Sarizotan as a treatment for dyskinesias in Parkinson's disease: A double‐blind placebo‐controlled trial
Identifieur interne : 000317 ( France/Analysis ); précédent : 000316; suivant : 000318Sarizotan as a treatment for dyskinesias in Parkinson's disease: A double‐blind placebo‐controlled trial
Auteurs : Christopher G. Goetz [États-Unis] ; Philippe Damier [France] ; Christine Hicking [Allemagne] ; Eugene Laska [États-Unis] ; Thomas Müller [Allemagne] ; C. Warren Olanow [États-Unis] ; Olivier Rascol [France] ; Hermann Russ [Allemagne]Source :
- Movement Disorders [ 0885-3185 ] ; 2007-01-15.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Adult, Antiparkinson Agents (administration & dosage), Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Clinical trial, Double-Blind Method, Drug Administration Schedule, Dyskinesia, Dyskinesias (drug therapy), Dyskinesias (etiology), Dyskinesias (physiopathology), Female, Humans, Male, Middle Aged, Nervous system diseases, Organic Chemicals (administration & dosage), Organic Chemicals (adverse effects), Organic Chemicals (therapeutic use), Parkinson Disease (complications), Parkinson Disease (physiopathology), Parkinson disease, Parkinson's disease, Placebo, Sarizotan, Serotonin Receptor Agonists (therapeutic use), Severity of Illness Index, Treatment, dyskinesias, randomized clinical trials, sarizotan.
- MESH :
- chemical , administration & dosage : Antiparkinson Agents, Organic Chemicals.
- chemical , adverse effects : Antiparkinson Agents, Organic Chemicals.
- chemical , therapeutic use : Antiparkinson Agents, Organic Chemicals, Serotonin Receptor Agonists.
- complications : Parkinson Disease.
- drug therapy : Dyskinesias.
- etiology : Dyskinesias.
- physiopathology : Dyskinesias, Parkinson Disease.
- Adult, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Severity of Illness Index.
Abstract
The objective of this study is to conduct a dose‐finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5‐HT1A agonist properties and additional high affinity for D3 and D4 receptors. An open label study documented improvements in PD patients with levodopa‐induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo‐controlled, double‐blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary‐based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention‐to‐treat population. No significant changes occurred on sarizotan compared to placebo on any diary‐based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan‐ and placebo‐treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome. © 2006 Movement Disorder Society
Url:
DOI: 10.1002/mds.21226
Affiliations:
- Allemagne, France, États-Unis
- District de Darmstadt, Hesse (Land), Illinois, Midi-Pyrénées, État de New York
- Darmstadt, Nantes, Toulouse
- Université Toulouse III - Paul Sabatier, Université de Toulouse
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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="2007-01-15">2007-01-15</date><biblScope unit="vol">22</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="179">179</biblScope><biblScope unit="page" to="186">186</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">0DE4A22F865B7A74E84AF35376BF9D26DF62324C</idno><idno type="DOI">10.1002/mds.21226</idno><idno type="ArticleID">MDS21226</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Antiparkinson Agents (administration & dosage)</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Clinical trial</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Dyskinesia</term><term>Dyskinesias (drug therapy)</term><term>Dyskinesias (etiology)</term><term>Dyskinesias (physiopathology)</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Nervous system diseases</term><term>Organic Chemicals (administration & dosage)</term><term>Organic Chemicals (adverse effects)</term><term>Organic Chemicals (therapeutic use)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (physiopathology)</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>Placebo</term><term>Sarizotan</term><term>Serotonin Receptor Agonists (therapeutic use)</term><term>Severity of Illness Index</term><term>Treatment</term><term>dyskinesias</term><term>randomized clinical trials</term><term>sarizotan</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiparkinson Agents</term><term>Organic Chemicals</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Organic Chemicals</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Organic Chemicals</term><term>Serotonin Receptor Agonists</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesias</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesias</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Dyskinesias</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Severity of Illness Index</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dyskinésie</term><term>Essai clinique</term><term>Parkinson maladie</term><term>Placebo</term><term>Sarizotan</term><term>Système nerveux pathologie</term><term>Traitement</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The objective of this study is to conduct a dose‐finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5‐HT1A agonist properties and additional high affinity for D3 and D4 receptors. An open label study documented improvements in PD patients with levodopa‐induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo‐controlled, double‐blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary‐based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention‐to‐treat population. No significant changes occurred on sarizotan compared to placebo on any diary‐based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan‐ and placebo‐treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome. © 2006 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>États-Unis</li></country><region><li>District de Darmstadt</li><li>Hesse (Land)</li><li>Illinois</li><li>Midi-Pyrénées</li><li>État de New York</li></region><settlement><li>Darmstadt</li><li>Nantes</li><li>Toulouse</li></settlement><orgName><li>Université Toulouse III - Paul Sabatier</li><li>Université de Toulouse</li></orgName></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name></region><name sortKey="Laska, Eugene" sort="Laska, Eugene" uniqKey="Laska E" first="Eugene" last="Laska">Eugene Laska</name><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C. Warren" last="Olanow">C. Warren Olanow</name></country><country name="France"><noRegion><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name></noRegion><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Hicking, Christine" sort="Hicking, Christine" uniqKey="Hicking C" first="Christine" last="Hicking">Christine Hicking</name></region><name sortKey="Muller, Thomas" sort="Muller, Thomas" uniqKey="Muller T" first="Thomas" last="Müller">Thomas Müller</name><name sortKey="Russ, Hermann" sort="Russ, Hermann" uniqKey="Russ H" first="Hermann" last="Russ">Hermann Russ</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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