title: Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.
abstract: Piribedil is a D2 dopamine agonist, which has been shown to improve symptoms of Parkinson's disease (PD) when combined with L-dopa. The objective of this study was to compare the efficacy of piribedil monotherapy to placebo in patients with early PD over a 7-month period. Four hundred and five early PD patients were randomized (double-blind) to piribedil (150-300 mg/day) or placebo. L-dopa open-label supplementation was permitted. Unified Parkinson Disease Rating Scale part III (UPDRS III) score as the last observation on monotherapy over 7 months was the primary outcome measure. Secondary outcomes were proportion of responders (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months, UPDRS III subscores, and UPDRS II. UPDRS III improved on piribedil (-4.9 points) versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% CI = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher for piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P < 0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II improved on piribedil by -1.2 points, while it deteriorated by 1.5 points on placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion of patients remaining on monotherapy after 7 months was greater in the piribedil group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that reported for other dopamine agonists, gastrointestinal side effects being the most common (22% of patients in piribedil group vs. 14% on placebo). Piribedil is effective and safe as early PD therapy.
authors.affiliation: INSERM U455, Clinical Investigation Center and Departments of Clinical Pharmacology and Neurosciences, Faculté de Médecine, Toulouse, France. rascol@cict.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Alexandre Castro
authors.initials: AC
authors.lastname: Caldas
authors.forename: Stephen
authors.initials: S
authors.lastname: Senn
authors.forename: Susanna
authors.initials: S
authors.lastname: Del Signore
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy*; D010891:Piribedil / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D010891:Piribedil