A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.
Identifieur interne : 000095 ( PubMed/Corpus ); précédent : 000094; suivant : 000096A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.
Auteurs : François Tison ; Charlotte Keywood ; Mark Wakefield ; Franck Durif ; Jean-Christophe Corvol ; Karla Eggert ; Mark Lew ; Stuart Isaacson ; Erwan Bezard ; Sonia-Maria Poli ; Christopher G. Goetz ; Claudia Trenkwalder ; Olivier RascolSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2016.
Abstract
The metabotropic glutamate receptor 5-negative allosteric modulator dipraglurant reduces levodopa-induced dyskinesia in the MPTP-macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa-induced dyskinesia in Parkinson's disease (PD).
DOI: 10.1002/mds.26659
PubMed: 27214664
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.</title><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. francois.tison@chu-bordeaux.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Keywood, Charlotte" sort="Keywood, Charlotte" uniqKey="Keywood C" first="Charlotte" last="Keywood">Charlotte Keywood</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Wakefield, Mark" sort="Wakefield, Mark" uniqKey="Wakefield M" first="Mark" last="Wakefield">Mark Wakefield</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eggert, Karla" sort="Eggert, Karla" uniqKey="Eggert K" first="Karla" last="Eggert">Karla Eggert</name><affiliation><nlm:affiliation>Universitätsklinikum Giessen und Marburg, Klinik für Neurologie, Marburg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Lew, Mark" sort="Lew, Mark" uniqKey="Lew M" first="Mark" last="Lew">Mark Lew</name><affiliation><nlm:affiliation>Department of Neurology USC/Keck School of Medicine, Los Angeles, California, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isaacson, Stuart" sort="Isaacson, Stuart" uniqKey="Isaacson S" first="Stuart" last="Isaacson">Stuart Isaacson</name><affiliation><nlm:affiliation>Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poli, Sonia Maria" sort="Poli, Sonia Maria" uniqKey="Poli S" first="Sonia-Maria" last="Poli">Sonia-Maria Poli</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G" last="Goetz">Christopher G. Goetz</name><affiliation><nlm:affiliation>Rush University Medical Center, Dept. of Neurological Sciences, Movement Disorder Section, Chicago, Illinois, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name><affiliation><nlm:affiliation>Paracelsus Elena Klinik, centre for Parkinson's Disease & Movement Disorders, Kassel, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27214664</idno><idno type="pmid">27214664</idno><idno type="doi">10.1002/mds.26659</idno><idno type="wicri:Area/PubMed/Corpus">000095</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000095</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.</title><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. francois.tison@chu-bordeaux.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Keywood, Charlotte" sort="Keywood, Charlotte" uniqKey="Keywood C" first="Charlotte" last="Keywood">Charlotte Keywood</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Wakefield, Mark" sort="Wakefield, Mark" uniqKey="Wakefield M" first="Mark" last="Wakefield">Mark Wakefield</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eggert, Karla" sort="Eggert, Karla" uniqKey="Eggert K" first="Karla" last="Eggert">Karla Eggert</name><affiliation><nlm:affiliation>Universitätsklinikum Giessen und Marburg, Klinik für Neurologie, Marburg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Lew, Mark" sort="Lew, Mark" uniqKey="Lew M" first="Mark" last="Lew">Mark Lew</name><affiliation><nlm:affiliation>Department of Neurology USC/Keck School of Medicine, Los Angeles, California, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isaacson, Stuart" sort="Isaacson, Stuart" uniqKey="Isaacson S" first="Stuart" last="Isaacson">Stuart Isaacson</name><affiliation><nlm:affiliation>Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poli, Sonia Maria" sort="Poli, Sonia Maria" uniqKey="Poli S" first="Sonia-Maria" last="Poli">Sonia-Maria Poli</name><affiliation><nlm:affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G" last="Goetz">Christopher G. Goetz</name><affiliation><nlm:affiliation>Rush University Medical Center, Dept. of Neurological Sciences, Movement Disorder Section, Chicago, Illinois, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name><affiliation><nlm:affiliation>Paracelsus Elena Klinik, centre for Parkinson's Disease & Movement Disorders, Kassel, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><nlm:affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The metabotropic glutamate receptor 5-negative allosteric modulator dipraglurant reduces levodopa-induced dyskinesia in the MPTP-macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa-induced dyskinesia in Parkinson's disease (PD).</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">27214664</PMID><DateCreated><Year>2016</Year><Month>09</Month><Day>07</Day></DateCreated><DateRevised><Year>2016</Year><Month>09</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>31</Volume><Issue>9</Issue><PubDate><Year>2016</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease.</ArticleTitle><Pagination><MedlinePgn>1373-80</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.26659</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The metabotropic glutamate receptor 5-negative allosteric modulator dipraglurant reduces levodopa-induced dyskinesia in the MPTP-macaque model. The objective of this study was to assess the safety, tolerability (primary objective), and efficacy (secondary objective) of dipraglurant on levodopa-induced dyskinesia in Parkinson's disease (PD).</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">The study was a phase 2A double-blind, placebo-controlled, randomized (2:1), 4-week, parallel-group, multicenter dose-escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa-induced dyskinesia. Safety and tolerability were assessed based on clinical and biological examination and adverse events recording. Secondary efficacy outcome measures included the modified Abnormal Involuntary Movement Scale, UPDRS, and diaries. Pharmacokinetics were measured at 3 visits following a single dose.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Fifty-two patients were exposed to dipraglurant and 24 to placebo. There were no major safety concerns. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%; P = 0.04) and on day 14 (100 mg, 32%; P =0 .04) and across a 3-hour postdose period on day 14 (P = 0.04). There was no evidence of worsening of parkinsonism. Dipraglurant was rapidly absorbed (tmax = 1 hour). The 100-mg dose led to a mean Cmax of 1844 ng/mL on day 28.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Dipraglurant proved to be safe and well tolerated in its first administration to PD patients. Its efficacy in reversing levodopa-induced dyskinesia warrants further investigations in a larger number of patients. © 2016 International Parkinson and Movement Disorder Society.</AbstractText><CopyrightInformation>© 2016 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tison</LastName><ForeName>François</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France. francois.tison@chu-bordeaux.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. francois.tison@chu-bordeaux.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Service de Neurologie, CHU de Bordeaux, Bordeaux, France. francois.tison@chu-bordeaux.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France. francois.tison@chu-bordeaux.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Keywood</LastName><ForeName>Charlotte</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wakefield</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durif</LastName><ForeName>Franck</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Neurology Service, A, Hôpital Gabriel Montpied, Clermont Ferrand, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Corvol</LastName><ForeName>Jean-Christophe</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sorbonne Universités and UPMC Univ Paris 06, INSERM UMRS-1127 and CIC-1422; CNRS UMR-7225; AP-HP; and ICM, Hôpital Pitié-Salpêtrière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eggert</LastName><ForeName>Karla</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Universitätsklinikum Giessen und Marburg, Klinik für Neurologie, Marburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lew</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurology USC/Keck School of Medicine, Los Angeles, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Isaacson</LastName><ForeName>Stuart</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bezard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poli</LastName><ForeName>Sonia-Maria</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Addex Pharma SA, Plan Les Ouates, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goetz</LastName><ForeName>Christopher G</ForeName><Initials>CG</Initials><AffiliationInfo><Affiliation>Rush University Medical Center, Dept. of Neurological Sciences, Movement Disorder Section, Chicago, Illinois, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trenkwalder</LastName><ForeName>Claudia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Paracelsus Elena Klinik, centre for Parkinson's Disease & Movement Disorders, Kassel, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>NS-Park/FCRIN Network, UMS 015, Toulouse, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CIC9302, Departments of Clinical Pharmacology and Neurosciences and NeuroToul COEN Center; INSERM, University Hospital of Toulouse and University of Toulouse 3, Toulouse, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>05</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">dipraglurant</Keyword><Keyword MajorTopicYN="N">levodopa-induced dyskinesia</Keyword><Keyword MajorTopicYN="N">mGluR5 antagonist</Keyword><Keyword MajorTopicYN="N">phase 2A</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>10</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>03</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>04</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>5</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>5</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>5</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27214664</ArticleId><ArticleId IdType="doi">10.1002/mds.26659</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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