Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.
Identifieur interne : 000B01 ( Ncbi/Checkpoint ); précédent : 000B00; suivant : 000B02Orodispersible 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
Affiliations:
- France
- Midi-Pyrénées, Occitanie (région administrative), Île-de-France
- Paris, Toulouse
- Hôpital de la Salpêtrière
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000B07
- to stream PubMed, to step Curation: 000A67
- to stream PubMed, to step Checkpoint: 000A67
- to stream Ncbi, to step Merge: 000B01
- to stream Ncbi, to step Curation: 000B01
Links to Exploration step
pubmed:20063435Le document en format XML
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<affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Pharmacology, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier, Toulouse, France. rascol@cict.fr</nlm:affiliation>
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<term>Cross-Over Studies</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Drug Administration Routes</term>
<term>France</term>
<term>Humans</term>
<term>Logistic Models</term>
<term>Parkinson Disease (drug therapy)</term>
<term>Piribedil (administration & dosage)</term>
<term>Proportional Hazards Models</term>
<term>Severity of Illness Index</term>
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<term>Apomorphine</term>
<term>Piribedil</term>
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<term>Cross-Over Studies</term>
<term>Dose-Response Relationship, Drug</term>
<term>Double-Blind Method</term>
<term>Drug Administration Routes</term>
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<term>Logistic Models</term>
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<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>
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<tree><noCountry><name sortKey="Azulay, Jean Philippe" sort="Azulay, Jean Philippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name>
<name sortKey="Blin, Olivier" sort="Blin, Olivier" uniqKey="Blin O" first="Olivier" last="Blin">Olivier Blin</name>
<name sortKey="Bonnet, Anne Marie" sort="Bonnet, Anne Marie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name>
<name sortKey="Brefel Courbon, Christine" sort="Brefel Courbon, Christine" uniqKey="Brefel Courbon C" first="Christine" last="Brefel-Courbon">Christine Brefel-Courbon</name>
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<name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name>
<name sortKey="Debilly, Berengere" sort="Debilly, Berengere" uniqKey="Debilly B" first="Bérengère" last="Debilly">Bérengère Debilly</name>
<name sortKey="Durif, Frank" sort="Durif, Frank" uniqKey="Durif F" first="Frank" last="Durif">Frank Durif</name>
<name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name>
<name sortKey="Grouin, Jean Marie" sort="Grouin, Jean Marie" uniqKey="Grouin J" first="Jean-Marie" last="Grouin">Jean-Marie Grouin</name>
<name sortKey="Pennaforte, Sylvie" sort="Pennaforte, Sylvie" uniqKey="Pennaforte S" first="Sylvie" last="Pennaforte">Sylvie Pennaforte</name>
<name sortKey="Villafane, Gabriel" sort="Villafane, Gabriel" uniqKey="Villafane G" first="Gabriel" last="Villafane">Gabriel Villafane</name>
<name sortKey="Yaici, Sadek" sort="Yaici, Sadek" uniqKey="Yaici S" first="Sadek" last="Yaici">Sadek Yaici</name>
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<country name="France"><region name="Occitanie (région administrative)"><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name>
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<name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
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