Orodispersible Sublingual Piribedil to Abort OFF Episodes: A Single Dose Placebo-Controlled, Randomized, Double-Blind, Cross-Over Study
Identifieur interne : 002089 ( PascalFrancis/Curation ); précédent : 002088; suivant : 002090Orodispersible Sublingual Piribedil to Abort OFF Episodes: A Single Dose Placebo-Controlled, Randomized, Double-Blind, Cross-Over Study
Auteurs : Olivier Rascol [France] ; Jean-Philippe Azulay [France] ; Olivier Blin [France] ; Anne-Marie Bonnet [France] ; Christine Brefel-Courbon [France] ; Pierre Cesaro [France] ; Philippe Damier [France] ; Bérengère Debilly [France] ; Frank Durif [France] ; Monique Galitzky [France] ; Jean-Marie Grouin [France] ; Sylvie Pennaforte [France] ; Gabriel Villafane [France] ; Sadek Yaici [France] ; Yves Agid [France]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
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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 was superior 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.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">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 wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Azulay, Jean Philippe" sort="Azulay, Jean Philippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, 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last="Durif">Frank Durif</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845</s1><s2>Clermont-Ferrand</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Grouin, Jean Marie" sort="Grouin, Jean Marie" uniqKey="Grouin J" first="Jean-Marie" last="Grouin">Jean-Marie Grouin</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen</s1><s2>Rouen</s2><s3>FRA</s3><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Pennaforte, Sylvie" sort="Pennaforte, Sylvie" uniqKey="Pennaforte S" first="Sylvie" last="Pennaforte">Sylvie Pennaforte</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Institut de Recherches Internationales Servier</s1><s2>Courbevoie</s2><s3>FRA</s3><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Villafane, Gabriel" sort="Villafane, Gabriel" uniqKey="Villafane G" first="Gabriel" last="Villafane">Gabriel Villafane</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor</s1><s2>Créteil 94000</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Yaici, Sadek" sort="Yaici, Sadek" uniqKey="Yaici S" first="Sadek" last="Yaici">Sadek Yaici</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>France</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0161577</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0161577 INIST</idno><idno type="RBID">Pascal:10-0161577</idno><idno type="wicri:Area/PascalFrancis/Corpus">000C30</idno><idno type="wicri:Area/PascalFrancis/Curation">002089</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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 wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Azulay, Jean Philippe" sort="Azulay, Jean Philippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>2 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Blin, Olivier" sort="Blin, Olivier" uniqKey="Blin O" first="Olivier" last="Blin">Olivier Blin</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Clinical Investigation Centre (CIC-UPCET) and Department of Clinical Pharmacology, UMR-CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Bonnet, Anne Marie" sort="Bonnet, Anne Marie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Brefel Courbon, Christine" sort="Brefel Courbon, Christine" uniqKey="Brefel Courbon C" first="Christine" last="Brefel-Courbon">Christine Brefel-Courbon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Cesaro, Pierre" sort="Cesaro, Pierre" uniqKey="Cesaro P" first="Pierre" last="Cesaro">Pierre Cesaro</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor</s1><s2>Créteil 94000</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes</s1><s2>Nantes</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Debilly, Berengere" sort="Debilly, Berengere" uniqKey="Debilly B" first="Bérengère" last="Debilly">Bérengère Debilly</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845</s1><s2>Clermont-Ferrand</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Durif, Frank" sort="Durif, Frank" uniqKey="Durif F" first="Frank" last="Durif">Frank Durif</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845</s1><s2>Clermont-Ferrand</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Grouin, Jean Marie" sort="Grouin, Jean Marie" uniqKey="Grouin J" first="Jean-Marie" last="Grouin">Jean-Marie Grouin</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen</s1><s2>Rouen</s2><s3>FRA</s3><sZ>11 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Pennaforte, Sylvie" sort="Pennaforte, Sylvie" uniqKey="Pennaforte S" first="Sylvie" last="Pennaforte">Sylvie Pennaforte</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Institut de Recherches Internationales Servier</s1><s2>Courbevoie</s2><s3>FRA</s3><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Villafane, Gabriel" sort="Villafane, Gabriel" uniqKey="Villafane G" first="Gabriel" last="Villafane">Gabriel Villafane</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor</s1><s2>Créteil 94000</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Yaici, Sadek" sort="Yaici, Sadek" uniqKey="Yaici S" first="Sadek" last="Yaici">Sadek Yaici</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>France</country></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine agonist</term><term>Double blind study</term><term>Fluctuations</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Piribedil</term><term>Placebo</term><term>Single dose</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Piribédil</term><term>Dose unique</term><term>Placebo</term><term>Etude double insu</term><term>Fluctuation</term><term>Stimulant dopaminergique</term><term>Apomorphine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 was superior 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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>25</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Orodispersible Sublingual Piribedil to Abort OFF Episodes: A Single Dose Placebo-Controlled, Randomized, Double-Blind, Cross-Over Study</s1></fA08><fA11 i1="01" i2="1"><s1>RASCOL (Olivier)</s1></fA11><fA11 i1="02" i2="1"><s1>AZULAY (Jean-Philippe)</s1></fA11><fA11 i1="03" i2="1"><s1>BLIN (Olivier)</s1></fA11><fA11 i1="04" i2="1"><s1>BONNET (Anne-Marie)</s1></fA11><fA11 i1="05" i2="1"><s1>BREFEL-COURBON (Christine)</s1></fA11><fA11 i1="06" i2="1"><s1>CESARO (Pierre)</s1></fA11><fA11 i1="07" i2="1"><s1>DAMIER (Philippe)</s1></fA11><fA11 i1="08" i2="1"><s1>DEBILLY (Bérengère)</s1></fA11><fA11 i1="09" i2="1"><s1>DURIF (Frank)</s1></fA11><fA11 i1="10" i2="1"><s1>GALITZKY (Monique)</s1></fA11><fA11 i1="11" i2="1"><s1>GROUIN (Jean-Marie)</s1></fA11><fA11 i1="12" i2="1"><s1>PENNAFORTE (Sylvie)</s1></fA11><fA11 i1="13" i2="1"><s1>VILLAFANE (Gabriel)</s1></fA11><fA11 i1="14" i2="1"><s1>YAICI (Sadek)</s1></fA11><fA11 i1="15" i2="1"><s1>AGID (Yves)</s1></fA11><fA14 i1="01"><s1>Departments of Clinical Pharmacology and Neurosciences, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>Service de Neurologie et Pathologie du Mouvement, Pôle Neurosciences cliniques, CHU Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>2 aut.</sZ></fA14><fA14 i1="03"><s1>Clinical Investigation Centre (CIC-UPCET) and Department of Clinical Pharmacology, UMR-CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>Centre d'Investigation Clinique, Fédération des maladies du Système Nerveux, INSERM U 679, CHU Pitié-Salpétrière</s1><s2>Paris</s2><s3>FRA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Clinical Neurosciences, INSERM U 841, CHU Henri Mondor</s1><s2>Créteil 94000</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="06"><s1>INSERM, Clinical Investigation Center CIC, and Clinique Neurologique, CHU Nantes</s1><s2>Nantes</s2><s3>FRA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="07"><s1>Service de Neurologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Faculty of Medecine, University of Clermont, 1, EA 3845</s1><s2>Clermont-Ferrand</s2><s3>FRA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="08"><s1>Laboratoire de Biostatistiques, INSERM U 657, Université de Rouen</s1><s2>Rouen</s2><s3>FRA</s3><sZ>11 aut.</sZ></fA14><fA14 i1="09"><s1>Institut de Recherches Internationales Servier</s1><s2>Courbevoie</s2><s3>FRA</s3><sZ>12 aut.</sZ></fA14><fA20><s1>368-376</s1></fA20><fA21><s1>2010</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000181820230160</s5></fA43><fA44><s0>0000</s0><s1>© 2010 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>27 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>10-0161577</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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 was superior 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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B02Q</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Piribédil</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Piribedil</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Piribedil</s0><s2>NK</s2><s2>FR</s2><s5>09</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Dose unique</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Single dose</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Dosis única</s0><s5>10</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Placebo</s0><s5>11</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Placebo</s0><s5>11</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Placebo</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Etude double insu</s0><s5>12</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Double blind study</s0><s5>12</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Estudio doble ciego</s0><s5>12</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Fluctuation</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Fluctuations</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Fluctuación</s0><s5>13</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Stimulant dopaminergique</s0><s5>14</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Dopamine agonist</s0><s5>14</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Estimulante dopaminérgico</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Apomorphine</s0><s2>NK</s2><s2>FR</s2><s5>15</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fN21><s1>102</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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