Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.
Identifieur interne : 002972 ( Ncbi/Curation ); précédent : 002971; suivant : 002973Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.
Auteurs : Olivier Rascol [France] ; 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 Agid [France]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2010.
Descripteurs français
- Wicri :
- geographic : France.
English descriptors
- KwdEn :
- Administration, Sublingual, Antiparkinson Agents (administration & dosage), Apomorphine (administration & dosage), Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Routes, France, Humans, Logistic Models, Parkinson Disease (drug therapy), Piribedil (administration & dosage), Proportional Hazards Models, Severity of Illness Index.
- MESH :
- chemical , administration & dosage : Antiparkinson Agents, Apomorphine, Piribedil.
- geographic : France.
- drug therapy : Parkinson Disease.
- Administration, Sublingual, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Routes, Humans, Logistic Models, Proportional Hazards Models, Severity of Illness Index.
Abstract
S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) 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 x 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 (Delta UPDRS 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 Delta UPDRS 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, Delta UPDRS 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.
DOI: 10.1002/mds.22922
PubMed: 20063435
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pubmed:20063435Le document en format XML
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xml:lang="en"><term>Antiparkinson Agents</term><term>Apomorphine</term><term>Piribedil</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>France</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Sublingual</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Administration Routes</term><term>Humans</term><term>Logistic Models</term><term>Proportional Hazards Models</term><term>Severity of Illness Index</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>France</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) 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 x 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 (Delta UPDRS 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 Delta UPDRS 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, Delta UPDRS 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></record>Pour manipuler ce document sous Unix (Dilib)
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