Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal Levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study)

Poewe, Werner; Deuschl, Günther; Gordin, A.; Kultalahti, E.-R.; Leinonen, Mika

doi:10.1034/j.1600-0404.2002.1o174.x

Cited by 194 publications

(165 citation statements)

References 23 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…The funnel plot corresponding to the total incidences of treatment-emergent AEs identifies the trial by Poewe et al 14 as an outlier among the trials with respect to the total AE incidences (see Figure 3A). No heterogeneities were detected within both groups of studies however.…”

Section: Safety Endpointsmentioning

confidence: 99%

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

Schnitker¹,

Müller²

2015

European Neurological Review

View full text Add to dashboard Cite

Chronic levodopa (L-dopa) treatment of Parkinson's disease (PD) patients is sooner or later associated with the onset of motor complications, for example wearing off and dyskinesia. PD patients with motor complications usually require the addition of further PD drugs to reduce these L-dopa side effects and enhance its efficacy. Entacapone is an available catechol-O-methyltransferase (COMT) inhibitor, which was extensively investigated as add-on to L-dopa/dopadecarboxylase inhibitor (DDCI) application in PD patients. Safinamide, a watersoluble, orally active a-aminoamide derivative, which modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action, has been studied in two placebo-controlled clinical trials as add-on therapy to L-dopa in fluctuating PD patients.To date, there are no head-to-head clinical trials comparing the efficacy of safinamide and entacapone in the clinic. The aim of this meta-analysis was to determine effect sizes of safinamide and entacapone as add-on treatment to L-dopa in fluctuating PD patients.A systematic search of the literature on entacapone trials up to the end of September 2014 was first conducted on the MEDLINE and EMBASE databases in order to identify appropriate studies. Definition criteria for inclusion were prospective, randomised, placebocontrolled and double-blinded trials on the efficacy and safety of entacapone or safinamide in fluctuating L-dopa-treated PD patients.Four studies for entacapone and two trials on safinamide were considered. Data from the safinamide trials were provided by Zambon and therefore 'safinamide' was not used as a search term. Safinamide and entacapone treatment was comparable in terms of the main efficacy variables (off time, percentage on time, Unified Parkinson's Disease Rating Scale). Significant advantages in favour of safinamide were shown in terms of the total incidence of adverse events (AEs) in comparison to placebo, the study discontinuation due to AEs and deaths and in the risk differences of the AEs versus placebo, particularly for nausea, vomiting, diarrhoea, dizziness, urine abnormality and shortness of breath. The odds ratio (OR) of 0.907 for any AE corresponds to an overall AE rate of 68.7 % for safinamide whereas the OR of 2.089 to an overall AE rate of 84.4 % for entacapone. KeywordsAdd-on therapy, entacapone, levodopa, L-dopa, Parkinson's disease, safinamide Disclosure: Jörg Schnitker has received funding from Zambon SpA to perform the statistical meta-analysis and to write the report. Thomas Müller participated in advisory boards for the safinamide studies and served as a principal investigator.

show abstract

Section: Safety Endpointsmentioning

confidence: 99%

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

Schnitker¹,

Müller²

2015

European Neurological Review

View full text Add to dashboard Cite

show abstract

“…22 Only 78% of patients randomized completed the trial. Off time decreased by 25.8% (1.6 hours) with entacapone compared to 13.4% (0.9 hours) with placebo.…”

Section: R E T I R E D R E T I R E Dmentioning

confidence: 99%

Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): [RETIRED]

Pahwa¹,

Factor²,

Lyons³

et al. 2006

Neurology

464

314

View full text Add to dashboard Cite

show abstract

“…Inhibition of COMT by entacapone prolongs the half-life of levodopa (Nutt et al 1994;Ruottinen and Rinne 1996) and this is associated with improved clinical efficacy in PD patients (Kaakkola and Wurtman 1993;Nutt et al 1994;Ruottinen and Rinne 1996;Parkinson Study Group 1997;Rinne 1998;Poewe 2002Grandas et al 2007;Deuschl et al 2007;Müller et al 2007) and in experimental models of parkinsonism (Smith et al 2003;Marin et al 2005Marin et al , 2006. By extending the half-life of levodopa with entacapone, it is possible to deliver the drug in a way that is less pulsatile, thereby allowing the benefit of levodopa with a reduced risk for motor complications.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes

Marı́n¹,

Aguilar²,

Mengod³

et al. 2008

Neurobiology of Disease

View full text Add to dashboard Cite

Coadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long duration response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic mechanisms and molecular changes in hemiparkinsonian rats. 6-hydroxydopamine-unilaterally lesion rats were treated with levodopa (25 mg /kg)+vehicle; levodopa+entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and the apomorphine-induced rotations were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin and dopamine D-3 receptors mRNAs, subthalamic cytochrome oxidase mRNA and nigral glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did no modify neither the apomorphine-induced rotational behavior nor the molecular changes. Our results suggest that the effects of entacapone on levodopa-induced motor response are no mediated by postsynaptic mechanisms and that administration of entacapone is not able to normalize the molecular alterations induced by levodopa in the basal ganglia.

show abstract

Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal Levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study)

Abstract: Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.

Cited by 194 publications

References 23 publications

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): [RETIRED]

Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes

Contact Info

Product

Resources

About