Long-Term Treatment with Extended-Release Carbidopa– Levodopa (IPX066) in Early and Advanced Parkinson’s Disease: A 9-Month Open-Label Extension Trial

Background and Objective IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD). Methods Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. Results Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to *500 and *1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension. Conclusion During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy

Long-term treatment with extended-release carbidopa-levodopa (IPX066) in early and advanced Parkinson's Disease : a 9-month open-label extension trial

Background and Objective IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD). Methods Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. Results Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to *500 and *1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension. Conclusion During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy

Quantitative Analysis of Tremors in Welders

Background: Workers chronically exposed to manganese in welding fumes may develop an extra-pyramidal syndrome with postural and action tremors. Objectives: To determine the utility of tremor analysis in distinguishing tremors among workers exposed to welding fumes, patients with Idiopathic Parkinson’s Disease (IPD) and Essential Tremor (ET). Methods: Retrospective study of recorded tremor in subjects from academic Movement Disorders Clinics and Welders. Quantitative tremor analysis was performed and associated with clinical status. Results: Postural tremor intensity was increased in Welders and ET and was associated with visibly greater amplitude of tremor with arms extended. Mean center frequencies (Cf) of welders and patients with ET were significantly higher than the mean Cf of PD subjects. Although both the welders and the ET group exhibited a higher Cf with arms extended, welders could be distinguished from the ET subjects by a significantly lower Cf of the rest tremor than that measured in ET subjects. Conclusions: In the context of an appropriate exposure history and neurological examination, tremor analysis may be useful in the diagnosis of manganese-related extra-pyramidal manifestations