Movement Disorders (revue)

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Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations

Identifieur interne : 000386 ( PascalFrancis/Curation ); précédent : 000385; suivant : 000387

Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations

Auteurs : William Koller [États-Unis] ; Andrew Lees [Royaume-Uni] ; Miroslava Doder [Royaume-Uni] ; Mariese Hely [Australie]

Source :

RBID : Pascal:02-0049768

Descripteurs français

English descriptors

Abstract

In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of life, was better tolerated, and had a more favorable adverse-event profile than pergolide.
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A08 01  1  ENG  @1 Randomized trial of tolcapone versus pergolide as add-on to levodopa therapy in Parkinson's disease patients with motor fluctuations
A11 01  1    @1 KOLLER (William)
A11 02  1    @1 LEES (Andrew)
A11 03  1    @1 DODER (Miroslava)
A11 04  1    @1 HELY (Mariese)
A14 01      @1 University of Miami @2 Miami, Florida @3 USA @Z 1 aut.
A14 02      @1 National Hospital for Neurology and Neurosurgery @2 London @3 GBR @Z 2 aut. @Z 3 aut.
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C01 01    ENG  @0 In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of life, was better tolerated, and had a more favorable adverse-event profile than pergolide.
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N21       @1 021

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Pascal:02-0049768

Le document en format XML

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<div type="abstract" xml:lang="en">In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of life, was better tolerated, and had a more favorable adverse-event profile than pergolide.</div>
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<s0>In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of life, was better tolerated, and had a more favorable adverse-event profile than pergolide.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002B02B05</s0>
</fC02>
<fC02 i1="02" i2="X">
<s0>235</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Parkinson maladie</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Parkinson disease</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Parkinson enfermedad</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Lévodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Chimiothérapie</s0>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Chemotherapy</s0>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Quimioterapia</s0>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Antiparkinsonien</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Antiparkinson agent</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Antiparkinsoniano</s0>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Tolcapone</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Tolcapone</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Tolcapona</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Inhibiteur enzyme</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Enzyme inhibitor</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Inhibidor enzima</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Catechol O-methyltransferase</s0>
<s2>FE</s2>
<s5>09</s5>
<s6>Catechol «O»-methyltransferase</s6>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Catechol O-methyltransferase</s0>
<s2>FE</s2>
<s5>09</s5>
<s6>Catechol «O»-methyltransferase</s6>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Catechol O-methyltransferase</s0>
<s2>FE</s2>
<s5>09</s5>
<s6>Catechol «O»-methyltransferase</s6>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Pergolide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Pergolide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Pergolida</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Agoniste</s0>
<s5>11</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Agonist</s0>
<s5>11</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Agonista</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE">
<s0>Récepteur dopaminergique</s0>
<s5>12</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG">
<s0>Dopamine receptor</s0>
<s5>12</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA">
<s0>Receptor dopaminérgico</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE">
<s0>Stimulant dopaminergique</s0>
<s5>13</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG">
<s0>Dopamine agonist</s0>
<s5>13</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA">
<s0>Estimulante dopaminérgico</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE">
<s0>Randomisation</s0>
<s5>16</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG">
<s0>Randomization</s0>
<s5>16</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA">
<s0>Aleatorización</s0>
<s5>16</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE">
<s0>Etude comparative</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG">
<s0>Comparative study</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA">
<s0>Estudio comparativo</s0>
<s5>17</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE">
<s0>Traitement</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG">
<s0>Treatment</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA">
<s0>Tratamiento</s0>
<s5>18</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE">
<s0>Association médicamenteuse</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG">
<s0>Drug combination</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA">
<s0>Asociación medicamentosa</s0>
<s5>19</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE">
<s0>Adulte</s0>
<s5>20</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG">
<s0>Adult</s0>
<s5>20</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA">
<s0>Adulto</s0>
<s5>20</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE">
<s0>Toxicité</s0>
<s5>23</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG">
<s0>Toxicity</s0>
<s5>23</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA">
<s0>Toxicidad</s0>
<s5>23</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE">
<s0>Ergot dérivé</s0>
<s5>31</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG">
<s0>Ergot derivatives</s0>
<s5>31</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA">
<s0>Ergot derivado</s0>
<s5>31</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE">
<s0>Fluctuation motrice</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Methyltransferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Methyltransferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Methyltransferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Transferases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Enzyme</s0>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Enzyme</s0>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Enzima</s0>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Homme</s0>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Human</s0>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Hombre</s0>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Système nerveux pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Nervous system diseases</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Sistema nervioso patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Système nerveux central pathologie</s0>
<s5>38</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Central nervous system disease</s0>
<s5>38</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Sistema nervosio central patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Encéphale pathologie</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Cerebral disorder</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Encéfalo patología</s0>
<s5>39</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Extrapyramidal syndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Extrapiramidal síndrome</s0>
<s5>40</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE">
<s0>Maladie dégénérative</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG">
<s0>Degenerative disease</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA">
<s0>Enfermedad degenerativa</s0>
<s5>41</s5>
</fC07>
<fN21>
<s1>021</s1>
</fN21>
</pA>
</standard>
</inist>
</record>

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