Zhen Hong1, Yushi Inoue2, Weiping Liao3, Hongmei Meng4, Xuefeng Wang5, Wenmin Wang6, Liemin Zhou7, Liming Zhang8, Xinlu Du9, Frank Tennigkeit10. 1. Huashan Hospital Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. Electronic address: profzhong@sina.com. 2. NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 86, Aoi-ku, Shizuoka 420-8688, Japan. Electronic address: yshinoue@gmail.com. 3. The Second Affiliated Hospital of Guangzhou Medical University, Changgang Dong Road 250#, Guangdong 510260, China. Electronic address: wpliao@163.net. 4. The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: hongmeiyp@126.com. 5. The First Affiliated Hospital of Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China. Electronic address: xfyp@163.com. 6. The First Affiliated Hospital of Kunming Medical University, 295 Xichang Lu, Kunming 650032, Yunnan, China. Electronic address: wmw85@hotmail.com. 7. The First Affiliated Hospital of Sun Yat-sen University, 1 Zhongshan 2nd Road, Yuexiu, Guangzhou 510000, Guangdong, China. Electronic address: lmzhou56@163.com. 8. The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address: zfx001@yahoo.com. 9. UCB Pharma, Shanghai, China. Electronic address: Xinlu.Du@ucb.com. 10. UCB Pharma, Monheim am Rhein, Germany. Electronic address: Frank.Tennigkeit@ucb.com.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
RCT Entities:
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Viktor Farkas; Barbara Steinborn; J Robert Flamini; Ying Zhang; Nancy Yuen; Simon Borghs; Ali Bozorg; Tony Daniels; Paul Martin; Hannah C Carney; Svetlana Dimova; Ingrid E Scheffer Journal: Neurology Date: 2019-08-28 Impact factor: 9.910