Premium
Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study
Author(s) -
Rascol Olivier,
Azulay JeanPhilippe,
Blin Olivier,
Bonnet AnneMarie,
BrefelCourbon Christine,
Césaro Pierre,
Damier Philippe,
Debilly Bérengère,
Durif Frank,
Galitzky Monique,
Grouin JeanMarie,
Pennaforte Sylvie,
Villafane Gabriel,
Yaici Sadek,
Agid Yves
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.22922
Subject(s) - placebo , medicine , apomorphine , anesthesia , adverse effect , clinical endpoint , levodopa , pharmacokinetics , confidence interval , randomized controlled trial , agonist , parkinson's disease , receptor , alternative medicine , disease , pathology
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 × 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 (ΔUPDRS 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 wassuperior to placebo on ΔUPDRS 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, ΔUPDRS 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. © 2009 Movement Disorder Society