Comparison of immediate-release and controlled release carbidopa/levodopa in parkinson’s disease

The CR First Study Group

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Background: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson’s disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome. We conducted a large, 5-year, multicenter study to address this hypothesis. Methods: Six hundred and eighteen nonfluctuating patients with Parkinson’s disease never exposed to levodopa therapy were randomized to (Sinemet® CR 50/200) sustained-release or immediate-release (Sinemet® 25/100) carbidopa/levodopa preparations in 35 centers worldwide. Dosage titration occurred over the 5 years of evaluations to maintain an optimal response. The primary endpoint, the ‘event’, was the presence of motor fluctuations, as defined by 20% ‘off time or 10% ‘on’ time with dyskinesias as recorded in the patient diary, or greater than or equal to a 50% positive response on the physician fluctuations questionnaire. Clinical rating scales, Nottingham Health Profile (NHP) and adverse reactions were also recorded. Findings: During the 5 years of the study, both treatment groups responded extremely well to therapy. The incidence of all patients reaching the ‘event’ was low, approximately 20% by diary criteria and 16% by questionnaire definition, and there was no significant difference between the two treatment groups. Activities of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS) consistently favored the Sinemet CR treatment group and a number of the NHP scales also favored the CR group. Based upon the frequency of adverse experiences, and the overall low incidence of withdrawals, the two treatment groups demonstrated very similar safety profiles. The most common drug-related effect was nausea; seen in 20% of patients. Other drug-related effects were dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug-related withdrawals were less than 10% of all patients, primarily due to nervous/psychiatric complaints. Interpretation: During a 5-year treatment period, control of parkinsonian symptoms was maintained by both immediate-release and sustained-release carbidopa/levodopa. Both treatment regimens were associated with a low incidence of motor fluctuations and dyskinesias. There was a statistically significant difference (p < 0.05) in activities of daily living as measured by the UPDRS in favor of Sinemet CR.

Original languageEnglish (US)
Pages (from-to)23-27
Number of pages5
JournalEuropean Neurology
Volume37
Issue number1
DOIs
StatePublished - Jan 1 1997

Fingerprint

Parkinson Disease
Dyskinesias
Levodopa
Therapeutics
Activities of Daily Living
Incidence
levodopa drug combination carbidopa
Pharmaceutical Preparations
Delayed-Action Preparations
Health
Sleep Initiation and Maintenance Disorders
Dizziness
Nausea
Abdominal Pain
Multicenter Studies
Headache
Psychiatry
Depression
Physicians
Safety

Keywords

  • 5-year study
  • Activities of daily living
  • Nottingham Health Profile
  • Parkinson’s disease
  • Sinemet
  • Sinemet CR
  • UPDRS

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Comparison of immediate-release and controlled release carbidopa/levodopa in parkinson’s disease. / The CR First Study Group.

In: European Neurology, Vol. 37, No. 1, 01.01.1997, p. 23-27.

Research output: Contribution to journalArticle

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abstract = "Background: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson’s disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome. We conducted a large, 5-year, multicenter study to address this hypothesis. Methods: Six hundred and eighteen nonfluctuating patients with Parkinson’s disease never exposed to levodopa therapy were randomized to (Sinemet{\circledR} CR 50/200) sustained-release or immediate-release (Sinemet{\circledR} 25/100) carbidopa/levodopa preparations in 35 centers worldwide. Dosage titration occurred over the 5 years of evaluations to maintain an optimal response. The primary endpoint, the ‘event’, was the presence of motor fluctuations, as defined by 20{\%} ‘off time or 10{\%} ‘on’ time with dyskinesias as recorded in the patient diary, or greater than or equal to a 50{\%} positive response on the physician fluctuations questionnaire. Clinical rating scales, Nottingham Health Profile (NHP) and adverse reactions were also recorded. Findings: During the 5 years of the study, both treatment groups responded extremely well to therapy. The incidence of all patients reaching the ‘event’ was low, approximately 20{\%} by diary criteria and 16{\%} by questionnaire definition, and there was no significant difference between the two treatment groups. Activities of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS) consistently favored the Sinemet CR treatment group and a number of the NHP scales also favored the CR group. Based upon the frequency of adverse experiences, and the overall low incidence of withdrawals, the two treatment groups demonstrated very similar safety profiles. The most common drug-related effect was nausea; seen in 20{\%} of patients. Other drug-related effects were dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug-related withdrawals were less than 10{\%} of all patients, primarily due to nervous/psychiatric complaints. Interpretation: During a 5-year treatment period, control of parkinsonian symptoms was maintained by both immediate-release and sustained-release carbidopa/levodopa. Both treatment regimens were associated with a low incidence of motor fluctuations and dyskinesias. There was a statistically significant difference (p < 0.05) in activities of daily living as measured by the UPDRS in favor of Sinemet CR.",
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author = "{The CR First Study Group} and Gilbert Block and Charles Liss and Scott Reines and Joseph Irr and Donald Nibbelink and Johan Aarli and M. Aguilar and Suzanne Ahrens and A. Bakheit and Barry Baumel and John Bertoni and Rudy Capildeo and Alexandre Castro-Caldas and Luis Deza and Ivan Donaldson and Georges Franck and Jose Fusillo and Serge Gauthier and Oscar Gershanik and Granerus, {Ann Katherine} and Hauser, {Robert A.} and Keven Hennessey and Hutton, {J. Thomas} and Ronald Joffe and William Koller and Barbara Last and Peter LeWitt and Bruno Mamoli and Bala Manyam and Margery Mark and Kenneth Nakano and Paul Nausieda and Enrique Otero and George Paulson and Michaela Pinter and Stephen Reich and Robert Rodnitzky and Jacob Sage and Cristina Sampaio and Betty Smith and Heikki Ter{\"a}v{\"a}inen and James Tetrud and Eduardo Tolosa and Gudrun Ulm and Francisco Valesco",
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T1 - Comparison of immediate-release and controlled release carbidopa/levodopa in parkinson’s disease

AU - The CR First Study Group

AU - Block, Gilbert

AU - Liss, Charles

AU - Reines, Scott

AU - Irr, Joseph

AU - Nibbelink, Donald

AU - Aarli, Johan

AU - Aguilar, M.

AU - Ahrens, Suzanne

AU - Bakheit, A.

AU - Baumel, Barry

AU - Bertoni, John

AU - Capildeo, Rudy

AU - Castro-Caldas, Alexandre

AU - Deza, Luis

AU - Donaldson, Ivan

AU - Franck, Georges

AU - Fusillo, Jose

AU - Gauthier, Serge

AU - Gershanik, Oscar

AU - Granerus, Ann Katherine

AU - Hauser, Robert A.

AU - Hennessey, Keven

AU - Hutton, J. Thomas

AU - Joffe, Ronald

AU - Koller, William

AU - Last, Barbara

AU - LeWitt, Peter

AU - Mamoli, Bruno

AU - Manyam, Bala

AU - Mark, Margery

AU - Nakano, Kenneth

AU - Nausieda, Paul

AU - Otero, Enrique

AU - Paulson, George

AU - Pinter, Michaela

AU - Reich, Stephen

AU - Rodnitzky, Robert

AU - Sage, Jacob

AU - Sampaio, Cristina

AU - Smith, Betty

AU - Teräväinen, Heikki

AU - Tetrud, James

AU - Tolosa, Eduardo

AU - Ulm, Gudrun

AU - Valesco, Francisco

PY - 1997/1/1

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N2 - Background: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson’s disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome. We conducted a large, 5-year, multicenter study to address this hypothesis. Methods: Six hundred and eighteen nonfluctuating patients with Parkinson’s disease never exposed to levodopa therapy were randomized to (Sinemet® CR 50/200) sustained-release or immediate-release (Sinemet® 25/100) carbidopa/levodopa preparations in 35 centers worldwide. Dosage titration occurred over the 5 years of evaluations to maintain an optimal response. The primary endpoint, the ‘event’, was the presence of motor fluctuations, as defined by 20% ‘off time or 10% ‘on’ time with dyskinesias as recorded in the patient diary, or greater than or equal to a 50% positive response on the physician fluctuations questionnaire. Clinical rating scales, Nottingham Health Profile (NHP) and adverse reactions were also recorded. Findings: During the 5 years of the study, both treatment groups responded extremely well to therapy. The incidence of all patients reaching the ‘event’ was low, approximately 20% by diary criteria and 16% by questionnaire definition, and there was no significant difference between the two treatment groups. Activities of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS) consistently favored the Sinemet CR treatment group and a number of the NHP scales also favored the CR group. Based upon the frequency of adverse experiences, and the overall low incidence of withdrawals, the two treatment groups demonstrated very similar safety profiles. The most common drug-related effect was nausea; seen in 20% of patients. Other drug-related effects were dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug-related withdrawals were less than 10% of all patients, primarily due to nervous/psychiatric complaints. Interpretation: During a 5-year treatment period, control of parkinsonian symptoms was maintained by both immediate-release and sustained-release carbidopa/levodopa. Both treatment regimens were associated with a low incidence of motor fluctuations and dyskinesias. There was a statistically significant difference (p < 0.05) in activities of daily living as measured by the UPDRS in favor of Sinemet CR.

AB - Background: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson’s disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome. We conducted a large, 5-year, multicenter study to address this hypothesis. Methods: Six hundred and eighteen nonfluctuating patients with Parkinson’s disease never exposed to levodopa therapy were randomized to (Sinemet® CR 50/200) sustained-release or immediate-release (Sinemet® 25/100) carbidopa/levodopa preparations in 35 centers worldwide. Dosage titration occurred over the 5 years of evaluations to maintain an optimal response. The primary endpoint, the ‘event’, was the presence of motor fluctuations, as defined by 20% ‘off time or 10% ‘on’ time with dyskinesias as recorded in the patient diary, or greater than or equal to a 50% positive response on the physician fluctuations questionnaire. Clinical rating scales, Nottingham Health Profile (NHP) and adverse reactions were also recorded. Findings: During the 5 years of the study, both treatment groups responded extremely well to therapy. The incidence of all patients reaching the ‘event’ was low, approximately 20% by diary criteria and 16% by questionnaire definition, and there was no significant difference between the two treatment groups. Activities of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS) consistently favored the Sinemet CR treatment group and a number of the NHP scales also favored the CR group. Based upon the frequency of adverse experiences, and the overall low incidence of withdrawals, the two treatment groups demonstrated very similar safety profiles. The most common drug-related effect was nausea; seen in 20% of patients. Other drug-related effects were dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug-related withdrawals were less than 10% of all patients, primarily due to nervous/psychiatric complaints. Interpretation: During a 5-year treatment period, control of parkinsonian symptoms was maintained by both immediate-release and sustained-release carbidopa/levodopa. Both treatment regimens were associated with a low incidence of motor fluctuations and dyskinesias. There was a statistically significant difference (p < 0.05) in activities of daily living as measured by the UPDRS in favor of Sinemet CR.

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