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
Url:
DOI: 10.1002/mds.22922
Links to Exploration step
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<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>
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<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>
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<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, Clermont‐Ferrand, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Frank</namePart>
<namePart type="family">Durif</namePart>
<namePart type="termsOfAddress">MD, PhD</namePart>
<affiliation>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont‐Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845, Clermont‐Ferrand, France</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Monique</namePart>
<namePart type="family">Galitzky</namePart>
<namePart type="termsOfAddress">MD</namePart>
<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>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Jean‐Marie</namePart>
<namePart 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>
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<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>
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<languageTerm type="code" authority="iso639-2b">eng</languageTerm>
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<extent unit="figures">3</extent>
<extent unit="tables">3</extent>
<extent unit="references">27</extent>
<extent unit="words">5426</extent>
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<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>
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<recordContentSource>WILEY</recordContentSource>
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