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Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.
Mov Disord. 2010 Feb 15; 25(3):368-76.MD

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.

Authors+Show Affiliations

Department of Clinical Pharmacology, INSERM Clinical Investigation Center CIC-9302 and UMR-825, CHU Toulouse-Purpan and University Paul Sabatier, Toulouse, France. rascol@cict.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20063435

Citation

Rascol, Olivier, et al. "Orodispersible Sublingual Piribedil to Abort OFF Episodes: a Single Dose Placebo-controlled, Randomized, Double-blind, Cross-over Study." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 25, no. 3, 2010, pp. 368-76.
Rascol O, Azulay JP, Blin O, et al. Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study. Mov Disord. 2010;25(3):368-76.
Rascol, O., Azulay, J. P., Blin, O., Bonnet, A. M., Brefel-Courbon, C., Césaro, P., Damier, P., Debilly, B., Durif, F., Galitzky, M., Grouin, J. M., Pennaforte, S., Villafane, G., Yaici, S., & Agid, Y. (2010). Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study. Movement Disorders : Official Journal of the Movement Disorder Society, 25(3), 368-76. https://doi.org/10.1002/mds.22922
Rascol O, et al. Orodispersible Sublingual Piribedil to Abort OFF Episodes: a Single Dose Placebo-controlled, Randomized, Double-blind, Cross-over Study. Mov Disord. 2010 Feb 15;25(3):368-76. PubMed PMID: 20063435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study. AU - Rascol,Olivier, AU - Azulay,Jean-Philippe, AU - Blin,Olivier, AU - Bonnet,Anne-Marie, AU - Brefel-Courbon,Christine, AU - Césaro,Pierre, AU - Damier,Philippe, AU - Debilly,Bérengère, AU - Durif,Frank, AU - Galitzky,Monique, AU - Grouin,Jean-Marie, AU - Pennaforte,Sylvie, AU - Villafane,Gabriel, AU - Yaici,Sadek, AU - Agid,Yves, PY - 2010/1/12/entrez PY - 2010/1/12/pubmed PY - 2010/6/3/medline SP - 368 EP - 76 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 25 IS - 3 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/20063435/Orodispersible_sublingual_piribedil_to_abort_OFF_episodes:_a_single_dose_placebo_controlled_randomized_double_blind_cross_over_study_ L2 - https://doi.org/10.1002/mds.22922 DB - PRIME DP - Unbound Medicine ER -