Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease
Identifieur interne : 002163 ( Main/Corpus ); précédent : 002162; suivant : 002164Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease
Auteurs : Robert A. Hauser ; Aaron L. Ellenbogen ; Leo Verhagen Metman ; Ann Hsu ; Martin J. O'Connell ; Nishit B. Modi ; Hsuan-Ming Yao ; Sherron H. Kell ; Suneel K. GuptaSource :
- Movement Disorders [ 0885-3185 ] ; 2011-10.
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- KwdEn :
Abstract
The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended‐release formulation of carbidopa‐levodopa, with an immediate‐release carbidopa‐levodopa formulation in advanced Parkinson's disease. We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (P < .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa Cmax was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society
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DOI: 10.1002/mds.23861
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Kell</name><affiliation><mods:affiliation>Impax Pharmaceuticals, Hayward, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Gupta, Suneel K" sort="Gupta, Suneel K" uniqKey="Gupta S" first="Suneel K." last="Gupta">Suneel K. Gupta</name><affiliation><mods:affiliation>Impax Pharmaceuticals, Hayward, California, USA</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="2011-10">2011-10</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2246">2246</biblScope><biblScope unit="page" to="2252">2252</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">EFDD9E2393D829514DF101840BC3990DE713A5DF</idno><idno type="DOI">10.1002/mds.23861</idno><idno type="ArticleID">MDS23861</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>IPX066</term><term>Parkinson's disease</term><term>extended‐release levodopa</term><term>motor effects</term><term>motor fluctuations</term><term>pharmacokinetics</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended‐release formulation of carbidopa‐levodopa, with an immediate‐release carbidopa‐levodopa formulation in advanced Parkinson's disease. We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (P < .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa Cmax was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><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>Aaron L. Ellenbogen DO, MPH</name><affiliations><json:string>Michigan Institute for Neurological Disorders and Quest Research Institute, Farmington Hills, Michigan, USA</json:string></affiliations></json:item><json:item><name>Leo Verhagen Metman MD, PhD</name><affiliations><json:string>Rush University Medical Center, Chicago, Illinois, USA</json:string></affiliations></json:item><json:item><name>Ann Hsu PhD</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item><json:item><name>Martin J. O'Connell PhD</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item><json:item><name>Nishit B. Modi PhD</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item><json:item><name>Hsuan‐Ming Yao PhD</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item><json:item><name>Sherron H. Kell MD, MPH</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item><json:item><name>Suneel K. Gupta PhD</name><affiliations><json:string>Impax Pharmaceuticals, Hayward, California, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>IPX066</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>extended‐release levodopa</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>pharmacokinetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>motor effects</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>motor fluctuations</value></json:item></subject><articleId><json:string>MDS23861</json:string></articleId><language><json:string>eng</json:string></language><abstract>The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended‐release formulation of carbidopa‐levodopa, with an immediate‐release carbidopa‐levodopa formulation in advanced Parkinson's disease. We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (P > .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa Cmax was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society</abstract><qualityIndicators><score>6.919</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1713</abstractCharCount><pdfWordCount>3755</pdfWordCount><pdfCharCount>23515</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>222</abstractWordCount></qualityIndicators><title>Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>26</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>7</total><last>2252</last><first>2246</first></pages><issn><json:string>0885-3185</json:string></issn><issue>12</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.23861</json:string></doi><id>EFDD9E2393D829514DF101840BC3990DE713A5DF</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/EFDD9E2393D829514DF101840BC3990DE713A5DF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/EFDD9E2393D829514DF101840BC3990DE713A5DF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/EFDD9E2393D829514DF101840BC3990DE713A5DF/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease</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">*Clinicaltrials.gov Registry Number: NCT00869791</note><note type="content">*Funding agencies: This study was sponsored and funded by Impax Laboratories, Inc., acting through its Impax Pharmaceuticals division.</note><note type="content">*Relevant conflicts of interest/financial disclosures: Robert A. Hauser, Aaron L. Ellenbogen, and Leo Verhagen Metman have received fees for consulting and advisory board participation from Impax Laboratories, Inc. Ann Hsu, Hsuan‐Ming Yao, Sherron H. Kell, Nishit B. Modi, Martin J. O'Connell, and Suneel K. Gupta are employees of Impax Laboratories, Inc., and own stock in the company. The listed authors are the sole writers and contributors.</note><note type="content">*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">Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease</title><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">Aaron L.</forename><surname>Ellenbogen</surname></persName><roleName type="degree">DO, MPH</roleName><affiliation>Michigan Institute for Neurological Disorders and Quest Research Institute, Farmington Hills, Michigan, USA</affiliation></author><author><persName><forename type="first">Leo Verhagen</forename><surname>Metman</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Rush University Medical Center, Chicago, Illinois, USA</affiliation></author><author><persName><forename type="first">Ann</forename><surname>Hsu</surname></persName><roleName type="degree">PhD</roleName><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author><author><persName><forename type="first">Martin J.</forename><surname>O'Connell</surname></persName><roleName type="degree">PhD</roleName><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author><author><persName><forename type="first">Nishit B.</forename><surname>Modi</surname></persName><roleName type="degree">PhD</roleName><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author><author><persName><forename type="first">Hsuan‐Ming</forename><surname>Yao</surname></persName><roleName type="degree">PhD</roleName><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author><author><persName><forename type="first">Sherron H.</forename><surname>Kell</surname></persName><roleName type="degree">MD, MPH</roleName><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author><author><persName><forename type="first">Suneel K.</forename><surname>Gupta</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Impax Pharmaceuticals, 31047 Genstar Road, Hayward, CA 94544, USA</p></note><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. 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We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (P < .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa Cmax was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>IPX066</term></item><item><term>extended‐release levodopa</term></item><item><term>Parkinson's disease</term></item><item><term>pharmacokinetics</term></item><item><term>motor effects</term></item><item><term>motor fluctuations</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="2011-01-18">Received</change><change when="2011-06-08">Registration</change><change when="2011-10">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/EFDD9E2393D829514DF101840BC3990DE713A5DF/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. 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number="3"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="20"></count><count type="wordTotal" number="5012"></count></countGroup><titleGroup><title type="main" xml:lang="en">Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease<link href="#fn1"></link><link href="#fn2"></link><link href="#fn3"></link><link href="#fn4"></link></title><title type="short" xml:lang="en">IPX066 in Advanced PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Robert A.</givenNames><familyName>Hauser</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Aaron L.</givenNames><familyName>Ellenbogen</familyName><degrees>DO, MPH</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Leo Verhagen</givenNames><familyName>Metman</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Ann</givenNames><familyName>Hsu</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Martin J.</givenNames><familyName>O'Connell</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Nishit B.</givenNames><familyName>Modi</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Hsuan‐Ming</givenNames><familyName>Yao</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Sherron H.</givenNames><familyName>Kell</familyName><degrees>MD, MPH</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af4" corresponding="yes"><personName><givenNames>Suneel K.</givenNames><familyName>Gupta</familyName><degrees>PhD</degrees></personName><contactDetails><email>sgupta@impaxlabs.com</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, Florida, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Michigan Institute for Neurological Disorders and Quest Research Institute, Farmington Hills, Michigan, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Rush University Medical Center, Chicago, Illinois, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Impax Pharmaceuticals, Hayward, California, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">IPX066</keyword><keyword xml:id="kwd2">extended‐release levodopa</keyword><keyword xml:id="kwd3">Parkinson's disease</keyword><keyword xml:id="kwd4">pharmacokinetics</keyword><keyword xml:id="kwd5">motor effects</keyword><keyword xml:id="kwd6">motor fluctuations</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended‐release formulation of carbidopa‐levodopa, with an immediate‐release carbidopa‐levodopa formulation in advanced Parkinson's disease. We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (<i>P</i> < .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa <i>C</i><sub>max</sub> was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Clinicaltrials.gov Registry Number: NCT00869791</p></note><note xml:id="fn2"><p>Funding agencies: This study was sponsored and funded by Impax Laboratories, Inc., acting through its Impax Pharmaceuticals division.</p></note><note xml:id="fn3"><p>Relevant conflicts of interest/financial disclosures: Robert A. Hauser, Aaron L. Ellenbogen, and Leo Verhagen Metman have received fees for consulting and advisory board participation from Impax Laboratories, Inc. Ann Hsu, Hsuan‐Ming Yao, Sherron H. Kell, Nishit B. Modi, Martin J. O'Connell, and Suneel K. Gupta are employees of Impax Laboratories, Inc., and own stock in the company. The listed authors are the sole writers and contributors.</p></note><note xml:id="fn4"><p>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>Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>IPX066 in Advanced PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease</title></titleInfo><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">Aaron L.</namePart><namePart type="family">Ellenbogen</namePart><namePart type="termsOfAddress">DO, MPH</namePart><affiliation>Michigan Institute for Neurological Disorders and Quest Research Institute, Farmington Hills, Michigan, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Leo Verhagen</namePart><namePart type="family">Metman</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Rush University Medical Center, Chicago, Illinois, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ann</namePart><namePart type="family">Hsu</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin J.</namePart><namePart type="family">O'Connell</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nishit B.</namePart><namePart type="family">Modi</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hsuan‐Ming</namePart><namePart type="family">Yao</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sherron H.</namePart><namePart type="family">Kell</namePart><namePart type="termsOfAddress">MD, MPH</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Suneel K.</namePart><namePart type="family">Gupta</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Impax Pharmaceuticals, Hayward, California, USA</affiliation><description>Correspondence: Impax Pharmaceuticals, 31047 Genstar Road, Hayward, CA 94544, USA</description><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">2011-10</dateIssued><dateCaptured encoding="w3cdtf">2011-01-18</dateCaptured><dateValid encoding="w3cdtf">2011-06-08</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">3</extent><extent unit="tables">2</extent><extent unit="references">20</extent><extent unit="words">5012</extent></physicalDescription><abstract lang="en">The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended‐release formulation of carbidopa‐levodopa, with an immediate‐release carbidopa‐levodopa formulation in advanced Parkinson's disease. We performed an open‐label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate‐release carbidopa‐levodopa followed by IPX066 or IPX066 followed by immediate‐release carbidopa‐levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple‐dose administration). Following a single dose of IPX066 or immediate‐release carbidopa‐levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate‐release carbidopa‐levodopa (P < .0001). Multiple‐dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa Cmax was approximately 30% compared with immediate‐release carbidopa‐levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate‐release carbidopa‐levodopa. Larger, longer‐term, well‐controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066. © 2011 Movement Disorder Society</abstract><note type="content">*Clinicaltrials.gov Registry Number: NCT00869791</note><note type="content">*Funding agencies: This study was sponsored and funded by Impax Laboratories, Inc., acting through its Impax Pharmaceuticals division.</note><note type="content">*Relevant conflicts of interest/financial disclosures: Robert A. Hauser, Aaron L. Ellenbogen, and Leo Verhagen Metman have received fees for consulting and advisory board participation from Impax Laboratories, Inc. Ann Hsu, Hsuan‐Ming Yao, Sherron H. Kell, Nishit B. Modi, Martin J. O'Connell, and Suneel K. Gupta are employees of Impax Laboratories, Inc., and own stock in the company. The listed authors are the sole writers and contributors.</note><note type="content">*Full financial disclosures and author roles may be found in the online version of this article.</note><subject lang="en"><genre>Keywords</genre><topic>IPX066</topic><topic>extended‐release levodopa</topic><topic>Parkinson's disease</topic><topic>pharmacokinetics</topic><topic>motor effects</topic><topic>motor fluctuations</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></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>2011</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>2246</start><end>2252</end><total>7</total></extent></part></relatedItem><identifier type="istex">EFDD9E2393D829514DF101840BC3990DE713A5DF</identifier><identifier type="DOI">10.1002/mds.23861</identifier><identifier type="ArticleID">MDS23861</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 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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