Subcutaneous Levodopa Infusion for Parkinson's Disease: 1<scp>‐Year</scp> Data from the <scp>Open‐Label BeyoND</scp> Study

Poewe, Werner; Stocchi, Fabrizio; Arkadir, David; Ebersbach, Georg; Ellenbogen, Aaron; Giladi, Nir; Isaacson, Stuart; Kieburtz, Karl; LeWitt, Peter A.; Olanow, C. Warren; Simuni, Tanya; Thomas, Astrid; Zlotogorski, Abraham; Adar, Liat; Case, Ryan; Oren, Sheila; Orenbach, Shir Fuchs; Rosenfeld, Olivia; Sasson, Nissim; Yardeni, T.; Espay, Alberto J.

doi:10.1002/mds.28758

Cited by 26 publications

(25 citation statements)

References 14 publications

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“…Evaluations of pain did not indicate any severe discomfort (pain or pruritus) associated with the nodules or any other infusion site findings. As was reported in the one year study with higher dosing regimens of ND0612, the observed nodules were generally manageable and were not a cause for discontinuation from the study [29]. However, it should be noted that this early proof of concept study employed a lower dose, and therefore smaller total volume than the dosing regiments currently being tested.…”

Section: Discussionsupporting

confidence: 58%

“…At the low dose used in this study, ND0612 was generally welltolerated and there were no TEAEs of dyskinesia or psychiatric symptoms reported in these patients already on long-term (mean > 7 years) levodopa therapy. In line with one year safety observations of the higher ND0612 dosing regimens currently in development [29], most patients treated with ND0612 developed transient nodules. These ISR are generally expected with SC infusion of drugs [30][31][32] and some skin reactions were also observed with placebo (saline) administration, which may be connected to the SC needle insertions.…”

Section: Discussionmentioning

confidence: 55%

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ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study

Giladi

Gurevich

Djaldetti

et al. 2021

Parkinsonism & Related Disorders

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Introduction: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations. Methods: This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC. During Period-2, 16 patients were randomized to receive 7 days treatment with ND0612 or ND0612 plus oral entacapone. Reduction in OFF time was analyzed as an exploratory measure using a futility design with a predefined margin of 1.6 h. Results: ND0612 was well-tolerated; most patients experienced infusion site nodules (95% vs. 56% with placebo), which all resolved without sequelae. Patients treated with adjunct ND0612 during Period-1 avoided deep troughs in levodopa plasma levels and had a decreased fluctuation index versus placebo (1.6 ± 0.5 vs 3.1 ± 1.6 at end of Period-1, respectively). In Period-2, the coadministration of entacapone with continuous ND0612 SC infusion translated to an increase in mean levodopa AUC 0-10h compared to baseline. Exploratory efficacy analysis of Period 1 showed mean ± SD OFF time reductions of − 2.13 ± 2.24 [90%CI: -2.8, ∞] hours (p = 0.84 using H 0 of μ 0 ≤-1.6). Conclusion:Levodopa/carbidopa infusion with ND0612 was generally well-tolerated and resulted in reduced fluctuations in plasma levodopa concentrations when given with SoC oral levodopa. ND0612 met the efficacy endpoint for the futility design.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 55%

ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study

Giladi

Gurevich

Djaldetti

et al. 2021

Parkinsonism & Related Disorders

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“…Additionally, data from an open-label (BeyoND) study demonstrated safety with a nominally significant increase in good ON time (defined as the sum of ON-WoTD and ON time with non-troublesome dyskinesia). A treatment-emergent adverse event and common reason for discontinuation is infusion site reactions (ISRs) [ 111 , 112 ]. The long-term safety data highlighted that such ISRs are frequently mild, reversible, and could be minimized with continued training.…”

Section: Motor Fluctuationsmentioning

confidence: 99%

Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease

Luca

Reyes

Fox

2022

Drugs

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Motor symptoms are a core feature of Parkinson’s disease (PD) and cause a significant burden on patients’ quality of life. Oral levodopa is still the most effective treatment, however, the motor benefits are countered by inherent pharmacologic limitations of the drug. Additionally, with disease progression, chronic levodopa leads to the appearance of motor complications including motor fluctuations and dyskinesia. Furthermore, several motor abnormalities of posture, balance, and gait may become less responsive to levodopa. With these unmet needs and our evolving understanding of the neuroanatomic and pathophysiologic underpinnings of PD, several advances have been made in defining new therapies for motor symptoms. These include newer levodopa formulations and drug delivery systems, refinements in adjunctive medications, and non-dopaminergic treatment strategies. Although some are in early stages of development, these novel treatments potentially widen the available options for the management of motor symptoms allowing clinicians to provide an individually tailored care for PD patients. Here, we review the existing and emerging interventions for PD with focus on newly approved and investigational drugs for motor symptoms, motor fluctuations, dyskinesia, and balance and gait dysfunction.

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“…Therefore, subcutaneous administration might both avoid fluctuations in absorption resulting from delayed gastric emptying and reduce surgical risks compared to Duodopa ® ( Nilsson et al, 1998 ; Nyholm and Lennernas, 2008 ). Poewe et al (2021) evaluated the 1-year safety data of ND0612. After evaluation by 214 patients, most patients experienced infusion site reactions such as particularly nodules (30.8%) and hematomas (25.2%).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Devices for Motor Symptoms in Parkinson’s Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials

Fujikawa

Morigaki

Yamamoto

et al. 2022

Front. Aging Neurosci.

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BackgroundPharmacotherapy is the first-line treatment option for Parkinson’s disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson’s disease.MethodsWe first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices.ResultsOur review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark.ConclusionInvasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.

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Subcutaneous Levodopa Infusion for Parkinson's Disease: 1‐Year Data from the Open‐Label BeyoND Study

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 26 publications

References 14 publications

ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study

ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study

Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease

Therapeutic Devices for Motor Symptoms in Parkinson’s Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials

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