Journal of Neural Transmission

, Volume 117, Issue 3, pp 333–342 | Cite as

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

  • Karla Eggert
  • Örjan Skogar
  • Khaled Amar
  • Liisa Luotonen
  • Mikko Kuoppamäki
  • Mika Leinonen
  • Helena Nissinen
  • Wolfgang Oertel
Movement Disorders - Original Article

Abstract

The study objective was to assess the efficacy, safety and feasibility of switching from levodopa/benserazide (LB) or levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in Parkinson’s disease (PD) patients with wearing-off. This was a multicenter, open-label, 6-week study; the primary outcome was success rate based on the patient-assessed Clinical Global Impression of Change (P-CGI-C). Secondary outcomes included investigator-assessed CGI-C (I-CGI-C), change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS), motor/non-motor wearing-off symptoms and quality of life–visual analog scale (QoL-VAS). After switching to LCE, 77% of patients reported an ‘improvement’ (p < 0.0001 vs. patients reporting ‘no change or worsening’). Significant improvements were seen in I-CGI-C, UPDRS and QoL-VAS, regardless of prior therapy. Oral levodopa dosing was increased in 28% of patients; the primary outcome remained significant when these patients were excluded. The data suggest that switching from LB/LC to LCE provided a significant benefit in PD patients with wearing-off.

Keywords

Levodopa Entacapone Carbidopa Benserazide Wearing-off 9-item Wearing-off Questionnaire 

References

  1. 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 74:1071–1079CrossRefPubMedGoogle Scholar
  2. Brooks DJ, Agid Y, Eggert K, Widner H, Ostergaard K, Holopainen A, The TC-INIT Study Group (2005) Treatment of end-of-dose wearing-off in Parkinson’s disease: Stalevo® (Levodopa/Carbidopa/Entacapone) and levodopa/DDCI given in combination with Comtess®/Comtan® (Entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment. Eur Neurol 53:197–202CrossRefPubMedGoogle Scholar
  3. de la Fuente-Fernandez R, Stoessl AJ (2004) The biochemical bases of the placebo effect. Sci Eng Ethics 10:143–150CrossRefPubMedGoogle Scholar
  4. de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2004) Placebo mechanisms and reward circuitry: clues from Parkinson’s disease. Biol Psychiatry 56:67–71CrossRefPubMedGoogle Scholar
  5. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170CrossRefPubMedGoogle Scholar
  6. Gordin A, Kaakkola S, Teravainen H (2004) Clinical advantages of COMT inhibition with entacapone––a review. J Neural Transm 111:1343–1363CrossRefPubMedGoogle Scholar
  7. Koller W, Guarnieri M, Hubble J, Rabinowicz AL, Silver D (2005) An open-label evaluation of the tolerability and safety of Stalevo® (carbidopa, levodopa and entacapone) in Parkinson’s disease patients experiencing wearing-off. J Neural Transm 112:221–230CrossRefPubMedGoogle Scholar
  8. Kuoppamäki M, Korpela K, Marttila R, Kaasinen V, Hartikainen P, Lyytinen J, Kaakkola S, Hänninen J, Löyttyniemi E, Kailajärvi M, Ruokoniemi P, Ellmén J (2009) Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/carbidopa when administered four- or five-times daily. Eur J Clin Pharmacol 65:443–455CrossRefPubMedGoogle Scholar
  9. Linazasoro G, Kulisevsky J, Hernandez B (2008) Should levodopa dose be reduced when switched to stalevo? Eur J Neurol 15:257–261CrossRefPubMedGoogle Scholar
  10. Muller T, Erdmann C, Muhlack S, Bremen D, Przuntek H, Goetze O, Woitalla D (2006a) Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson’s disease. J Neural Transm 113:1441–1448CrossRefPubMedGoogle Scholar
  11. Muller T, Erdmann C, Muhlack S, Bremen D, Przuntek H, Woitalla D (2006b) Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels. Mov Disord 21:332–336CrossRefPubMedGoogle Scholar
  12. Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonuccelli U, Damier P, De Yebenes J, Gershanik O, Guttman M, Grandas F, Hallett M, Hornykiewicz O, Jenner P, Katzenschlager R, Langston WJ, LeWitt P, Melamed E, Mena MA, Michel PP, Mytilineou C, Obeso JA, Poewe W, Quinn N, Raisman-Vozari R, Rajput AH, Rascol O, Sampaio C, Stocchi F (2004) Levodopa in the treatment of Parkinson’s disease: current controversies. Mov Disord 19:997–1005CrossRefPubMedGoogle Scholar
  13. Parkinson Study Group (1997) Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 42:747–755CrossRefGoogle Scholar
  14. Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M (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 Neurologica Scand 105:245–255CrossRefGoogle Scholar
  15. Rinne UK, Larsen JP, Siden A, Worm-Petersen J, The Nomecomt Study Group (1998) Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 51:1309–1314PubMedGoogle Scholar
  16. Stacy M, Hauser R, Oertel W, Schapira A, Sethi K, Stocchi F, Tolosa E (2006) End-of-dose wearing off in Parkinson disease: a 9-question survey assessment. Clin Neuropharmacol 29:312–321CrossRefPubMedGoogle Scholar
  17. Stocchi F (2006) The levodopa wearing-off phenomenon in Parkinson’s disease: pharmacokinetic considerations. Expert Opin Pharmacother 7:1399–1407CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Karla Eggert
    • 1
  • Örjan Skogar
    • 2
  • Khaled Amar
    • 3
  • Liisa Luotonen
    • 4
  • Mikko Kuoppamäki
    • 4
    • 5
  • Mika Leinonen
    • 6
  • Helena Nissinen
    • 7
  • Wolfgang Oertel
    • 1
  1. 1.Department of NeurologyPhilipps-University MarburgMarburgGermany
  2. 2.Länssjukhuset RyhovJönköpingSweden
  3. 3.Royal Bournemouth HospitalBournemouthUK
  4. 4.Orion PharmaTurkuFinland
  5. 5.Department of NeurologyUniversity of TurkuTurkuFinland
  6. 6.4PharmaKistaSweden
  7. 7.Orion PharmaEspooFinland

Personalised recommendations