Perampanel in Parkinson disease fluctuations: a double-blind randomized trial with placebo and entacapone.

Abstract

OBJECTIVES:

Perampanel is a selective and noncompetitive α-amino-3-hydroxy-5-methylisoxazole propionic acid-type glutamate receptor antagonist that improves motor symptoms in animal models of Parkinson disease (PD). The aim of this study was to assess the efficacy and tolerability of perampanel in L-dopa-treated patients with moderately severe PD and motor fluctuations using an active comparator study design.

METHODS:

This was a prospective, randomized, double-blind, 3-arm, parallel-group, controlled study assessing the effects of perampanel (4 mg/d), placebo, or entacapone (200 mg with each dose of L-dopa) in 723 L-dopa-treated patients with PD with "OFF" problems. The primary outcome measure was the change from baseline in mean total daily OFF time based on diaries. Secondary end points included change from baseline in Unified Parkinson's Disease Rating Scale part II while OFF, Unified Parkinson's Disease Rating Scale part III while "ON," and mean total daily ON time without dyskinesias or with nontroublesome dyskinesias.

RESULTS:

In total, 480 patients (66.4%) completed the study, which was terminated early after negative results of 2 other large placebo-controlled studies became available. Perampanel was not superior to placebo on any efficacy end point, whereas entacapone was superior to placebo on the primary end point (P = 0.034) and most secondary outcomes. Perampanel was generally well tolerated.

CONCLUSIONS:

Perampanel (4 mg/d) was well tolerated but did not have a clinically significant effect in improving motor symptoms of L-dopa-treated patients with moderately advanced PD and motor fluctuations. These patients did respond to the active comparator, entacapone, confirming the validity of the findings despite the early termination of the study.

• Authors: Olivier Rascol, Paolo Barone, Madhuri Behari, Murat Emre, Nir Giladi, C Warren Olanow, Evzen Ruzicka, Francesco Bibbiani, David Squillacote, Anna Patten, Eduardo Tolosa
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) 2012 Jan-Feb Vol. 35 Issue 1 Pg. 15-20 ISSN: 1537-162X [Electronic] United States
• PMID: 22222634 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antiparkinson Agents
• Catechols
• Enzyme Inhibitors
• Excitatory Amino Acid Antagonists
• Nitriles
• Pyridones
• Levodopa
• entacapone
• perampanel

Topics

• Aged
• Antiparkinson Agents (adverse effects)
• Catechols (therapeutic use)
• Double-Blind Method
• Dyskinesia, Drug-Induced (drug therapy, etiology)
• Enzyme Inhibitors (therapeutic use)
• Excitatory Amino Acid Antagonists (therapeutic use)
• Female
• Humans
• International Cooperation
• Levodopa (adverse effects)
• Male
• Middle Aged
• Nitriles (therapeutic use)
• Parkinson Disease (drug therapy)
• Prospective Studies
• Pyridones (therapeutic use)
• Severity of Illness Index
• Treatment Outcome