Neurocrine, NeuroDerm, Ono, PhotoPharmics, Sage, Sunovion, BioVie, Cerevel, Ipsen, Mitsubishi Tanabe Pharma America, NeuroDerm, Praxis, Revance, Supernus, Teva, US WorldMeds, and XW Labs. JJF has provided consultancy for AbbVie, BIAL, Biogen, Lundbeck, and Sunovion; received grants from Angelini, Novartis, Medtronic, AbbVie, Zambon, BIAL, Biogen, and Grunenthal; and received speaker fees for BIAL, Ono, SK Chemical, and Infucure. NG serves as consultant to NeuroDerm, Sanofi, and Biogen. NG also reports payment for lectures, travel support, or both from BIAL, NeuroDerm, and Biogen; stock options in Vibrant and Longevity AI; and a patent pending for GaitBetter. TG has served as consultant to NeuroDerm, AbbVie, Medisson, Truemed, and Tradis Gat; has received research support from the Movement Disorders Society; and has received the Center of Excellence grant from the Parkinson’s Foundation. TG reports fees for lectures, travel support, or both from AbbVie, Medisson, Teva, Boston Scientific, and Alphamedix; stock options in Cytora and Neurosteer; and a patent for an automated analysis of speech and development of vocal biomarkers in Parkinson’s disease. SH-B serves as consultant to NeuroDerm, AbbVie, Teva, Takeda, Medison, Trumed, and Abbott; has received payment for lectures from AbbVie, Medisson, and Teva; and has received research support from AbbVie and the Michael J Fox Foundation. JH-V reports grants from Fondo de Investigación Sanitaria; honoraria for lectures, travel support, or both from BIAL, Zambon, Italfarmaco, and AbbVie; and stock in Sense4care. SHI reports honoraria for CME, consultant fees, research grants, or promotional speaker fees on behalf of AbbVie, Acadia, Acorda, Adamas, Addex, Affiris, Alexva, Allergan, Amarantus, Amneal, Aptinyx, Axial, Axovant, Benevolent, Biogen, Britannia, Cadent, Cala, Cerecor, Cerevel, Cipla, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Impel, Intec Pharma, Ipsen, Jazz, Kyowa, Lundbeck, Merz, the Michael J Fox Foundation, Mitsubishi Tanabe, Neuralys, Neurocrine, NeuroDerm, Parkinson Study Group, Pharma2B, Prilenia, Promentis, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Supernus, Teva, Theravance, UCB, and Zambon. KK reports equity interest in Clintrex and Hoover Brown; patents for information management; and participation in safety monitoring boards for Roche, Lilly, and Janssen. PAL reports advisory roles for Abide, Acorda Therapeutics, Adamas, Amneal, Aptinyx, Biogen, Britannia, Bukwang Pharma, Cavion, Cerevel, Denali, F Hoffmann–La Roche, Jazz Pharmaceuticals, Kyowa Kirin Hakko, Neurocrine, Mitsubishi NeuroDerm, Sage, Supernus, and US WorldMeds; and research grant support from the Michael J Fox Foundation, NeuroDerm, Parkinson Study Group, Pharma Two B, Hoffmann–La Roche, Sunovion, Sun Pharma, and US WorldMeds. CWO reports equity interest in Clintrex and expert witness testimony in the Paraquat litigation. WP has received lecture fees and honoraria for consultancy in relation to clinical drug development programs from AbbVie, AC Immune, Alterity, BIAL, Boehringer, Britannia, Lilly, Eisai, Lundbeck, Roche, Takeda, Britannia, Eisai, Roche, Stada, and Zambon; grant support from the Michael J Fox Foundation and the EU FP7 & Horizon 2020 programs; and safety monitoring board membership for UCB. WP also reports leadership roles in the Movement Disorder Society, Austrian Society of Neurology, and Austrian Parkinson’s disease Society. HS reports consultancy fees from Novo Nordisk, Blue Rock Therapeutics, and Neurocrine; clinical trial support from Insightec, Sun Pharmaceuticals, Prevail Therapeutics, Blue Rock Therapeutics, Novo Nordisk, Biogen, Genentech–Roche, Bukwang, and the National Institutes of Health. OR has participated in advisory boards or provided consultancy for AbbVie, Adamas, Acorda, Addex, AlzProtect, ApoPharma, AstraZeneca, Axovant, Bial, Biogen, Britannia, Buckwang, CereSpir, Clevexel, Denali, INC Research, IPMDS, Lundbeck, Lupin, Merck, MundiPharma, NeurATRIS, NeuroDerm, Novartis, ONO Pharma, Osmotica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Roche, Sanofi, Servier, Sunovion, Theranexus, Takeda, Teva, UCB, Vectura, Watermark Research, XenoPort, XO, and Zambon; and has received grants from Agence Nationale de la Recherche, CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, the Michael J Fox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7 and H2020), 1 16 and Cure Parkinson’s.