Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson's disease.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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: Nobutaka Hattori, Masashi Kikuchi, Noriaki Adachi, David Hewitt, Susan Huyck, Tadayuki Saito
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 32 Pg. 73-79 (11 2016) ISSN: 1873-5126 [Electronic] England
• PMID: 27632893 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Pyrimidines
• Triazoles
• 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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiparkinson Agents (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Japan
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Pyrimidines (therapeutic use)
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Triazoles (therapeutic use)