Ipx066

Background: IPX066 is an extended-release (ER) oral formulation of carbidopa-levodopa (CD-LD). Following an initial peak at about one hour, plasma LD concentrations are maintained for about 4-5 hours. Objective: To present dosing factors that may affect the successful conversion to ER CD-LD from other LD formulations. Methods: Two-phase 3 studies of ER CD-LD vs. immediate-release (IR) CD-LD (ADVANCE-PD) and vs. CD-LD + entacapone (CLE; ASCEND-PD) in subjects with advanced PD included a 6-week, open-label conversion to ER CD-LD prior to treatment randomization...

Levodopa is the most efficacious and best-tolerated drug for treating Parkinson's disease (PD). To improve the treatment of PD, recent research initiatives have aimed to optimize the pharmacokinetic plasma behavior of L-dopa. Areas covered: This non-systematic, narrative drug evaluation brings the therapeutic value of IPX066 up for discussion. IPX066 is an orally applied levodopa/carbidopa containing formulation with modified drug release. It is rapidly absorbed, similar to conventional immediate-release levodopa preparations...

Background: In patients with Parkinson's disease (PD), oral dosing of extended-release carbidopa-levodopa (Rytary, IPX066 [ER CD-LD]) achieves peak levodopa plasma concentrations within 1 hour and maintains them for 4-6 hours. Aims: To compare the onset and duration of ER CD-LD benefit with those of immediate-release carbidopa-levodopa (IR CD-LD) in PD patients with motor fluctuations, using crossover data, and to evaluate which threshold values of improvement in finger-tapping and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores yield results most similar to those for trained raters' "on"/"off" assessments...

OBJECTIVES: Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine)...

BACKGROUND: Ever since the pioneering reports in the 60s, L-3,4-Dioxyphenylalanine (levodopa) has represented the gold standard for the treatment of Parkinson's Disease (PD). However, long-term levodopa (LD) treatment is frequently associated with fluctuations in motor response with serious impact on patient quality of life. The pharmacokinetic and pharmacodynamic properties of LD are pivotal to such motor fluctuations: discontinuous drug delivery, short half-life, poor bioavailability, and narrow therapeutic window are all crucial for such fluctuations...

Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor 'on-off' fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa...

BACKGROUND: IPX066 (Rytary®; carbidopa and levodopa [CD-LD] extended-release capsules) was designed to achieve therapeutic LD plasma concentrations within 1h of dosing and maintain LD concentrations for a prolonged duration in early or advanced Parkinson's disease (PD). METHODS: In this open-label study, patients underwent 6weeks of conversion to IPX066 from their prior controlled-release (CR)±immediate-release (IR) CD-LD therapy and 6months of maintenance (with an additional 6months of IPX066 at some sites)...

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...

Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease...

A new extended-release (ER) capsule formulation of carbidopa/levodopa (Rytary(®), Numient™, IPX066) is available for the treatment of Parkinson's disease (PD). Carbidopa/levodopa ER capsules contain beads of carbidopa and levodopa, designed to release the drugs at different rates in the gastrointestinal tract and provide constant therapeutic levodopa concentrations that are maintained for 4-5 h (after an initial peak at ≈ 1 h). In randomized phase III trials, oral carbidopa/levodopa ER was significantly more effective than placebo with regard to improving motor symptoms and activities of daily living in patients with early PD after 30 weeks' treatment, and provided significantly greater reductions in daily 'off-time' in patients with advanced PD than immediate-release (IR) carbidopa/levodopa or carbidopa/levodopa IR plus entacapone after a treatment period of 13 and 2 weeks, respectively, without increasing troublesome dyskinesia...

Parkinson disease is an age-related disorder of the central nervous system principally due to loss of dopamine-producing cells in the midbrain. Levodopa, in combination with carbidopa, is widely regarded as an effective treatment for the symptoms of Parkinson disease. A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model. Unified Parkinson Disease Rating Scale (UPDRS) part II plus part III scores from 171 North American patients treated with placebo or IPX066 for approximately 30 weeks from a double-blind, parallel-group, dose-ranging study were used to develop the pharmacodynamic model...

OBJECTIVES: IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. METHODS: Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23...

BACKGROUND: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. OBJECTIVE: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting...

Levodopa (l-dopa)-induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l-dopa-induced motor complications is still an important unmet need of PD therapy...

IPX066 (extended-release carbidopa-levodopa [ER CD-LD]) is an oral extended-release capsule formulation of carbidopa and levodopa. The single-dose pharmacokinetics of ER CD-LD (as 2 capsules; total dose, 97.5 mg-390 mg CD-LD) versus immediate-release (IR) CD-LD (25 mg-100 mg), sustained-release (CR) CD-LD (25 mg-100 mg), and CD-LD-entacapone (25 mg-100 mg-200 mg) was evaluated in healthy subjects. Following IR dosing, LD reached peak concentrations (Cmax ) at 1 hour; LD concentrations then decreased rapidly and were less than 10% of peak by 5 hours...

INTRODUCTION: Levodopa (LD) is the most effective treatment for Parkinson's disease (PD). However, chronic use of LD commonly results in the development of motor complications, including wearing off and dyskinesia. The presumption that the short serum half-life of LD is associated with the development of motor complications has raised the need to develop treatments with increased durations of stable LD concentrations. AREAS COVERED: We conducted a PubMed search for IPX066 articles and also reviewed abstracts from meetings that included this topic...

Ever 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 of l-dopa during long-term treatment. Discontinuous drug delivery resulting from the short half-life of l-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 of l-dopa are in different stages of clinical development and include novel formulations as well as nonoral routes of drug delivery...

BACKGROUND: IPX066, an investigational extended-release carbidopa-levodopa (CD-LD) preparation, has demonstrated a rapid attainment and prolonged maintenance of therapeutic LD plasma concentrations in advanced Parkinson's disease (PD). This phase-3 crossover study assessed its efficacy and safety vs. CD-LD plus entacapone (CL + E). METHODS: At baseline, all patients had motor fluctuations despite a stable regimen of CL + E or CD-LD-entacapone combination tablets (CLE)...

INTRODUCTION: L-DOPA has long been the 'gold standard' treatment for Parkinson's disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination. A longer acting preparation has long been sought. AREAS COVERED: We conducted PubMed search for IPX066 and reviewed abstracts from meetings that included the topic of PD. IPX066 is a novel mixed immediate release (IR) and sustained-release levodopa preparation designed to prolong the clinical effect of a single dose...

PURPOSE OF REVIEW: This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. RECENT FINDINGS: The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events...