Efficacy and safety of adjunctive lacosamide for the treatment of partial-onset seizures in Chinese and Japanese adults: A randomized, double-blind, placebo-controlled study.
To evaluate the efficacy and safety of adjunctive lacosamide treatment in Chinese and Japanese adults with uncontrolled focal (partial-onset) seizures (POS), with or without secondary generalization.



A 24-week, randomized, double-blind, placebo-controlled study (EP0008; NCT01710657) was conducted in patients (aged 16-70 years) with uncontrolled POS and taking 1-3 concomitant antiepileptic drugs from 72 sites across China and Japan. Following an 8-week Baseline period, randomized patients received lacosamide 200mg/day (100mg twice daily), 400mg/day (200mg twice daily), or placebo for 4-week Titration and 12-week Maintenance periods. The primary efficacy variable was the change in POS frequency per 28days from Baseline to Maintenance.



Overall, 692 patients were screened; 548 were randomized to placebo (n=184), lacosamide 200mg/day (n=183), or lacosamide 400mg/day (n=181); 485 (88.5%) completed the study. The median change (range) in POS frequency per 28days from Baseline to Maintenance was -3.33 (-754.3 to 165.2), -4.50 (-97.5 to 28.2), and -1.22 (-93.0 to 39.8) in the lacosamide 200mg/day, 400mg/day, and placebo groups, respectively. Significant percentage reductions in POS frequency over placebo per 28days from Baseline to Maintenance were observed for lacosamide 200mg/day (29.4% [95% CI 18.7-38.7%], p<0.001) and 400mg/day (39.6% [30.5-47.6%], p<0.001). Higher ≥50% and ≥75% responder and seizure freedom rates were observed in lacosamide-treated patients vs placebo. Treatment-emergent adverse events reported by ≥10% of all lacosamide-treated patients occurring at ≥2% difference compared with placebo were dizziness (25.9% vs 9.2%) and somnolence (10.2% vs 3.8%). Dose-proportional pharmacokinetics were consistent with earlier global pivotal trials.



Adjunctive lacosamide (200 and 400mg/day) was efficacious in reducing POS frequency in Chinese and Japanese patients with a safety and tolerability profile consistent with the three global pivotal studies.
Huashan Hospital Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. Electronic address: profzhong@sina.com.
Zhen
Z
Hong
NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 86, Aoi-ku, Shizuoka 420-8688, Japan. Electronic address: yshinoue@gmail.com.
Yushi
Y
Inoue
The Second Affiliated Hospital of Guangzhou Medical University, Changgang Dong Road 250#, Guangdong 510260, China. Electronic address: wpliao@163.net.
Weiping
W
Liao
The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: hongmeiyp@126.com.
Hongmei
H
Meng
The First Affiliated Hospital of Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China. Electronic address: xfyp@163.com.
Xuefeng
X
Wang
The First Affiliated Hospital of Kunming Medical University, 295 Xichang Lu, Kunming 650032, Yunnan, China. Electronic address: wmw85@hotmail.com.
Wenmin
W
Wang
The First Affiliated Hospital of Sun Yat-sen University, 1 Zhongshan 2nd Road, Yuexiu, Guangzhou 510000, Guangdong, China. Electronic address: lmzhou56@163.com.
Liemin
L
Zhou
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address: zfx001@yahoo.com.
Liming
L
Zhang
UCB Pharma, Shanghai, China. Electronic address: Xinlu.Du@ucb.com.
Xinlu
X
Du
UCB Pharma, Monheim am Rhein, Germany. Electronic address: Frank.Tennigkeit@ucb.com.
Frank
F
Tennigkeit
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002681:China; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
Antiepileptic drugs; Epilepsy; Focal seizure; Lacosamide; Tolerability