TY - JOUR
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
Y1 - 1997
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.
KW - 5-year study
KW - Activities of daily living
KW - Nottingham Health Profile
KW - Parkinson’s disease
KW - Sinemet
KW - Sinemet CR
KW - UPDRS
UR - http://www.scopus.com/inward/record.url?scp=8044229410&partnerID=8YFLogxK
U2 - 10.1159/000117399
DO - 10.1159/000117399
M3 - Article
C2 - 9018028
AN - SCOPUS:8044229410
SN - 0014-3022
VL - 37
SP - 23
EP - 27
JO - European Neurology
JF - European Neurology
IS - 1
ER -