Perampanel in Parkinson disease fluctuations:  a double-blind randomized trial with placebo and entacapone.
OBJECTIVE
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.
Institut National de la Santé et de la Recherche Médicale Clinical Investigation Center, Toulouse University Hospital and University of Toulouse, France. olivier.rascol@univ-tlse3.fr
Olivier
O
Rascol
Paolo
P
Barone
Madhuri
M
Behari
Murat
M
Emre
Nir
N
Giladi
C Warren
CW
Olanow
Evzen
E
Ruzicka
Francesco
F
Bibbiani
David
D
Squillacote
Anna
A
Patten
Eduardo
E
Tolosa
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects; D002396:Catechols / Q000627:therapeutic use*; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007391:International Cooperation; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy; D011446:Prospective Studies; D011728:Pyridones / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009570:Nitriles; D011728:Pyridones; D007980:Levodopa; C071192:entacapone; C551441:perampanel