Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa

Charles H. Adler, Carlos Singer, Christopher O'Brien, Robert A. Hauser, Mark F. Lew, Kenneth L. Marek, Ernest Dorflinger, Simon Pedder, Dennis Deptula, Kisook Yoo

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Objective: To assess the efficacy and tolerability of the catechol-O- methyltransferase inhibitor tolcapone in reducing 'off/on' fluctuations in levodopa-treated parkinsonian patients. Design: A randomized, double-blind, placebo-controlled, parallel-group study. Setting: Fifteen Parkinson disease clinics. Patients: Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. Interventions: In addition to their usual levodopa- carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. Primary Outcome Measure: Change in daily off/on time. Results: Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively (P<.001 vs placebo). Investigators' global measures of disease severity indicated that significantly more tolcapone-treated patients had reduced wearing off and symptom severity (P<.001 vs placebo). No significant change in quality-of-life measures occurred. Clinical improvements occurred despite a reduction in total daily levodopa dose of 185.5 mg (23%) in the tolcapone, 100 mg 3 times daily, group and 251.5 mg (29%) in the 200 mg 3 times daily group. Principal adverse events (mainly dyskinesia and nausea) were levodopa related, were not treatment limiting, and were seldom reported as reasons for withdrawal. The frequency of withdrawals because of adverse events was similar in all groups (3% to 7%). Conclusions: Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.

Original languageEnglish
Pages (from-to)1089-1095
Number of pages7
JournalArchives of Neurology
Volume55
Issue number8
DOIs
StatePublished - Aug 1 1998

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Parkinson Disease
Placebos
Levodopa
Dyskinesias
Nausea
levodopa drug combination carbidopa
tolcapone
Controlled
Placebo
Parkinson's Disease
Outpatients
Quality of Life
Research Personnel
Outcome Assessment (Health Care)
Dose
Fluctuations

ASJC Scopus subject areas

  • Neuroscience(all)

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Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. / Adler, Charles H.; Singer, Carlos; O'Brien, Christopher; Hauser, Robert A.; Lew, Mark F.; Marek, Kenneth L.; Dorflinger, Ernest; Pedder, Simon; Deptula, Dennis; Yoo, Kisook.

In: Archives of Neurology, Vol. 55, No. 8, 01.08.1998, p. 1089-1095.

Research output: Contribution to journalArticle

Adler, CH, Singer, C, O'Brien, C, Hauser, RA, Lew, MF, Marek, KL, Dorflinger, E, Pedder, S, Deptula, D & Yoo, K 1998, 'Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa', Archives of Neurology, vol. 55, no. 8, pp. 1089-1095. https://doi.org/10.1001/archneur.55.8.1089
Adler, Charles H. ; Singer, Carlos ; O'Brien, Christopher ; Hauser, Robert A. ; Lew, Mark F. ; Marek, Kenneth L. ; Dorflinger, Ernest ; Pedder, Simon ; Deptula, Dennis ; Yoo, Kisook. / Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. In: Archives of Neurology. 1998 ; Vol. 55, No. 8. pp. 1089-1095.
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abstract = "Objective: To assess the efficacy and tolerability of the catechol-O- methyltransferase inhibitor tolcapone in reducing 'off/on' fluctuations in levodopa-treated parkinsonian patients. Design: A randomized, double-blind, placebo-controlled, parallel-group study. Setting: Fifteen Parkinson disease clinics. Patients: Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. Interventions: In addition to their usual levodopa- carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. Primary Outcome Measure: Change in daily off/on time. Results: Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively (P<.001 vs placebo). Investigators' global measures of disease severity indicated that significantly more tolcapone-treated patients had reduced wearing off and symptom severity (P<.001 vs placebo). No significant change in quality-of-life measures occurred. Clinical improvements occurred despite a reduction in total daily levodopa dose of 185.5 mg (23{\%}) in the tolcapone, 100 mg 3 times daily, group and 251.5 mg (29{\%}) in the 200 mg 3 times daily group. Principal adverse events (mainly dyskinesia and nausea) were levodopa related, were not treatment limiting, and were seldom reported as reasons for withdrawal. The frequency of withdrawals because of adverse events was similar in all groups (3{\%} to 7{\%}). Conclusions: Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.",
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AU - Adler, Charles H.

AU - Singer, Carlos

AU - O'Brien, Christopher

AU - Hauser, Robert A.

AU - Lew, Mark F.

AU - Marek, Kenneth L.

AU - Dorflinger, Ernest

AU - Pedder, Simon

AU - Deptula, Dennis

AU - Yoo, Kisook

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N2 - Objective: To assess the efficacy and tolerability of the catechol-O- methyltransferase inhibitor tolcapone in reducing 'off/on' fluctuations in levodopa-treated parkinsonian patients. Design: A randomized, double-blind, placebo-controlled, parallel-group study. Setting: Fifteen Parkinson disease clinics. Patients: Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. Interventions: In addition to their usual levodopa- carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. Primary Outcome Measure: Change in daily off/on time. Results: Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively (P<.001 vs placebo). Investigators' global measures of disease severity indicated that significantly more tolcapone-treated patients had reduced wearing off and symptom severity (P<.001 vs placebo). No significant change in quality-of-life measures occurred. Clinical improvements occurred despite a reduction in total daily levodopa dose of 185.5 mg (23%) in the tolcapone, 100 mg 3 times daily, group and 251.5 mg (29%) in the 200 mg 3 times daily group. Principal adverse events (mainly dyskinesia and nausea) were levodopa related, were not treatment limiting, and were seldom reported as reasons for withdrawal. The frequency of withdrawals because of adverse events was similar in all groups (3% to 7%). Conclusions: Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.

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