Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease
Identifieur interne : 000A86 ( PascalFrancis/Checkpoint ); précédent : 000A85; suivant : 000A87Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease
Auteurs : Olivier Rascol [France] ; Paolo Barone [Italie] ; Robert A. Hauser [États-Unis] ; Yoshikuni Mizuno [Japon] ; Werner Poewe [Autriche] ; Anthony H. V. Schapira [Royaume-Uni] ; Laurence Salin [France] ; Mandy Sohr [Allemagne] ; Catherine Debieuvre [France]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.SI%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.
Affiliations:
- Allemagne, Autriche, France, Italie, Japon, Royaume-Uni, États-Unis
- Angleterre, Floride, Grand Londres, Midi-Pyrénées, Tyrol (Land)
- Innsbruck, Londres, Reims, Tampa, Tokyo, Toulouse
- Université Toulouse III - Paul Sabatier, Université de Floride du Sud, Université de Toulouse, Université de médecine d'Innsbruck
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, INSERM CIC9302-UMR825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Midi-Pyrénées</region></placeName><orgName type="university" n="3">Université Toulouse III - Paul Sabatier</orgName><orgName type="institution" wicri:auto="newGroup">Université de Toulouse</orgName></affiliation></author><author><name sortKey="Barone, Paolo" sort="Barone, Paolo" uniqKey="Barone P" first="Paolo" last="Barone">Paolo Barone</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurological Sciences, University of Naples</s1><s2>Naples</s2><s3>ITA</s3><sZ>2 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Naples</wicri:noRegion></affiliation></author><author><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A." last="Hauser">Robert A. 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KG</wicri:noRegion><wicri:noRegion>Ingelheim am Rhein</wicri:noRegion></affiliation></author><author><name sortKey="Debieuvre, Catherine" sort="Debieuvre, Catherine" uniqKey="Debieuvre C" first="Catherine" last="Debieuvre">Catherine Debieuvre</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Clinical Research Department, Boehringer Ingelheim France S.A.S.</s1><s2>Reims</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Reims</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0491630</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0491630 INIST</idno><idno type="RBID">Pascal:10-0491630</idno><idno type="wicri:Area/PascalFrancis/Corpus">000824</idno><idno type="wicri:Area/PascalFrancis/Curation">002495</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000A86</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, INSERM CIC9302-UMR825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Midi-Pyrénées</region></placeName><orgName type="university" n="3">Université Toulouse III - Paul Sabatier</orgName><orgName type="institution" wicri:auto="newGroup">Université de Toulouse</orgName></affiliation></author><author><name sortKey="Barone, Paolo" sort="Barone, Paolo" uniqKey="Barone P" first="Paolo" last="Barone">Paolo Barone</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurological Sciences, University of Naples</s1><s2>Naples</s2><s3>ITA</s3><sZ>2 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Naples</wicri:noRegion></affiliation></author><author><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A." last="Hauser">Robert A. Hauser</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Neurology, University of South Florida</s1><s2>Tampa, Florida</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region><settlement type="city">Tampa</settlement></placeName><orgName type="university">Université de Floride du Sud</orgName></affiliation></author><author><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology, Juntendo University School of Medicine</s1><s2>Bunkyo-ku, Tokyo</s2><s3>JPN</s3><sZ>4 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Neurology, Innsbruck Medical University</s1><s2>Innsbruck</s2><s3>AUT</s3><sZ>5 aut.</sZ></inist:fA14><country>Autriche</country><wicri:noRegion>Innsbruck</wicri:noRegion><placeName><settlement type="city">Innsbruck</settlement><region nuts="2" type="region">Tyrol (Land)</region></placeName><orgName type="university">Université de médecine d'Innsbruck</orgName></affiliation></author><author><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>University Department of Clinical Neurosciences, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Salin, Laurence" sort="Salin, Laurence" uniqKey="Salin L" first="Laurence" last="Salin">Laurence Salin</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Clinical Research Department, Boehringer Ingelheim France S.A.S.</s1><s2>Reims</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Reims</settlement></placeName></affiliation></author><author><name sortKey="Sohr, Mandy" sort="Sohr, Mandy" uniqKey="Sohr M" first="Mandy" last="Sohr">Mandy Sohr</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Medical Division, Boehringer Ingelheim Pharma GmbH & Co. KG</s1><s2>Ingelheim am Rhein</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Ingelheim am Rhein</wicri:noRegion><wicri:noRegion>Boehringer Ingelheim Pharma GmbH & Co. KG</wicri:noRegion><wicri:noRegion>Ingelheim am Rhein</wicri:noRegion></affiliation></author><author><name sortKey="Debieuvre, Catherine" sort="Debieuvre, Catherine" uniqKey="Debieuvre C" first="Catherine" last="Debieuvre">Catherine Debieuvre</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Clinical Research Department, Boehringer Ingelheim France S.A.S.</s1><s2>Reims</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Reims</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine agonist</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Pramipexole</term><term>Release</term><term>Safety</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Sécurité</term><term>Libération</term><term>Pramipexole</term><term>Stimulant dopaminergique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.SI%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>25</s2></fA05><fA06><s2>14</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease</s1></fA08><fA11 i1="01" i2="1"><s1>RASCOL (Olivier)</s1></fA11><fA11 i1="02" i2="1"><s1>BARONE (Paolo)</s1></fA11><fA11 i1="03" i2="1"><s1>HAUSER (Robert A.)</s1></fA11><fA11 i1="04" i2="1"><s1>MIZUNO (Yoshikuni)</s1></fA11><fA11 i1="05" i2="1"><s1>POEWE (Werner)</s1></fA11><fA11 i1="06" i2="1"><s1>SCHAPIRA (Anthony H. V.)</s1></fA11><fA11 i1="07" i2="1"><s1>SALIN (Laurence)</s1></fA11><fA11 i1="08" i2="1"><s1>SOHR (Mandy)</s1></fA11><fA11 i1="09" i2="1"><s1>DEBIEUVRE (Catherine)</s1></fA11><fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, INSERM CIC9302-UMR825</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Neurological Sciences, University of Naples</s1><s2>Naples</s2><s3>ITA</s3><sZ>2 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Neurology, University of South Florida</s1><s2>Tampa, Florida</s2><s3>USA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neurology, Juntendo University School of Medicine</s1><s2>Bunkyo-ku, Tokyo</s2><s3>JPN</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Neurology, Innsbruck Medical University</s1><s2>Innsbruck</s2><s3>AUT</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>University Department of Clinical Neurosciences, Institute of Neurology, University College London</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ></fA14><fA14 i1="07"><s1>Clinical Research Department, Boehringer Ingelheim France S.A.S.</s1><s2>Reims</s2><s3>FRA</s3><sZ>7 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="08"><s1>Medical Division, Boehringer Ingelheim Pharma GmbH & Co. KG</s1><s2>Ingelheim am Rhein</s2><s3>DEU</s3><sZ>8 aut.</sZ></fA14><fA17 i1="01" i2="1"><s1>Pramipexole Switch Study Group</s1><s3>INC</s3></fA17><fA20><s1>2326-2332</s1></fA20><fA21><s1>2010</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000192780100100</s5></fA43><fA44><s0>0000</s0><s1>© 2010 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>25 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>10-0491630</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.SI%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Sécurité</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Safety</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Seguridad</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Libération</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Release</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Liberación</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Pramipexole</s0><s2>NK</s2><s2>FR</s2><s5>11</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Pramipexole</s0><s2>NK</s2><s2>FR</s2><s5>11</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Pramipexol</s0><s2>NK</s2><s2>FR</s2><s5>11</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Stimulant dopaminergique</s0><s5>12</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Dopamine agonist</s0><s5>12</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Estimulante dopaminérgico</s0><s5>12</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fN21><s1>326</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Allemagne</li><li>Autriche</li><li>France</li><li>Italie</li><li>Japon</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Floride</li><li>Grand Londres</li><li>Midi-Pyrénées</li><li>Tyrol (Land)</li></region><settlement><li>Innsbruck</li><li>Londres</li><li>Reims</li><li>Tampa</li><li>Tokyo</li><li>Toulouse</li></settlement><orgName><li>Université Toulouse III - Paul Sabatier</li><li>Université de Floride du Sud</li><li>Université de Toulouse</li><li>Université de médecine d'Innsbruck</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></noRegion><name sortKey="Debieuvre, Catherine" sort="Debieuvre, Catherine" uniqKey="Debieuvre C" first="Catherine" last="Debieuvre">Catherine Debieuvre</name><name sortKey="Salin, Laurence" sort="Salin, Laurence" uniqKey="Salin L" first="Laurence" last="Salin">Laurence Salin</name></country><country name="Italie"><noRegion><name sortKey="Barone, Paolo" sort="Barone, Paolo" uniqKey="Barone P" first="Paolo" last="Barone">Paolo Barone</name></noRegion></country><country name="États-Unis"><region name="Floride"><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A." last="Hauser">Robert A. Hauser</name></region></country><country name="Japon"><noRegion><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name></noRegion></country><country name="Autriche"><region name="Tyrol (Land)"><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name></region></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. Schapira</name></region></country><country name="Allemagne"><noRegion><name sortKey="Sohr, Mandy" sort="Sohr, Mandy" uniqKey="Sohr M" first="Mandy" last="Sohr">Mandy Sohr</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Efficacy, Safety, and Tolerability of Overnight Switching from Immediate- to Once Daily Extended-Release Pramipexole in Early Parkinson's Disease
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