Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations
Identifieur interne : 001C54 ( Main/Corpus ); précédent : 001C53; suivant : 001C55Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations
Auteurs : Robert A. Hauser ; Lisa M. Shulman ; Joel M. Trugman ; John W. Roberts ; Akihisa Mori ; Rocco Ballerini ; Neil M. SussmanSource :
- Movement Disorders [ 0885-3185 ] ; 2008-11-15.
English descriptors
Abstract
The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW‐6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society
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DOI: 10.1002/mds.22095
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ISTEX:D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4Le document en format XML
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Sussman</name><affiliation><mods:affiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</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="2008-11-15">2008-11-15</date><biblScope unit="volume">23</biblScope><biblScope unit="issue">15</biblScope><biblScope unit="page" from="2177">2177</biblScope><biblScope unit="page" to="2185">2185</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4</idno><idno type="DOI">10.1002/mds.22095</idno><idno type="ArticleID">MDS22095</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>KW‐6002</term><term>Parkinson's disease</term><term>istradefylline</term><term>motor fluctuations</term><term>off time</term><term>treatment</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW‐6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Robert A. Hauser MD</name><affiliations><json:string>Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Tampa, Florida, USA</json:string></affiliations></json:item><json:item><name>Lisa M. Shulman MD</name><affiliations><json:string>Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA</json:string></affiliations></json:item><json:item><name>Joel M. 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Sussman MD</name><affiliations><json:string>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>istradefylline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>KW‐6002</value></json:item><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>treatment</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>motor fluctuations</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>off time</value></json:item></subject><articleId><json:string>MDS22095</json:string></articleId><language><json:string>eng</json:string></language><abstract>The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW‐6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society</abstract><qualityIndicators><score>6.811</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1492</abstractCharCount><pdfWordCount>4291</pdfWordCount><pdfCharCount>27720</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>210</abstractWordCount></qualityIndicators><title>Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations</title><genre><json:string>article</json:string></genre><host><volume>23</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>9</total><last>2185</last><first>2177</first></pages><issn><json:string>0885-3185</json:string></issn><issue>15</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>2008</publicationDate><copyrightDate>2008</copyrightDate><doi><json:string>10.1002/mds.22095</json:string></doi><id>D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2008</date></publicationStmt><notesStmt><note type="content">*Disclosures: Drs. Hauser, Shulman, Trugman and Roberts' institutions received compensation from Kyowa Pharmaceutical, Inc. for their sites' conduct of the study. Drs. Hauser, Shulman, and Trugman have received honoraria, and consulting fees from Kyowa Pharmaceutical, Inc. Dr. Mori is an employee of Kyowa Hakko Kogyo Co., Ltd. Drs. Ballerini and Sussman are employees of Kyowa Pharmaceutical, Inc. Since completion of the study, Dr. Trugman has become an employee of Forest Laboratories, Inc.</note><note type="content">*Non‐sponsor Disclosures: Dr. 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, Teva Neuroscience, Valeant, and Vernalis. Dr. Trugman has received honoraria from GlaxoSmithKline. Dr. Shulman has received honoraria from Teva, Schwarz Pharma, and Boehringer Ingelheim.</note><note type="content">*The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing. (Movement Disordres Vol. 20., No. 12, 2005, p. 1536).</note><note type="content">*Members of the group “Istradefy line 6002‐US‐013 study group” are listed as an Appendix</note><note>Kyowa Pharmaceutical, Inc. (Princeton, NJ) - No. 6002‐US‐013;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations</title><author><persName><forename type="first">Robert A.</forename><surname>Hauser</surname></persName><roleName type="degree">MD</roleName><note type="correspondence"><p>Correspondence: Parkinson's Disease and Movement Disorders Center, University of South Florida, 4 Columbia Drive, Suite 410, Tampa, FL 33606</p></note><affiliation>Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Tampa, Florida, USA</affiliation></author><author><persName><forename type="first">Lisa M.</forename><surname>Shulman</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA</affiliation></author><author><persName><forename type="first">Joel M.</forename><surname>Trugman</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Virginia, Charlottesville, Virginia, USA</affiliation></author><author><persName><forename type="first">John W.</forename><surname>Roberts</surname></persName><roleName type="degree">MD</roleName><affiliation>Section of Neurology, Virginia Mason Medical Center, Seattle, Washington, USA</affiliation></author><author><persName><forename type="first">Akihisa</forename><surname>Mori</surname></persName><roleName type="degree">PhD</roleName><affiliation>Kyowa Hakko Kogyo Co., Ltd. Tokyo, Japan</affiliation></author><author><persName><forename type="first">Rocco</forename><surname>Ballerini</surname></persName><roleName type="degree">PhD</roleName><affiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</affiliation></author><author><persName><forename type="first">Neil M.</forename><surname>Sussman</surname></persName><roleName type="degree">MD</roleName><affiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. 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Istradefylline (KW‐6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>istradefylline</term></item><item><term>KW‐6002</term></item><item><term>Parkinson's disease</term></item><item><term>treatment</term></item><item><term>motor fluctuations</term></item><item><term>off time</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="2008-01-14">Received</change><change when="2008-04-01">Registration</change><change when="2008-11-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4/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="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. 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elementName="appendix">APPENDIX</objectName></objectNameGroup><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS22095.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="13"></count><count type="wordTotal" number="5842"></count></countGroup><titleGroup><title type="main" xml:lang="en">Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations<link href="#fn7"></link> <link href="#fn8"></link> <link href="#fn11"></link> <link href="#fn9"></link></title><title type="short" xml:lang="en">Study of Istradefylline in PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Robert A.</givenNames><familyName>Hauser</familyName><degrees>MD</degrees></personName><contactDetails><email>rhauser@health.usf.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Lisa M.</givenNames><familyName>Shulman</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Joel M.</givenNames><familyName>Trugman</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>John W.</givenNames><familyName>Roberts</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Akihisa</givenNames><familyName>Mori</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Rocco</givenNames><familyName>Ballerini</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Neil M.</givenNames><familyName>Sussman</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Tampa, Florida, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Virginia, Charlottesville, Virginia, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Section of Neurology, Virginia Mason Medical Center, Seattle, Washington, USA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="JP" type="organization"><unparsedAffiliation>Kyowa Hakko Kogyo Co., Ltd. Tokyo, Japan</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">istradefylline</keyword><keyword xml:id="kwd2">KW‐6002</keyword><keyword xml:id="kwd3">Parkinson's disease</keyword><keyword xml:id="kwd4">treatment</keyword><keyword xml:id="kwd5">motor fluctuations</keyword><keyword xml:id="kwd6">off time</keyword></keywordGroup><fundingInfo><fundingAgency>Kyowa Pharmaceutical, Inc. (Princeton, NJ)</fundingAgency><fundingNumber>6002‐US‐013</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW‐6002) is an adenosine A<sub>2A</sub> receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (<i>P</i> = 0.03) and 0.7 hours (<i>P</i> = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn7"><p>Disclosures: Drs. Hauser, Shulman, Trugman and Roberts' institutions received compensation from Kyowa Pharmaceutical, Inc. for their sites' conduct of the study. Drs. Hauser, Shulman, and Trugman have received honoraria, and consulting fees from Kyowa Pharmaceutical, Inc. Dr. Mori is an employee of Kyowa Hakko Kogyo Co., Ltd. Drs. Ballerini and Sussman are employees of Kyowa Pharmaceutical, Inc. Since completion of the study, Dr. Trugman has become an employee of Forest Laboratories, Inc.</p></note><note xml:id="fn8"><p>Non‐sponsor Disclosures: Dr. 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, Teva Neuroscience, Valeant, and Vernalis. Dr. Trugman has received honoraria from GlaxoSmithKline. Dr. Shulman has received honoraria from Teva, Schwarz Pharma, and Boehringer Ingelheim.</p></note><note xml:id="fn11"><p>The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing. (Movement Disordres Vol. 20., No. 12, 2005, p. 1536).</p></note><note xml:id="fn9"><p>Members of the group “Istradefy line 6002‐US‐013 study group” are listed as an <link href="#app1">Appendix</link></p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Study of Istradefylline in PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations</title></titleInfo><name type="personal"><namePart type="given">Robert A.</namePart><namePart type="family">Hauser</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Departments of Neurology, Molecular Pharmacology, and Physiology, University of South Florida, Tampa, Florida, USA</affiliation><description>Correspondence: Parkinson's Disease and Movement Disorders Center, University of South Florida, 4 Columbia Drive, Suite 410, Tampa, FL 33606</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lisa M.</namePart><namePart type="family">Shulman</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joel M.</namePart><namePart type="family">Trugman</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Virginia, Charlottesville, Virginia, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John W.</namePart><namePart type="family">Roberts</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Section of Neurology, Virginia Mason Medical Center, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Akihisa</namePart><namePart type="family">Mori</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Kyowa Hakko Kogyo Co., Ltd. Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rocco</namePart><namePart type="family">Ballerini</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Neil M.</namePart><namePart type="family">Sussman</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Kyowa Pharmaceutical, Inc., Princeton, New Jersey, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></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">2008-11-15</dateIssued><dateCaptured encoding="w3cdtf">2008-01-14</dateCaptured><dateValid encoding="w3cdtf">2008-04-01</dateValid><copyrightDate encoding="w3cdtf">2008</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">3</extent><extent unit="tables">3</extent><extent unit="references">13</extent><extent unit="words">5842</extent></physicalDescription><abstract lang="en">The objective of this study was to evaluate the efficacy, safety, and tolerability of istradefylline 20 mg once daily versus placebo as an adjunct to levodopa in subjects with Parkinson's disease (PD) who have motor fluctuations. Istradefylline (KW‐6002) is an adenosine A2A receptor antagonist that in primate models of PD improves motor function without causing or worsening dyskinesia. This 12‐week, multicenter, double‐blind, placebo‐controlled, randomized, Phase 3 study of istradefylline was conducted in subjects experiencing an average daily OFF time of at least 3 hours (116 randomized to istradefylline; 115 to placebo). All were on stable levodopa regimens; 90% were also on stable regimens of other anti‐Parkinson's medications. Istradefylline‐treated subjects had significant placebo‐corrected reductions in daily OFF time from baseline to endpoint: 4.6% (P = 0.03) and 0.7 hours (P = 0.03). For ON time with troublesome dyskinesia, the changes between istradefylline and placebo were not significant. Istradefylline was well tolerated, with 6 (5.2%) istradefylline‐treated and 7 (6.1%) placebo‐treated subjects withdrawing from the study because of adverse events. Dyskinesia, lightheadedness, tremor, constipation, and weight decrease were reported more often with istradefylline than placebo. We conclude that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations. © 2008 Movement Disorder Society</abstract><note type="content">*Disclosures: Drs. Hauser, Shulman, Trugman and Roberts' institutions received compensation from Kyowa Pharmaceutical, Inc. for their sites' conduct of the study. Drs. Hauser, Shulman, and Trugman have received honoraria, and consulting fees from Kyowa Pharmaceutical, Inc. Dr. Mori is an employee of Kyowa Hakko Kogyo Co., Ltd. Drs. Ballerini and Sussman are employees of Kyowa Pharmaceutical, Inc. Since completion of the study, Dr. Trugman has become an employee of Forest Laboratories, Inc.</note><note type="content">*Non‐sponsor Disclosures: Dr. 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, Teva Neuroscience, Valeant, and Vernalis. Dr. Trugman has received honoraria from GlaxoSmithKline. Dr. Shulman has received honoraria from Teva, Schwarz Pharma, and Boehringer Ingelheim.</note><note type="content">*The authors have confirmed with the Editor that their work complies with the Journal's Editorial policy on ghost‐writing. (Movement Disordres Vol. 20., No. 12, 2005, p. 1536).</note><note type="content">*Members of the group “Istradefy line 6002‐US‐013 study group” are listed as an Appendix</note><note type="funding">Kyowa Pharmaceutical, Inc. (Princeton, NJ) - No. 6002‐US‐013; </note><subject lang="en"><genre>Keywords</genre><topic>istradefylline</topic><topic>KW‐6002</topic><topic>Parkinson's disease</topic><topic>treatment</topic><topic>motor fluctuations</topic><topic>off time</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>23</number></detail><detail type="issue"><caption>no.</caption><number>15</number></detail><extent unit="pages"><start>2177</start><end>2185</end><total>9</total></extent></part></relatedItem><identifier type="istex">D16EBA1B882CDB4F40CD3FAF655B95EF7EB56DD4</identifier><identifier type="DOI">10.1002/mds.22095</identifier><identifier type="ArticleID">MDS22095</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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