The purpose of the study is to assess the efficacy and safety of XP21279/Carbidopa in comparison to Sinemet as well as evaluate the pharmacokinetics (PK) of levodopa after administration of XP21279/Carbidopa and Sinemet and to explore exposure-response relationships in a subset of subjects.

开始日期2010-07-01

申办/合作机构

XenoPort, Inc.

NCT00914602 / Completed临床1/2期

An Exploratory Pharmacokinetic, Pharmacodynamic and Safety Study of XP21279 (With Lodosyn®) and Sinemet® in Parkinson's Disease Subjects With Motor Fluctuations

The purpose of the study is to assess the pharmacokinetics, pharmacodynamics, and safety of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease with Motor Fluctuations.

开始日期2009-05-01

申办/合作机构

XenoPort, Inc.

100 项与 XP-21279 相关的临床结果

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100 项与 XP-21279 相关的转化医学

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100 项与 XP-21279 相关的专利（医药）

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项与 XP-21279 相关的文献（医药）

2016-11-01·CNS Drugs2区 · 医学

Novel Levodopa Formulations for Parkinson’s Disease

2区 · 医学

Review

作者: Ruiz-Lopez, Marta ; Freitas, Maria Eliza ; Fox, Susan H

Levodopa remains the most effective treatment for Parkinson's disease and is considered the gold standard therapy. However, disease progression and changes in the gastrointestinal tract result in a declining window of treatment response in a majority of patients. Efforts have been made recently to improve levodopa bioavailability either by developing more effective oral formulations or by innovating routes of administration (intestinal infusion, transcutaneous or inhaled levodopa). IPX066 is a novel levodopa-carbidopa (LD/CD) oral formulation combining immediate-release (IR) and extended-release (ER) LD/CD recently approved in the USA and the EU. Levodopa-carbidopa intestinal gel (LCIG) is an approved therapy consisting of a suspension of levodopa and carbidopa infused directly into the proximal jejunum via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube through a portable infusion pump. Ongoing studies are evaluating the 'accordion pill' (AP09004), an ER LD/CD formulation with gastroretentive properties. ND0612 is a proprietary liquid formulation of LD/CD that enables subcutaneous administration via a small patch-pump device, and CVT-301 is a levodopa inhalation powder with rapid onset of action; both are currently in active studies. Other novel formulations have been discontinued, including DM-1992, which is a bilayer formulation containing an IR LD/CD layer and an ER LD/CD layer with gastroretentive properties, and XP21279, a novel oral levodopa prodrug that is absorbed from the small and large intestine by high-capacity nutrient transporters expressed throughout the gastrointestinal system. ODM-101 is a new oral formulation of levodopa/carbidopa/entacapone that contains a higher amount of carbidopa (65 or 105 mg), but no active studies are underway. The current review aims to summarize the pharmacokinetic aspects, clinical efficacy, and potential adverse events of novel levodopa formulations currently available or under development.

2015-01-01·Movement Disorders1区 · 医学

Novel formulations and modes of delivery of levodopa

1区 · 医学

Review

作者: Poewe, Werner ; Antonini, Angelo

ABSTRACTEver since its early clinical use in the 1960s, levodopa has remained the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Motor response fluctuations and drug‐induced dyskinesias seriously compromise the unparalleled symptomatic efficacy ofl‐dopa during long‐term treatment. Discontinuous drug delivery resulting from the short half‐life ofl‐dopa and erratic gastrointestinal absorption plays a major role in the pathophysiology of these motor complications. Several approaches to improve the pharmacokinetics and ways of administration ofl‐dopa are in different stages of clinical development and include novel formulations as well as nonoral routes of drug delivery. IPX066 is a novel extended‐releasel‐dopa capsule that has successfully completed phase III clinical trials while thel‐dopa prodrug XP21279 and a gastric retention formulation (“accordion pill”) are in earlier phases of clinical development. Novel enzyme inhibitors enhancingl‐dopa efficacy and half‐life are also still being developed, including a novel catechol‐O‐methyltransferase inhibitor with once‐daily pharmacokinetics, and there are studies testing the effects of increasing the dose of amino acid decarboxylase inhibitors given concomitantly withl‐dopa. Intrajejunal infusion of a gel formulation ofl‐dopa/carbidopa is in clinical use in Europe, and its efficacy to smooth out motor fluctuations has recently been shown in a randomized, controlled trial. Subcutaneous and intrapulmonal delivery routes ofl‐dopa have reached phase III of clinical development. After more than 50 years of clinical use,l‐dopa not only remains the gold standard of symptomatic efficacy, but it also remains a drug in active clinical development. © 2014 International Parkinson and Movement Disorder Society

2014-01-01·Movement Disorders1区 · 医学

Double‐blind study of the actively transported levodopa prodrug XP21279 in Parkinson's disease

1区 · 医学

Article

作者: Zomorodi, Katie ; Huff, F. Jacob ; Chen, Dan ; Lissin, Dmitri ; Hauser, Robert A. ; Cundy, Kenneth C. ; LeWitt, Peter A.

ABSTRACTThe 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. Patients with motor fluctuations who required carbidopa‐levodopa four or five times daily were optimized for 2 weeks each on carbidopa‐levodopa four or five times daily and XP21279‐carbidopa three times daily in a randomized sequence. Next, they received each optimized treatment for 2 weeks in a double‐blind/double‐dummy, randomized sequence. The primary outcome measure was change from baseline in daily off time at the end of each double‐blind treatment period. All patients at 2 sites underwent pharmacokinetic analyses. Twenty‐eight of 35 enrolled patients completed both double‐blind treatments. The mean total daily off time was reduced from baseline by a mean (± standard error) of 2.7 hours (± 0.48 hours) for immediate‐release carbidopa‐levodopa and 3.0 hours (± 0.57 hours) for XP21279‐carbidopa (P = 0.49). Among 11 patients who completed pharmacokinetic sampling on each optimized treatment, the percentage deviation from the mean levodopa concentration was lower (P < 0.05) for XP21279‐carbidopa than carbidopa‐levodopa. Both treatments had a similar incidence of new or worsening dyskinesias. XP21279‐carbidopa administered three times daily produced a reduction in off time similar to that of carbidopa‐levodopa administered four or five times daily, and the difference was not statistically significant. XP21279‐carbidopa significantly reduced variability in levodopa concentrations compared with carbidopa‐levodopa. © 2013 International Parkinson and Movement Disorder Society

100 项与 XP-21279 相关的药物交易

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