Efficacy and Tolerability of Entacapone as Adjunctive Therapy to Levodopa in Patients with Parkinson’s Disease and End-of-Dose Deterioration in Daily Medical Practice: An Open, Multicenter StudyDurif F.a · Devaux I.a · Pere J.-J.b · Delumeau J.-C.c · Bourdeix I.b
aDepartment of Neurology, University Hospital of Clermont-Ferrand, bNovartis Pharma SA, Paris, France; cNovartis Pharma AG, Basel, Switzerland
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Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (≧3 daily doses) in patients with idiopathic Parkinson’s disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson’s Disease Rating Scale (UPDRS), (2) the reduction of ‘off’ time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator’s global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson’s Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (±7.04), which decreased to 8.5 (±6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in ‘off’ time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 ± 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.
© 2001 S. Karger AG, Basel
Marsden CD, Parkes JD: ‘On-off’ effects in patients with Parkinson’s disease on chronic levodopa therapy. Lancet 1976;i:292–296.
- Kaakkola S, Gordin A, Männistö P: General properties and clinical possibilities of new selective inhibitors of catechol-O-methyltransferase. Gen Pharmacol 1994;25:813–824.
Chase TN: Levodopa therapy: Consequences of the nonphysiologic replacement of dopamine. Neurology 1998;50(suppl 5):S17–S25.
Nutt JG, Carter JH, Lea ES, Woodward WR: Motor fluctuations during continuous levodopa infusions in patients with Parkinson’s disease. Mov Disord 1997;12:285–292.
- Ruottinen HM, Rinne UK: A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjunct to levodopa therapy in advanced Parkinson’s disease. Clin Neuropharmacol 1996;19:283–296.
- Keränen T, Gordin A, Karlsson M, Korpela K, Pentikäinen PJ, Rita H, Schultz E, Seppälä L, Wikberg T: Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone. Eur J Clin Pharmacol 1994;46:151–157.
- Nutt JG, Woodward WR, Beckner RM, Stone CK, Berggren K, Carter JH, Gancher ST, Hammerstad JP, Gordin A: Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 1994;44:913–919.
- Routtinen HM, Rinne UK: Entacapone prolongs levodopa response in a one-month double-blind study in parkinsonian patients with levodopa-related fluctuations. J Neurol Neurosurg Psychiatry 1996;60:36–40.
Stocchi F, De Pandis MF, Vacca L, Valente M, Brusa L, Ruggieri S: Entacapone efficacy in Parkinson’s disease. Mov Disord 2000;15(suppl 3):127.
Rinne UK, Larsen JP, Siden A, Worm-Peterson J: Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998;51:186–189.
- Parkinson Study Group: Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 1997;42:747–755.
Myllyla VV, Kultalahti E-R, Haapaniemi H, Leinonen M, the Filomen Study Group: Long-term safety of entacapone in patients with Parkinson’s disease. Eur J Neurol, in press.
Deuschl G, Poewe W, Poepping M, the Celomen Study Group: Efficacy and safety of entacapone as an adjunct to levodopa treatment in Parkinson’s disease (PD): Experience from the Austrian-German six months study. Parkinsonism-Related Disord 1999;5:75S.
Haasio K, Sopanen L, Nissinen E, Heinonen EH: Comparison of the preclinical safety of COMT inhibitors. Mov Disord 2000;15(suppl 3):111.
Nissinen E, Haasio K, Sopanen L, Heinonen EH: Effect of entacapone and tolcapone on mitochondrial function in vitro and in vivo. Mov Disord 2000;15(suppl 3):19.
Fahn S, Elton RL, Members of the UPDRS Development Committee: Unified Parkinson’s Disease Rating Scale; in Fahn S, Marsden CD, Calne DB, Goldstein M (eds): Recent Developments in Parkinson’s Disease. Florham Park, Macmillan Health Care Information, 1987, vol 2, pp 153–163.
Peto V, Jenkinson C, Fitzpatrick R: PDQ-39: A review of the development, validation and application of a Parkinson’s disease quality of life questionnaire and its associated measures. J Neurol 1998;245(suppl 1):S10–S14.
Luer MS: Interventions to achieve tonic exposure to levodopa: Delaying or preventing the onset of motor complications. Pharmacotherapy 1999;19(11):169S–179S.
Olanow CW, Obeso JA: Preventing levodopa-induced dyskinesia. Ann Neurol 2000;47:167–178.
Rinne UK, Kieburtz K, Gordin A: Effect of entacapone on quality of life related assessments in Parkinson’s disease. Mov Disord 2000;15(suppl 3):135.
Sagar H, Brooks D, UK-Irish Entacapone Study Group: The UK-Irish double-blind study of entacapone in Parkinson’s disease. Mov Disord 2000;15(suppl 3):135.
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