Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials
Identifieur interne : 001544 ( Main/Corpus ); précédent : 001543; suivant : 001545Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials
Auteurs : Cristina Sampaio ; Juliana Bronzova ; Robert A. Hauser ; Anthony E. Lang ; Olivier Rascol ; Serge V. Van De Witte ; And Ad TheeuwesSource :
- Movement Disorders [ 0885-3185 ] ; 2011-07.
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Abstract
This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society
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DOI: 10.1002/mds.23590
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Van De Witte</name><affiliation><mods:affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Theeuwes, And Ad" sort="Theeuwes, And Ad" uniqKey="Theeuwes A" first="And Ad" last="Theeuwes">And Ad Theeuwes</name><affiliation><mods:affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-07">2011-07</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1464">1464</biblScope><biblScope unit="page" to="1476">1476</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">5F1B5BA930CAA821B9BFB5C07BFE579A366E4094</idno><idno type="DOI">10.1002/mds.23590</idno><idno type="ArticleID">MDS23590</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>pardoprunox (SLV308)</term><term>partial dopamine agonist</term><term>randomized controlled trial</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Cristina Sampaio MD, PhD</name><affiliations><json:string>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, Portugal</json:string></affiliations></json:item><json:item><name>Juliana Bronzova MD, DSc</name><affiliations><json:string>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</json:string></affiliations></json:item><json:item><name>Robert A. Hauser MD</name><affiliations><json:string>University of South Florida, Tampa, Florida, USA</json:string></affiliations></json:item><json:item><name>Anthony E. Lang MD</name><affiliations><json:string>Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Olivier Rascol MD</name><affiliations><json:string>Department of Clinical Pharmacology, Faculty of Medicine, University Hospital of Toulouse, Toulouse, France</json:string></affiliations></json:item><json:item><name>Serge V. van de Witte PhD</name><affiliations><json:string>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</json:string></affiliations></json:item><json:item><name>and Ad Theeuwes MSc</name><affiliations><json:string>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>pardoprunox (SLV308)</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>partial dopamine agonist</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>randomized controlled trial</value></json:item></subject><articleId><json:string>MDS23590</json:string></articleId><language><json:string>eng</json:string></language><abstract>This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>2001</abstractCharCount><pdfWordCount>6662</pdfWordCount><pdfCharCount>47074</pdfCharCount><pdfPageCount>13</pdfPageCount><abstractWordCount>284</abstractWordCount></qualityIndicators><title>Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials</title><corporate><json:item><name>for the Rembrandt/Vermeer Study Groups</name></json:item></corporate><genre><json:string>article</json:string></genre><host><volume>26</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>13</total><last>1476</last><first>1464</first></pages><issn><json:string>0885-3185</json:string></issn><issue>8</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/mds.23590</json:string></doi><id>5F1B5BA930CAA821B9BFB5C07BFE579A366E4094</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/5F1B5BA930CAA821B9BFB5C07BFE579A366E4094/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/5F1B5BA930CAA821B9BFB5C07BFE579A366E4094/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/5F1B5BA930CAA821B9BFB5C07BFE579A366E4094/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><notesStmt><note type="content">*Relevant conflicts of interest/financial disclosures: Cristina Sampaio is the chairperson of the permanent Steering Committee on the clinical development of pardoprunox and does not have any relevant personal financial interest to disclose. The research department to which Cristina Sampaio is affiliated has received research grants or fees from Astellas, Brane, Eisai, Fujisawa, Grünenthal, Kyowa, Lundbeck, Neurobiotech, Newron, Novartis, Schering‐Plough, Serono, Servier, Solvay, UCB, and Xytis. Juliana Bronzova, Serge V. van de Witte, and Ad Theeuwes are employees of Solvay Pharmaceuticals (Solvay is now Abbott). Robert A. Hauser has received honoraria or consulting fees from Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Centopharm, Eisai Ltd., Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Novartis, Ortho McNeil, Pfizer, Prestwick, Schwarz Pharma, Schering, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, Valeant, and Vernalis. Anthony E. Lang has received honoraria or consulting fees from Boehringer Ingelheim, Ceregene, Eisai, GlaxoSmithKline, Medtronic, Novartis, Prestwick, Solvay (member of the pardoprunox Development Steering Committee), Teva, and Valeant. Olivier Rascol has received scientific grants or consulting fees from Boehringer Ingelheim, Eisai Ltd., GlaxoSmithKline, Lundbeck, Novartis, Schering‐Plough, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, and UCB. Full financial disclosures and author roles may be found in the online version of this article.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials</title><author><orgName>for the Rembrandt/Vermeer Study Groups</orgName></author><author><persName><forename type="first">Cristina</forename><surname>Sampaio</surname></persName><roleName type="degree">MD, PhD</roleName><note type="correspondence"><p>Correspondence: Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Piso 3, Elevador 11, 1600 Lisboa, Portugal</p></note><affiliation>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, Portugal</affiliation></author><author><persName><forename type="first">Juliana</forename><surname>Bronzova</surname></persName><roleName type="degree">MD, DSc</roleName><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation></author><author><persName><forename type="first">Robert A.</forename><surname>Hauser</surname></persName><roleName type="degree">MD</roleName><affiliation>University of South Florida, Tampa, Florida, USA</affiliation></author><author><persName><forename type="first">Anthony E.</forename><surname>Lang</surname></persName><roleName type="degree">MD</roleName><affiliation>Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Olivier</forename><surname>Rascol</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Clinical Pharmacology, Faculty of Medicine, University Hospital of Toulouse, Toulouse, France</affiliation></author><author><persName><forename type="first">Serge V.</forename><surname>van de Witte</surname></persName><roleName type="degree">PhD</roleName><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation></author><author><persName><forename type="first">and Ad</forename><surname>Theeuwes</surname></persName><roleName type="degree">MSc</roleName><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-07"></date><biblScope unit="volume">26</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1464">1464</biblScope><biblScope unit="page" to="1476">1476</biblScope></imprint></monogr><idno type="istex">5F1B5BA930CAA821B9BFB5C07BFE579A366E4094</idno><idno type="DOI">10.1002/mds.23590</idno><idno type="ArticleID">MDS23590</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>pardoprunox (SLV308)</term></item><item><term>partial dopamine agonist</term></item><item><term>randomized controlled trial</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-07-14">Received</change><change when="2010-11-22">Registration</change><change when="2011-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/5F1B5BA930CAA821B9BFB5C07BFE579A366E4094/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="80"><doi origin="wiley" registered="yes">10.1002/mds.v26.8</doi><numberingGroup><numbering type="journalVolume" number="26">26</numbering><numbering type="journalIssue">8</numbering></numberingGroup><coverDate startDate="2011-07">July 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="170" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.23590</doi><idGroup><id type="unit" value="MDS23590"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2010-07-14"></event><event type="manuscriptRevised" date="2010-10-25"></event><event type="manuscriptAccepted" date="2010-11-22"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:3.0.1 mode:FullText" date="2011-12-15"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-05-03"></event><event type="publishedOnlineFinalForm" date="2011-07-21"></event><event type="firstOnline" date="2011-05-03"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">1464</numbering><numbering type="pageLast">1476</numbering></numberingGroup><correspondenceTo>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Piso 3, Elevador 11, 1600 Lisboa, Portugal</correspondenceTo><objectNameGroup><objectName elementName="appendix">Appendix</objectName></objectNameGroup><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS23590.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="5"></count><count type="referenceTotal" number="17"></count><count type="wordTotal" number="11735"></count></countGroup><titleGroup><title type="main" xml:lang="en">Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials<link href="#fn14"></link></title><title type="short" xml:lang="en">Pardoprunox in Early Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Cristina</givenNames><familyName>Sampaio</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>crissampaio@mail.telepac.pt</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Juliana</givenNames><familyName>Bronzova</familyName><degrees>MD, DSc</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Robert A.</givenNames><familyName>Hauser</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Anthony E.</givenNames><familyName>Lang</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Olivier</givenNames><familyName>Rascol</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Serge V.</givenNames><familyName>van de Witte</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af2"><personName><givenNames>and Ad</givenNames><familyName>Theeuwes</familyName><degrees>MSc</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af2"><groupName>for the Rembrandt/Vermeer Study Groups</groupName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="PT" type="organization"><unparsedAffiliation>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, Portugal</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="NL" type="organization"><unparsedAffiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>University of South Florida, Tampa, Florida, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="CA" type="organization"><unparsedAffiliation>Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="FR" type="organization"><unparsedAffiliation>Department of Clinical Pharmacology, Faculty of Medicine, University Hospital of Toulouse, Toulouse, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">pardoprunox (SLV308)</keyword><keyword xml:id="kwd3">partial dopamine agonist</keyword><keyword xml:id="kwd4">randomized controlled trial</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn14"><p><b>Relevant conflicts of interest/financial disclosures:</b> Cristina Sampaio is the chairperson of the permanent Steering Committee on the clinical development of pardoprunox and does not have any relevant personal financial interest to disclose. The research department to which Cristina Sampaio is affiliated has received research grants or fees from Astellas, Brane, Eisai, Fujisawa, Grünenthal, Kyowa, Lundbeck, Neurobiotech, Newron, Novartis, Schering‐Plough, Serono, Servier, Solvay, UCB, and Xytis. Juliana Bronzova, Serge V. van de Witte, and Ad Theeuwes are employees of Solvay Pharmaceuticals (Solvay is now Abbott). Robert A. Hauser has received honoraria or consulting fees from Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Centopharm, Eisai Ltd., Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Novartis, Ortho McNeil, Pfizer, Prestwick, Schwarz Pharma, Schering, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, Valeant, and Vernalis. Anthony E. Lang has received honoraria or consulting fees from Boehringer Ingelheim, Ceregene, Eisai, GlaxoSmithKline, Medtronic, Novartis, Prestwick, Solvay (member of the pardoprunox Development Steering Committee), Teva, and Valeant. Olivier Rascol has received scientific grants or consulting fees from Boehringer Ingelheim, Eisai Ltd., GlaxoSmithKline, Lundbeck, Novartis, Schering‐Plough, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, and UCB. Full financial disclosures and author roles may be found in the online version of this article.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Pardoprunox in Early Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Pardoprunox in early Parkinson's disease: Results from 2 large, randomized double‐blind trials</title></titleInfo><name type="personal"><namePart type="given">Cristina</namePart><namePart type="family">Sampaio</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, Portugal</affiliation><description>Correspondence: Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Piso 3, Elevador 11, 1600 Lisboa, Portugal</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Juliana</namePart><namePart type="family">Bronzova</namePart><namePart type="termsOfAddress">MD, DSc</namePart><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert A.</namePart><namePart type="family">Hauser</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of South Florida, Tampa, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anthony E.</namePart><namePart type="family">Lang</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olivier</namePart><namePart type="family">Rascol</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Clinical Pharmacology, Faculty of Medicine, University Hospital of Toulouse, Toulouse, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Serge V.</namePart><namePart type="family">van de Witte</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">and Ad</namePart><namePart type="family">Theeuwes</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Solvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="corporate"><namePart>for the Rembrandt/Vermeer Study Groups</namePart><description>Laboratório de Farmacologia Clinica e Terapêutica e Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Edifício do Hospital de Santa Maria, Lisboa, PortugalSolvay Pharmaceuticals B.V., (Solvay is now Abbott), Weesp, The NetherlandsUniversity of South Florida, Tampa, Florida, USAToronto Western Hospital, University of Toronto, Toronto, Ontario, CanadaDepartment of Clinical Pharmacology, Faculty of Medicine, University Hospital of Toulouse, Toulouse, France</description></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-07</dateIssued><dateCaptured encoding="w3cdtf">2010-07-14</dateCaptured><dateValid encoding="w3cdtf">2010-11-22</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">5</extent><extent unit="references">17</extent><extent unit="words">11735</extent></physicalDescription><abstract lang="en">This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, −6.0 and −4.7 points, respectively; flexible‐dose 12–42 mg/day, −5.5 points; placebo, −2.9 points; Vermeer—flexible‐dose 12–42 mg/day, −4.9 points; placebo, −2.5 points; pramipexole, −5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society</abstract><note type="content">*Relevant conflicts of interest/financial disclosures: Cristina Sampaio is the chairperson of the permanent Steering Committee on the clinical development of pardoprunox and does not have any relevant personal financial interest to disclose. The research department to which Cristina Sampaio is affiliated has received research grants or fees from Astellas, Brane, Eisai, Fujisawa, Grünenthal, Kyowa, Lundbeck, Neurobiotech, Newron, Novartis, Schering‐Plough, Serono, Servier, Solvay, UCB, and Xytis. Juliana Bronzova, Serge V. van de Witte, and Ad Theeuwes are employees of Solvay Pharmaceuticals (Solvay is now Abbott). Robert A. Hauser has received honoraria or consulting fees from Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Centopharm, Eisai Ltd., Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Novartis, Ortho McNeil, Pfizer, Prestwick, Schwarz Pharma, Schering, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, Valeant, and Vernalis. Anthony E. Lang has received honoraria or consulting fees from Boehringer Ingelheim, Ceregene, Eisai, GlaxoSmithKline, Medtronic, Novartis, Prestwick, Solvay (member of the pardoprunox Development Steering Committee), Teva, and Valeant. Olivier Rascol has received scientific grants or consulting fees from Boehringer Ingelheim, Eisai Ltd., GlaxoSmithKline, Lundbeck, Novartis, Schering‐Plough, Solvay (member of the pardoprunox Development Steering Committee), Teva Neuroscience, and UCB. Full financial disclosures and author roles may be found in the online version of this article.</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>pardoprunox (SLV308)</topic><topic>partial dopamine agonist</topic><topic>randomized controlled trial</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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