Top

Published in:

Open Access 01-12-2015 | Neurology and Preclinical Neurological Studies - Original Article

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Authors: Mikko Kuoppamäki, Mika Leinonen, Werner Poewe

Published in: Journal of Neural Transmission | Issue 12/2015

Abstract

Entacapone is frequently used together with levodopa/carbidopa (LC) and levodopa/benserazide (LB) in the treatment of Parkinson’s disease (PD) patients with wearing-off symptoms. It is generally assumed that the effects of entacapone are independent of the type of decarboxylase inhibitor used, but there is very little published data available on the efficacy of entacapone administered with LB versus LC. We have performed a pooled analysis of three randomized, double-blind, 6-month, phase III studies to compare the treatment effects of entacapone (compared to placebo) in PD patients receiving LC or LB. A total of 551 PD patients experiencing wearing-off were included in the analysis. 300 patients were on LB and 251 on LC at baseline. At 6 months, entacapone (compared to placebo) improved mean daily OFF-time in patients on LB and LC by 0.76 (p = 0.016) and 0.95 (p = 0.011) hours, respectively. The corresponding improvements in ON-time were 0.97 (p = 0.002) and 0.83 h (p = 0.022), respectively. The treatment effects of entacapone both in LB and LC users were statistically significant (p < 0.05) also in UPDRS II and III scores, except in UPDRS II scores in patients receiving LC (p = 0.20). None of the treatment effects of entacapone were statistically significantly different between patients receiving LB or LC. Reported adverse events were comparable between LB and LC users. We conclude that entacapone provided comparable benefits in PD patients with wearing-off symptoms using either LB or LC.

Baas H, Beiske AG, Ghika J, Jackson M, Oertel WH, Poewe W, Ransmayr G (1997) Catechol-O-methyltransferase with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry 63:421–428PubMedCentralCrossRefPubMed

Brooks DJ, Sagar H (2003) Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry 74:1071–1079PubMedCentralCrossRefPubMed

Dingemanse J, Jorga K, Zürcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P (1995) Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Br J Clin Pharmacol 40:253–262PubMedCentralCrossRefPubMed

Eggert K, Skogar O, Amar K, Luotonen L, Kuoppamäki M, Leinonen M, Nissinen H, Oertel W (2010) Direct switch from levodopa/benserazide or levodopa/carbidopa to levodopa/carbidopa/entacapone in Parkinson’s disease patients with wearing-off: efficacy, safety and feasibility–an open-label, 6-week study. J Neural Transm 117:333–342CrossRefPubMed

Greenacre JK, Coxon A, Petrie A, Reid JL (1976) Comparison of levodopa with carbidopa or benserazide in parkinsonism. Lancet 2:381–384CrossRefPubMed

Kaakkola S, Teräväinen H, Ahtila S, Rita H, Gordin A (1994) Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients. Neurology 44:77–80CrossRefPubMed

Kaakkola S, Teräväinen H, Ahtila S, Karlsson M, Naukkarinen T, Rita H, Gordin A (1995) Entacapone in combination with standard or controlled-release levodopa/carbidopa: a clinical and pharmacokinetic study in patients with Parkinson’s disease. Eur J Neurol 2:341–347CrossRefPubMed

Keränen T, Gordin A, Harjola VP, Karlsson M, Korpela K, Pentikäinen PJ, Rita H, Seppälä L, Wikberg T (1993) The effect of catechol-O-methyltransferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Clin Neuropharmacol 16:145–156CrossRefPubMed

Kuoppamäki M, Vahteristo M, Ellmén J, Kieburtz K (2014) Pooled analysis of phase III with entacapone in Parkinson’s disease. Acta Neurol Scand 130:239–247CrossRefPubMed

Nutt JG, Woodward WR, Beckner RM, Stone CK, Berggren K, Carter JH, Gancher ST, Hammerstad JP, Gordin A et al (1994) Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 44:913–919CrossRefPubMed

Pakkenberg H, Birket-Smith E, Dupont E, Hansen E, Mikkelsen B, Presthus J, Rautakorpi I, Riman E, Rinne UK (1976) Parkinson’s disease treated with Sinemet or Madopar. A controlled multicenter trial. Acta Neurol Scand 53:376–385CrossRefPubMed

Parkinson Study Group (1997) Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Parkinson Study Group. Ann Neurol 42:747–755CrossRef

Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M, Celomen Study Group (2002) 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). Acta Neurol Scand 105:245–255CrossRefPubMed

Rinne UK, Mölsä P (1979) Levodopa with benserazide or carbidopa in Parkinson’s disease. Neurology 29:1584–1589CrossRefPubMed

Rinne UK, Larsen JP, Siden A, Worm-Petersen J (1998) Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt study group. Neurology 51:1309–1314CrossRefPubMed

Sedêk G, Jorga K, Schmitt M, Burns RS, Leese P (1997) Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers. Clin Neuropharmacol 20:531–541CrossRefPubMed

Title: Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off
Authors: Mikko Kuoppamäki
Mika Leinonen
Werner Poewe
Publication date: 01-12-2015
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 12/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-015-1449-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2015

G2019S LRRK2 and aging confer susceptibility to proteasome inhibitor-induced neurotoxicity in nigrostriatal dopaminergic system

Quantitative assessment of non-motor fluctuations in Parkinson’s disease using the Non-Motor Symptoms Scale (NMSS)

Small intestine dysfunction in Parkinson’s disease

Vitamin D deficiency and its relationship with endothelial dysfunction in patients with early Parkinson’s disease

Erratum to: Is cognitive stability in Parkinson’s disease a predictable phenomenon? A 5-year follow-up study

Lymphocytes reduce nigrostriatal deficits in the 6-hydroxydopamine mouse model of Parkinson’s disease