Pregabalin add-on therapy using a flexible, optimized dose schedule in refractory partial epilepsies: a double-blind, randomized, placebo-controlled, multicenter trial.
OBJECTIVE
To evaluate the efficacy and safety of pregabalin (PGB) as adjunctive therapy, using a flexible-dosing schedule in Korean patients with refractory partial-onset seizures.


METHODS
This randomized, double-blind (DB), placebo-controlled trial consists of a 6-week baseline, a 12-week DB treatment, and a 1-week taper phase. Patients having recurrent partial seizures (>or=4 seizures during baseline phase) under adequate pharmacotherapy were recruited to be randomized to PGB or placebo (PLC) in a 2 to 1 ratio. Starting dose was 150 mg/day, increased every 2 weeks by 150-mg/day increments up to maximum dose of 600 mg/day. The primary efficacy parameter was response ratio (RRatio) for all partial seizures.


RESULTS
A total of 178 patients (119 in PGB, 59 in PLC) were assigned to the study. Median daily doses of PGB and PLC were 367 and 420 mg/day, respectively. RRatio least squares (LS) mean was -35.8 in the PGB group and -23.2 in the PLC group, with estimated difference in RRatios being -12.6 [95% confidence interval (CI): -22.7 to -2.5, p = 0.015] in the intent-to-treat (ITT) population. Analysis of secondary efficacy measures showed a general trend favoring PGB over PLC. Seventy-seven patients (64.7%) in the PGB group and 18 patients (30.5%) in the PLC group developed adverse events (AEs) related to the study drug. Seven patients (5.9%) in the PGB group discontinued the study prematurely because of AEs. In the post hoc analysis, a significant weight gain (>or=7% of baseline body weight) was found in 24.8% of patients taking PGB, which was more frequent in patients with a lower body mass index (BMI <or=20).


CONCLUSIONS
PGB was effective and easily tolerable as add-on treatment in an Asian population with refractory partial-onset seizures.
Lee
Byung In
BI
Department of Neurology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea. bilee@yuhs.ac
Yi
Sangdoe
S
Hong
Seung Bong
SB
Kim
Myeong-Kyu
MK
Lee
Sang Ahm
SA
Lee
Sang Kun
SK
Shin
Dong-Jin
DJ
Kim
Jae Moon
JM
Song
Hong Ki
HK
Heo
Kyoung
K
Lowe
Wing
W
Leon
Teresa
T
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D000069583:Pregabalin; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid