title: Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson's disease.
abstract: Preladenant, an adenosine 2A antagonist, reduced daily OFF time when administered as adjunctive treatment in a previous phase 2 trial in non-Japanese Parkinson's disease (PD) patients on stable doses of levodopa. This study aimed to evaluate preladenant as adjunctive therapy in Japanese patients with PD.
  
  
  
  In this randomized, placebo-controlled, double-blind, 12-week, dose-ranging, phase 2 study, Japanese patients with moderate to severe PD on a stable regimen of levodopa were randomly assigned 1:1:1:1 to preladenant 2 mg, 5 mg, or 10 mg BID or placebo. The primary efficacy end point was change from baseline to week 12 in mean OFF time, recorded using a PD diary. Safety and tolerability were also assessed.
  
  
  
  In total, 111 patients were randomly assigned to receive preladenant 2 mg, and 113 each received preladenant 5 mg, 10 mg, or placebo. In contrast to previous data, preladenant in this study did not demonstrate statistically significant efficacy; the primary outcome was -0.7 h (P = 0.0564), -0.5 h (P = 0.1844), and -0.3 h (P = 0.3386), respectively, for preladenant 2 mg, 5 mg, and 10 mg BID versus placebo. Overall, preladenant was well tolerated, and the frequency of adverse events appeared to be dose related.
  
  
  
  In this phase 2 study, preladenant used as adjunctive therapy in PD patients on stable doses of levodopa did not reduce mean OFF time; treatment was well tolerated at doses between 2 and 10 mg BID.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Adachi
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hewitt
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Huyck
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000978:Antiparkinson Agents; D011743:Pyrimidines; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine
keywords: Adjunctive therapy; Japan; Movement disorder; Parkinson's disease; Preladenant