Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study
Identifieur interne : 000517 ( Istex/Corpus ); précédent : 000516; suivant : 000518Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study
Auteurs : Olivier Rascol ; Jean-Philippe Azulay ; Olivier Blin ; Anne-Marie Bonnet ; Christine Brefel-Courbon ; Pierre Césaro ; Philippe Damier ; Bérengère Debilly ; Frank Durif ; Monique Galitzky ; Jean-Marie Grouin ; Sylvie Pennaforte ; Gabriel Villafane ; Sadek Yaici ; Yves AgidSource :
- Movement Disorders [ 0885-3185 ] ; 2010-02-15.
English descriptors
Abstract
S90049, a novel sublingual formulation of the non‐ergoline D2‐D3 agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society
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DOI: 10.1002/mds.22922
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Azulay, Jean Hilippe" sort="Azulay, Jean Hilippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation><mods:affiliation>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Blin, 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Grouin</name><affiliation><mods:affiliation>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen, Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Pennaforte, Sylvie" sort="Pennaforte, Sylvie" uniqKey="Pennaforte S" first="Sylvie" last="Pennaforte">Sylvie Pennaforte</name><affiliation><mods:affiliation>Institut de Recherches Internationales Servier, Courbevoie, France</mods:affiliation></affiliation></author><author><name sortKey="Villafane, Gabriel" sort="Villafane, Gabriel" uniqKey="Villafane G" first="Gabriel" last="Villafane">Gabriel Villafane</name><affiliation><mods:affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</mods:affiliation></affiliation></author><author><name sortKey="Yaici, Sadek" sort="Yaici, Sadek" uniqKey="Yaici S" first="Sadek" last="Yaici">Sadek Yaici</name><affiliation><mods:affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:336E94F27649D97517D84497998FD3E90304F4EF</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/mds.22922</idno><idno type="url">https://api.istex.fr/document/336E94F27649D97517D84497998FD3E90304F4EF/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000517</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Azulay, Jean Hilippe" sort="Azulay, Jean Hilippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation><mods:affiliation>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Blin, Olivier" sort="Blin, Olivier" uniqKey="Blin O" first="Olivier" last="Blin">Olivier Blin</name><affiliation><mods:affiliation>Clinical Investigation Centre (CIC‐UPCET) and Department of Clinical Pharmacology, UMR‐CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Bonnet, Anne Arie" sort="Bonnet, Anne Arie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name><affiliation><mods:affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brefel Ourbon, Christine" sort="Brefel Ourbon, Christine" uniqKey="Brefel Ourbon C" first="Christine" last="Brefel-Courbon">Christine Brefel-Courbon</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Cesaro, Pierre" sort="Cesaro, Pierre" uniqKey="Cesaro P" first="Pierre" last="Césaro">Pierre Césaro</name><affiliation><mods:affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</mods:affiliation></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation><mods:affiliation>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes, Nantes, France</mods:affiliation></affiliation></author><author><name sortKey="Debilly, Berengere" sort="Debilly, Berengere" uniqKey="Debilly B" first="Bérengère" last="Debilly">Bérengère Debilly</name><affiliation><mods:affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</mods:affiliation></affiliation></author><author><name sortKey="Durif, Frank" sort="Durif, Frank" uniqKey="Durif F" first="Frank" last="Durif">Frank Durif</name><affiliation><mods:affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</mods:affiliation></affiliation></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Grouin, Jean Arie" sort="Grouin, Jean Arie" uniqKey="Grouin J" first="Jean-Marie" last="Grouin">Jean-Marie Grouin</name><affiliation><mods:affiliation>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen, Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Pennaforte, Sylvie" sort="Pennaforte, Sylvie" uniqKey="Pennaforte S" first="Sylvie" last="Pennaforte">Sylvie Pennaforte</name><affiliation><mods:affiliation>Institut de Recherches Internationales Servier, Courbevoie, France</mods:affiliation></affiliation></author><author><name sortKey="Villafane, Gabriel" sort="Villafane, Gabriel" uniqKey="Villafane G" first="Gabriel" last="Villafane">Gabriel Villafane</name><affiliation><mods:affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</mods:affiliation></affiliation></author><author><name sortKey="Yaici, Sadek" sort="Yaici, Sadek" uniqKey="Yaici S" first="Sadek" last="Yaici">Sadek Yaici</name><affiliation><mods:affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</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="2010-02-15">2010-02-15</date><biblScope unit="vol">25</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="368">368</biblScope><biblScope unit="page" to="376">376</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">336E94F27649D97517D84497998FD3E90304F4EF</idno><idno type="DOI">10.1002/mds.22922</idno><idno type="ArticleID">MDS22922</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>S90049</term><term>apomorphine</term><term>dopamine agonist</term><term>motor fluctuations</term><term>piribedil</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">S90049, a novel sublingual formulation of the non‐ergoline D2‐D3 agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Olivier Rascol MD, PhD</name><affiliations><json:string>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</json:string></affiliations></json:item><json:item><name>Jean‐Philippe Azulay MD</name><affiliations><json:string>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone, Marseille, France</json:string></affiliations></json:item><json:item><name>Olivier Blin MD, PhD</name><affiliations><json:string>Clinical Investigation Centre (CIC‐UPCET) and Department of Clinical Pharmacology, UMR‐CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone, Marseille, France</json:string></affiliations></json:item><json:item><name>Anne‐Marie Bonnet MD</name><affiliations><json:string>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</json:string></affiliations></json:item><json:item><name>Christine Brefel‐Courbon MD, PhD</name><affiliations><json:string>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</json:string></affiliations></json:item><json:item><name>Pierre Césaro MD</name><affiliations><json:string>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</json:string></affiliations></json:item><json:item><name>Philippe Damier MD, PhD</name><affiliations><json:string>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes, Nantes, France</json:string></affiliations></json:item><json:item><name>Bérengère Debilly MD</name><affiliations><json:string>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</json:string></affiliations></json:item><json:item><name>Frank Durif MD, PhD</name><affiliations><json:string>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</json:string></affiliations></json:item><json:item><name>Monique Galitzky MD</name><affiliations><json:string>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</json:string></affiliations></json:item><json:item><name>Jean‐Marie Grouin PhD</name><affiliations><json:string>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen, Rouen, France</json:string></affiliations></json:item><json:item><name>Sylvie Pennaforte MD</name><affiliations><json:string>Institut de Recherches Internationales Servier, Courbevoie, France</json:string></affiliations></json:item><json:item><name>Gabriel Villafane MD</name><affiliations><json:string>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</json:string></affiliations></json:item><json:item><name>Sadek Yaici MD</name><affiliations><json:string>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</json:string></affiliations></json:item><json:item><name>Yves Agid MD, PhD</name><affiliations><json:string>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, 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>motor fluctuations</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopamine agonist</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>piribedil</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>S90049</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>apomorphine</value></json:item></subject><language><json:string>eng</json:string></language><abstract>S90049, a novel sublingual formulation of the non‐ergoline D2‐D3 agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society</abstract><qualityIndicators><score>7.501</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1697</abstractCharCount><pdfWordCount>4501</pdfWordCount><pdfCharCount>28913</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>272</abstractWordCount></qualityIndicators><title>Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title><genre><json:string>Serial article</json:string></genre><host><volume>25</volume><pages><total>9</total><last>376</last><first>368</first></pages><issn><json:string>0885-3185</json:string></issn><issue>3</issue><subject><json:item><value>Research Article</value></json:item></subject><genre></genre><language><json:string>unknown</json:string></language><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/mds.22922</json:string></doi><id>336E94F27649D97517D84497998FD3E90304F4EF</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/336E94F27649D97517D84497998FD3E90304F4EF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/336E94F27649D97517D84497998FD3E90304F4EF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/336E94F27649D97517D84497998FD3E90304F4EF/fulltext/tei"><teiHeader type="text"><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Wiley Subscription Services, Inc., A Wiley Company</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note><note>IRIS, Institut de Recherches Internationales SERVIER, Courbevoie France</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title><author><persName><forename type="first">Olivier</forename><surname>Rascol</surname><roleName type="degree">MD, PhD</roleName></persName><note type="correspondence"><p>Correspondence: Department of Clinical Pharmacology, Faculty of Medicine, 37 Allées Jules Guesde, Toulouse 31000, France===</p></note><affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</affiliation></author><author><persName><forename type="first">Jean‐Philippe</forename><surname>Azulay</surname><roleName type="degree">MD</roleName></persName><affiliation>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone, Marseille, France</affiliation></author><author><persName><forename type="first">Olivier</forename><surname>Blin</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Clinical Investigation Centre (CIC‐UPCET) and Department of Clinical Pharmacology, UMR‐CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone, Marseille, France</affiliation></author><author><persName><forename type="first">Anne‐Marie</forename><surname>Bonnet</surname><roleName type="degree">MD</roleName></persName><affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Brefel‐Courbon</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</affiliation></author><author><persName><forename type="first">Pierre</forename><surname>Césaro</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</affiliation></author><author><persName><forename type="first">Philippe</forename><surname>Damier</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes, Nantes, France</affiliation></author><author><persName><forename type="first">Bérengère</forename><surname>Debilly</surname><roleName type="degree">MD</roleName></persName><affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</affiliation></author><author><persName><forename type="first">Frank</forename><surname>Durif</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</affiliation></author><author><persName><forename type="first">Monique</forename><surname>Galitzky</surname><roleName type="degree">MD</roleName></persName><affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, France</affiliation></author><author><persName><forename type="first">Jean‐Marie</forename><surname>Grouin</surname><roleName type="degree">PhD</roleName></persName><affiliation>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen, Rouen, France</affiliation></author><author><persName><forename type="first">Sylvie</forename><surname>Pennaforte</surname><roleName type="degree">MD</roleName></persName><affiliation>Institut de Recherches Internationales Servier, Courbevoie, France</affiliation></author><author><persName><forename type="first">Gabriel</forename><surname>Villafane</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</affiliation></author><author><persName><forename type="first">Sadek</forename><surname>Yaici</surname><roleName type="degree">MD</roleName></persName><affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</affiliation></author><author><persName><forename type="first">Yves</forename><surname>Agid</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-02-15"></date><biblScope unit="vol">25</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="368">368</biblScope><biblScope unit="page" to="376">376</biblScope></imprint></monogr><idno type="istex">336E94F27649D97517D84497998FD3E90304F4EF</idno><idno type="DOI">10.1002/mds.22922</idno><idno type="ArticleID">MDS22922</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>S90049, a novel sublingual formulation of the non‐ergoline D2‐D3 agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 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>motor fluctuations</term></item><item><term>dopamine agonist</term></item><item><term>piribedil</term></item><item><term>S90049</term></item><item><term>apomorphine</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="2009-08-27">Received</change><change when="2009-11-01">Registration</change><change when="2010-02-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/336E94F27649D97517D84497998FD3E90304F4EF/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="30"><doi origin="wiley" registered="yes">10.1002/mds.v25:3</doi><numberingGroup><numbering type="journalVolume" number="25">25</numbering><numbering type="journalIssue">3</numbering></numberingGroup><coverDate startDate="2010-02-15">15 February 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="170" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.22922</doi><idGroup><id type="unit" value="MDS22922"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2009 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2009-08-27"></event><event type="manuscriptRevised" date="2009-10-30"></event><event type="manuscriptAccepted" date="2009-11-01"></event><event type="firstOnline" date="2010-01-08"></event><event type="publishedOnlineFinalForm" date="2010-02-24"></event><event type="publishedOnlineAcceptedOrEarlyUnpaginated" date="2010-01-08"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:3.3.2 mode:FullText" date="2014-07-01"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.3.2 mode:FullText" date="2014-07-01"></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">368</numbering><numbering type="pageLast">376</numbering></numberingGroup><correspondenceTo>Department of Clinical Pharmacology, Faculty of Medicine, 37 Allées Jules Guesde, Toulouse 31000, France===</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS22922.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="27"></count><count type="wordTotal" number="5426"></count></countGroup><titleGroup><title type="main" xml:lang="en">Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study<link href="#fn5"></link></title><title type="short" xml:lang="en">S90049 on OFF Episodes in Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Olivier</givenNames><familyName>Rascol</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>rascol@cict.fr</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" 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affiliationRef="#af9"><personName><givenNames>Sylvie</givenNames><familyName>Pennaforte</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Gabriel</givenNames><familyName>Villafane</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Sadek</givenNames><familyName>Yaici</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Yves</givenNames><familyName>Agid</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC‐9302 and UMR‐825, CHU Toulouse‐Purpan and University Paul Sabatier, Toulouse, 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xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">motor fluctuations</keyword><keyword xml:id="kwd3">dopamine agonist</keyword><keyword xml:id="kwd4">piribedil</keyword><keyword xml:id="kwd5">S90049</keyword><keyword xml:id="kwd6">apomorphine</keyword></keywordGroup><fundingInfo><fundingAgency>IRIS, Institut de Recherches Internationales SERVIER, Courbevoie France</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>S90049, a novel sublingual formulation of the non‐ergoline D<sub>2</sub>‐D<sub>3</sub> agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], <i>P</i> = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, <i>P</i> = 0.03), time to turn ON (<i>P</i> = 0.013) and duration of the ON phase (<i>P</i> = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn5"><p>Potential conflict of interest: Nothing to report.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>S90049 on OFF Episodes in Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study</title></titleInfo><name type="personal"><namePart type="given">Olivier</namePart><namePart type="family">Rascol</namePart><namePart 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type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pierre</namePart><namePart type="family">Césaro</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philippe</namePart><namePart type="family">Damier</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes, Nantes, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bérengère</namePart><namePart type="family">Debilly</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, 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type="family">Grouin</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen, Rouen, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sylvie</namePart><namePart type="family">Pennaforte</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institut de Recherches Internationales Servier, Courbevoie, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gabriel</namePart><namePart type="family">Villafane</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor, Créteil 94000, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sadek</namePart><namePart type="family">Yaici</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yves</namePart><namePart type="family">Agid</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié‐Salpétrière, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-02-15</dateIssued><dateCaptured encoding="w3cdtf">2009-08-27</dateCaptured><dateValid encoding="w3cdtf">2009-11-01</dateValid><copyrightDate encoding="w3cdtf">2010</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">27</extent><extent unit="words">5426</extent></physicalDescription><abstract lang="en">S90049, a novel sublingual formulation of the non‐ergoline D2‐D3 agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (−13 ± 12 versus −7 ± 9 respectively; estimated difference −5.2, 95% Confidence Interval (CI)[−10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (−21.2 ± 10.1) and apomorphine (−23.6 ± 14.1) (estimated difference: 4.0 95% CI [−2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><note type="funding">IRIS, Institut de Recherches Internationales SERVIER, Courbevoie France</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>motor fluctuations</topic><topic>dopamine agonist</topic><topic>piribedil</topic><topic>S90049</topic><topic>apomorphine</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><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>2010</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>368</start><end>376</end><total>9</total></extent></part></relatedItem><identifier type="istex">336E94F27649D97517D84497998FD3E90304F4EF</identifier><identifier type="DOI">10.1002/mds.22922</identifier><identifier type="ArticleID">MDS22922</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study
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