A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics
Identifieur interne : 000217 ( Main/Corpus ); précédent : 000216; suivant : 000218A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics
Auteurs : C. Warren Olanow ; Robert A. Hauser ; Joseph Jankovic ; William Langston ; Anthony Lang ; Werner Poewe ; Eduardo Tolosa ; Fabrizio Stocchi ; Eldad Melamed ; Eli Eyal ; Olivier RascolSource :
- Movement Disorders [ 0885-3185 ] ; 2008-11-15.
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Abstract
A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society
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DOI: 10.1002/mds.22218
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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="2194">2194</biblScope><biblScope unit="page" to="2201">2201</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">9028D8D08AB9F4F0E5A22149A3E88C34D86155B2</idno><idno type="DOI">10.1002/mds.22218</idno><idno type="ArticleID">MDS22218</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>delayed start design</term><term>disease modification</term><term>neuroprotection</term><term>rasagiline</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>C. Warren Olanow MD</name><affiliations><json:string>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Robert A. Hauser MD</name><affiliations><json:string>Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA</json:string></affiliations></json:item><json:item><name>Joseph Jankovic MD</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</json:string></affiliations></json:item><json:item><name>William Langston MD</name><affiliations><json:string>The Parkinson's Institute, Sunnyvale, California, USA</json:string></affiliations></json:item><json:item><name>Anthony Lang MD</name><affiliations><json:string>Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>Werner Poewe MD</name><affiliations><json:string>Department of Neurology, Innsbruck Medical University, Innsbruck, Austria</json:string></affiliations></json:item><json:item><name>Eduardo Tolosa MD</name><affiliations><json:string>Movement Disorder Unit, Neurology Service, Hospital Clinic, University of Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Fabrizio Stocchi MD</name><affiliations><json:string>Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy</json:string></affiliations></json:item><json:item><name>Eldad Melamed MD</name><affiliations><json:string>Department of Neurology, Rabin Medical Center, Beilinson campus, Petah Tikva and Sackler, School of Medicine, Tel Aviv University, Israel</json:string></affiliations></json:item><json:item><name>Eli Eyal PhD</name><affiliations><json:string>Global Statistics Unit, Teva Pharmaceutical Industries Ltd, Israel</json:string></affiliations></json:item><json:item><name>Olivier Rascol MD</name><affiliations><json:string>INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculté de Médecine, Toulouse, France</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>delayed start design</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>rasagiline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neuroprotection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>disease modification</value></json:item></subject><articleId><json:string>MDS22218</json:string></articleId><language><json:string>eng</json:string></language><abstract>A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society</abstract><qualityIndicators><score>7.904</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1512</abstractCharCount><pdfWordCount>5003</pdfWordCount><pdfCharCount>32589</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>242</abstractWordCount></qualityIndicators><title>A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics</title><genre><json:string>article</json:string></genre><host><volume>23</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>8</total><last>2201</last><first>2194</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.22218</json:string></doi><id>9028D8D08AB9F4F0E5A22149A3E88C34D86155B2</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/9028D8D08AB9F4F0E5A22149A3E88C34D86155B2/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/9028D8D08AB9F4F0E5A22149A3E88C34D86155B2/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/9028D8D08AB9F4F0E5A22149A3E88C34D86155B2/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics</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">*Potential conflict of interest: Dr. Eyal is an employee of Teva, and all other authors have served as consultants to Teva. Dr. Olanow has served as a consultant for for Novartis, BI, Solvay, Ceregene, and Merck Second. Dr. Hauser has received honoraria or consulting fees from Allergan, Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Biovail, Centopharm, Cephalon, CombinatoRx, Daiichi, Eisai Ltd, Elan, EMD Serono, GE Healthcare, Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Merz Pharmaceuticals, Novartis, Ortho McNeil , Ovation Pharmaceuticals, Penwest Pharmaceuticals, Pfizer, Pharmacia, Prestwick, Schwarz Pharma, Schering, Skye Pharma, SmithKline Beecham, Solstice Neurosciences, Solvay, Synosia, UCB Pharmaceuticals, United BioScource, Upsher‐Smith Laboratories, Valeant, Vernalis and XenoPort. Dr. Langston, Dr. Poewe , Dr. Tolosa, Dr. Rascol has received honoraria for advising drug companies with interest in the field of neuroprotection in Parkinson's disease (Eli‐Lilly, Lundbeck, Novartis, Boehringer‐Ingelheim) and has received unrestricted financial support for research programs from the same companies.</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>TEVA Pharmaceutical Industries (Israel)</note><note>Teva Neuroscience Inc. (USA)</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics</title><author><persName><forename type="first">C. Warren</forename><surname>Olanow</surname></persName><roleName type="degree">MD</roleName><note type="correspondence"><p>Correspondence: Department of Neurology, Mount Sinai School of Medicine, Annenberg 14‐73, 1 Gustave L. Levy Place, New York, NY 10029</p></note><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation></author><author><persName><forename type="first">Robert A.</forename><surname>Hauser</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA</affiliation></author><author><persName><forename type="first">Joseph</forename><surname>Jankovic</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation></author><author><persName><forename type="first">William</forename><surname>Langston</surname></persName><roleName type="degree">MD</roleName><affiliation>The Parkinson's Institute, Sunnyvale, California, USA</affiliation></author><author><persName><forename type="first">Anthony</forename><surname>Lang</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada</affiliation></author><author><persName><forename type="first">Werner</forename><surname>Poewe</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Innsbruck Medical University, Innsbruck, Austria</affiliation></author><author><persName><forename type="first">Eduardo</forename><surname>Tolosa</surname></persName><roleName type="degree">MD</roleName><affiliation>Movement Disorder Unit, Neurology Service, Hospital Clinic, University of Barcelona, Spain</affiliation></author><author><persName><forename type="first">Fabrizio</forename><surname>Stocchi</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy</affiliation></author><author><persName><forename type="first">Eldad</forename><surname>Melamed</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Rabin Medical Center, Beilinson campus, Petah Tikva and Sackler, School of Medicine, Tel Aviv University, Israel</affiliation></author><author><persName><forename type="first">Eli</forename><surname>Eyal</surname></persName><roleName type="degree">PhD</roleName><affiliation>Global Statistics Unit, Teva Pharmaceutical Industries Ltd, Israel</affiliation></author><author><persName><forename type="first">Olivier</forename><surname>Rascol</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculté de Médecine, Toulouse, France</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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Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 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>delayed start design</term></item><item><term>rasagiline</term></item><item><term>neuroprotection</term></item><item><term>disease modification</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="2007-12-21">Received</change><change when="2008-06-16">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/9028D8D08AB9F4F0E5A22149A3E88C34D86155B2/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. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="150"><doi origin="wiley" registered="yes">10.1002/mds.v23:15</doi><numberingGroup><numbering type="journalVolume" number="23">23</numbering><numbering type="journalIssue">15</numbering></numberingGroup><coverDate startDate="2008-11-15">15 November 2008</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="80" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.22218</doi><idGroup><id type="unit" value="MDS22218"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2008 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2007-12-21"></event><event type="manuscriptRevised" date="2008-03-06"></event><event type="manuscriptAccepted" date="2008-06-16"></event><event type="publishedOnlineEarlyUnpaginated" date="2008-10-19"></event><event type="firstOnline" date="2008-10-19"></event><event type="publishedOnlineFinalForm" date="2008-11-24"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-09"></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">2194</numbering><numbering type="pageLast">2201</numbering></numberingGroup><correspondenceTo>Department of Neurology, Mount Sinai School of Medicine, Annenberg 14‐73, 1 Gustave L. Levy Place, New York, NY 10029</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS22218.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="1"></count><count type="referenceTotal" number="56"></count><count type="wordTotal" number="5369"></count></countGroup><titleGroup><title type="main" xml:lang="en">A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics<link href="#fn1"></link> <link href="#fn2"></link></title><title type="short" xml:lang="en">Rasagiline as a Disease Modifying Therapy in PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>C. Warren</givenNames><familyName>Olanow</familyName><degrees>MD</degrees></personName><contactDetails><email>warren.olanow@mssm.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Robert A.</givenNames><familyName>Hauser</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Joseph</givenNames><familyName>Jankovic</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>William</givenNames><familyName>Langston</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Anthony</givenNames><familyName>Lang</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Werner</givenNames><familyName>Poewe</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Eduardo</givenNames><familyName>Tolosa</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Fabrizio</givenNames><familyName>Stocchi</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Eldad</givenNames><familyName>Melamed</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Eli</givenNames><familyName>Eyal</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af11"><personName><givenNames>Olivier</givenNames><familyName>Rascol</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>The Parkinson's Institute, Sunnyvale, California, USA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="CA" type="organization"><unparsedAffiliation>Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="AT" type="organization"><unparsedAffiliation>Department of Neurology, Innsbruck Medical University, Innsbruck, Austria</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="ES" type="organization"><unparsedAffiliation>Movement Disorder Unit, Neurology Service, Hospital Clinic, University of Barcelona, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="IT" type="organization"><unparsedAffiliation>Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="IL" type="organization"><unparsedAffiliation>Department of Neurology, Rabin Medical Center, Beilinson campus, Petah Tikva and Sackler, School of Medicine, Tel Aviv University, Israel</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="IL" type="organization"><unparsedAffiliation>Global Statistics Unit, Teva Pharmaceutical Industries Ltd, Israel</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="FR" type="organization"><unparsedAffiliation>INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculté de Médecine, Toulouse, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">delayed start design</keyword><keyword xml:id="kwd3">rasagiline</keyword><keyword xml:id="kwd4">neuroprotection</keyword><keyword xml:id="kwd5">disease modification</keyword></keywordGroup><fundingInfo><fundingAgency>TEVA Pharmaceutical Industries (Israel)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Teva Neuroscience Inc. (USA)</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: Dr. Eyal is an employee of Teva, and all other authors have served as consultants to Teva. Dr. Olanow has served as a consultant for for Novartis, BI, Solvay, Ceregene, and Merck Second. Dr. Hauser has received honoraria or consulting fees from Allergan, Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Biovail, Centopharm, Cephalon, CombinatoRx, Daiichi, Eisai Ltd, Elan, EMD Serono, GE Healthcare, Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Merz Pharmaceuticals, Novartis, Ortho McNeil , Ovation Pharmaceuticals, Penwest Pharmaceuticals, Pfizer, Pharmacia, Prestwick, Schwarz Pharma, Schering, Skye Pharma, SmithKline Beecham, Solstice Neurosciences, Solvay, Synosia, UCB Pharmaceuticals, United BioScource, Upsher‐Smith Laboratories, Valeant, Vernalis and XenoPort. Dr. Langston, Dr. Poewe , Dr. Tolosa, Dr. Rascol has received honoraria for advising drug companies with interest in the field of neuroprotection in Parkinson's disease (Eli‐Lilly, Lundbeck, Novartis, Boehringer‐Ingelheim) and has received unrestricted financial support for research programs from the same companies. </p></note><note xml:id="fn2"><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></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Rasagiline as a Disease Modifying Therapy in PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A randomized, double‐blind, placebo‐controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): Rationale, design, and baseline characteristics</title></titleInfo><name type="personal"><namePart type="given">C. Warren</namePart><namePart type="family">Olanow</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation><description>Correspondence: Department of Neurology, Mount Sinai School of Medicine, Annenberg 14‐73, 1 Gustave L. Levy Place, New York, NY 10029</description><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>Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joseph</namePart><namePart type="family">Jankovic</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William</namePart><namePart type="family">Langston</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>The Parkinson's Institute, Sunnyvale, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anthony</namePart><namePart type="family">Lang</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Werner</namePart><namePart type="family">Poewe</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Innsbruck Medical University, Innsbruck, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eduardo</namePart><namePart type="family">Tolosa</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Movement Disorder Unit, Neurology Service, Hospital Clinic, University of Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Fabrizio</namePart><namePart type="family">Stocchi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eldad</namePart><namePart type="family">Melamed</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Rabin Medical Center, Beilinson campus, Petah Tikva and Sackler, School of Medicine, Tel Aviv University, Israel</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eli</namePart><namePart type="family">Eyal</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Global Statistics Unit, Teva Pharmaceutical Industries Ltd, Israel</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>INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculté de Médecine, Toulouse, France</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">2007-12-21</dateCaptured><dateValid encoding="w3cdtf">2008-06-16</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">2</extent><extent unit="tables">1</extent><extent unit="references">56</extent><extent unit="words">5369</extent></physicalDescription><abstract lang="en">A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial. © 2008 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: Dr. Eyal is an employee of Teva, and all other authors have served as consultants to Teva. Dr. Olanow has served as a consultant for for Novartis, BI, Solvay, Ceregene, and Merck Second. Dr. Hauser has received honoraria or consulting fees from Allergan, Bayer Schering Pharma AG, Bertek, Boehringer Ingelheim, Biovail, Centopharm, Cephalon, CombinatoRx, Daiichi, Eisai Ltd, Elan, EMD Serono, GE Healthcare, Genzyme, GlaxoSmithKline, Impax, Kyowa Pharmaceutical, Merck KgaA, Merz Pharmaceuticals, Novartis, Ortho McNeil , Ovation Pharmaceuticals, Penwest Pharmaceuticals, Pfizer, Pharmacia, Prestwick, Schwarz Pharma, Schering, Skye Pharma, SmithKline Beecham, Solstice Neurosciences, Solvay, Synosia, UCB Pharmaceuticals, United BioScource, Upsher‐Smith Laboratories, Valeant, Vernalis and XenoPort. Dr. Langston, Dr. Poewe , Dr. Tolosa, Dr. Rascol has received honoraria for advising drug companies with interest in the field of neuroprotection in Parkinson's disease (Eli‐Lilly, Lundbeck, Novartis, Boehringer‐Ingelheim) and has received unrestricted financial support for research programs from the same companies.</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="funding">TEVA Pharmaceutical Industries (Israel)</note><note type="funding">Teva Neuroscience Inc. (USA)</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>delayed start design</topic><topic>rasagiline</topic><topic>neuroprotection</topic><topic>disease modification</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. 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