Double-blind, Placebo-Controlled Study of Entacapone in Levodopa-Treated Patients With Stable Parkinson Disease

Olanow, C. Warren; Kieburtz, Karl; Stern, Matthew B.; Watts, R. L.; Langston, J. W.; Guarnieri, M.; Hubble, Jean

doi:10.1001/archneur.61.10.1563

Cited by 88 publications

(46 citation statements)

References 14 publications

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“…403,404 Similar results were reported with entacapone in one study, 405 whereas in another study, the addition of entacapone to levodopa in stable patients with PD did not improve UPDRS motor scores but did provide significant improvement in several quality-of-life measures, including the PD Questionnaire-39 and investigator and subject clinical global assessments. 406 Tolcapone is administered in doses of 100 or 200 mg TID, with the 200-mg dose providing greater efficacy. Entacapone is administered in a dose of 200 mg in combination with each dose of levodopa.…”

Section: Time (Months)mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

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747

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Section: Time (Months)mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

Self Cite

747

658

View full text Add to dashboard Cite

show abstract

“…Hence, the change in total UPDRS scores over time are more reasonably described using a linear model. Second, numerous literature reports suggest that disease progression follows a linear trend, beyond 12 weeks (after end of dose titration, if applicable) (9,10,(13)(14)(15)(16)(17)(18)(19). Trials which followed patients up to 5 years also support a linear disease progression.…”

Section: What Mathematical Model Can Reasonably Describe the Natural mentioning

confidence: 99%

Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson’s Disease

Bhattaram

Siddiqui

Kapcala

et al. 2009

AAPS J

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Abstract. Parkinson's disease is an age-related degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech, as well as other functions. Symptoms can include tremor, stiffness, slowness of movement, and impaired balance. An estimated four million people worldwide suffer from the disease, which usually affects people over the age of 60. Presently, there is no precedent for approving any drug as having a modifying effect (i.e., slowing or delaying) for disease progression of Parkinson's disease. Clinical trial designs such as delayed start and withdrawal are being proposed to discern symptomatic and protective effects. The current work focused on understanding the features of delayed start design using prior knowledge from published and data submitted to US Food and Drug Administration (US FDA) as part of drug approval or protocol evaluation. Clinical trial simulations were conducted to evaluate the false-positive rate, power under a new statistical analysis methodology, and various scenarios leading to patient discontinuations from clinical trials. The outcome of this work is part of the ongoing discussion between the US FDA and the pharmaceutical industry on the standards required for demonstrating disease-modifying effect using delayed start design.

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“…The administration of COMT inhibitors with LD ensures a more stable plasma LD level and, consequently, it improves motor fluctuations. The use of COMT inhibitors improve the half-life of LD, and the triple combination carbidopa (CD)-LD-entacapone provide the most sustained LD plasma level [22] . However, in longterm, this combination treatment is accompanied with the fluctuations of motor functions, dyskinesias and neuropsychiatric manifestations [23] .…”

Section: Current Therapeutic Approach Of Age-related Neurodegenerativmentioning

confidence: 99%

Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

Suksuphew

Noisa

2015

WJSC

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Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of agerelated neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients. Core tip: Neural stem cells present throughout life of human. The cells can be distinguished from differentiated progeny by acknowledging a few key features, including proliferation, self-renewal, multipotency and molecular markers. These features make neural stem cells as an essential component in the development of nervous system and in maintaining cell number of adult nervous tissues following injury and diseases. Besides conventional treatments, neural stem cells have been proposed as a promising approach to cure patients with neurodegenerative diseases. Several animal studies showed the efficiency of neural stem cells in treating age-related neurodegenerative diseases, in particular

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Double-blind, Placebo-Controlled Study of Entacapone in Levodopa-Treated Patients With Stable Parkinson Disease

Abstract: The catechol O-methyltransferase inhibitor entacapone, used as an adjunct to levodopa in PD patients who do not experience motor fluctuations, does not improve Unified Parkinson's Disease Rating Scale motor scores but does improve a variety of quality-of-life measures.

Cited by 88 publications

References 14 publications

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson’s Disease

Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

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