Abstract：
Lasmiditan is the first 5-HT1F receptor agonist with potential to address the huge unmet medical needs for the treatment of migraine in China. The CENTURION study was the first phase 3 study of lasmiditan in Caucasian and Chinese patients with migraine. This post hoc analysis further demonstrates the safety profile of lasmiditan in the Chinese population and was urgently needed.
Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed.
A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy.
In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population.
NCT03670810.
Although there is significant unmet medical need among patients with migraine, there has been no novel compound for treatment of migraine over past two decades in China. These unmet medical needs persist because the current available medications for the acute treatment of migraine are reported to have safety and tolerability issues. Lasmiditan is a new class of acute migraine medication (5-HT receptor agonist with high selectivity for the 5-HT1F receptor) with a proven efficacy and safety in phase 2 and 3 studies. Owing to some differences in clinical practice between China and western countries, there is need to get additional evidence on safety of lasmiditan in the Chinese population to support its usage in clinical practice.This post hoc analysis was conducted to present the detailed safety profile of lasmiditan in the Chinese population using data from the CENTURION study. Approximately half of the analyzed population was not covered in the published primary cohort.The results show that in the Chinese population of the study, most of the treatment-emergent adverse events (TEAEs) were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort with no new safety concerns observed in the Chinese population. The overall safety profile of lasmiditan in the Chinese population was generally consistent with the primary cohort. The results provide additional evidence and emphasize that lasmiditan may be considered as a useful acute treatment option with acceptable safety profile for patients with migraine in China.
Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed.
A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy.
In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population.
NCT03670810.
Although there is significant unmet medical need among patients with migraine, there has been no novel compound for treatment of migraine over past two decades in China. These unmet medical needs persist because the current available medications for the acute treatment of migraine are reported to have safety and tolerability issues. Lasmiditan is a new class of acute migraine medication (5-HT receptor agonist with high selectivity for the 5-HT1F receptor) with a proven efficacy and safety in phase 2 and 3 studies. Owing to some differences in clinical practice between China and western countries, there is need to get additional evidence on safety of lasmiditan in the Chinese population to support its usage in clinical practice.This post hoc analysis was conducted to present the detailed safety profile of lasmiditan in the Chinese population using data from the CENTURION study. Approximately half of the analyzed population was not covered in the published primary cohort.The results show that in the Chinese population of the study, most of the treatment-emergent adverse events (TEAEs) were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort with no new safety concerns observed in the Chinese population. The overall safety profile of lasmiditan in the Chinese population was generally consistent with the primary cohort. The results provide additional evidence and emphasize that lasmiditan may be considered as a useful acute treatment option with acceptable safety profile for patients with migraine in China.
摘要：
Lasmiditan是第一种5-HT1F受体激动剂，有潜力解决中国治疗偏头痛的巨大未满足的医疗需求。CENTURION研究是lasmiditan在高加索和中国偏头痛患者中的第一个3期研究。此事后分析进一步证明了lasmiditan在中国人群中的安全性，这是迫切需要的。
患者被随机分为1:1:1至lasmiditan200毫克lasmiditan100毫克，或对照组。因治疗引起的不良事件（TEAE）的发生率，其严重性,评估了经常报告的TEAE（≥5％）的治疗发作的发生率。持续时间,发病，并分析了疗效与非常常见的TEAE(≥10%)的关系。
本事后分析共纳入281名中国患者。没有报告死亡和研究药物相关治疗引起的严重不良事件（TESAE）。与安慰剂（26.6％）相比，接受lasmiditan200mg（73.9％）和100mg（66.3％）的患者中至少一种TEAE的发生率更高。TEAE的严重程度一般为轻度或中度，在第一次发作期间，经常报告的TEAE的发生率通常最高。非常常见的TEAE与lasmiditan包括头晕，虚弱,嗜睡,肌肉无力,疲劳,和恶心。在第一次发作期间，头晕的持续时间最长。无心脑血管缺血事件和5-羟色胺综合征。存在非常常见的TEAE（恶心除外），和严重的头晕,似乎对疗效没有负面影响。
在CENTURION研究的中国人口中，大多数TEAE是神经系统的，轻度或中度严重程度，和自我限制。首次发作时频繁报告的TEAE的分布与主要队列不同，而中国人群中lasmiditan的总体安全性与CENTURION主要队列基本一致.在中国人群中没有观察到新的安全问题。
NCT03670810。
虽然偏头痛患者存在大量未满足的医疗需求，在过去的二十年中，中国还没有新的治疗偏头痛的化合物。这些未满足的医疗需求持续存在，因为据报道，目前用于偏头痛急性治疗的药物具有安全性和耐受性问题。Lasmiditan是一类新型的急性偏头痛药物（5-HT受体激动剂，对5-HT1F受体具有高选择性），在2期和3期研究中具有良好的疗效和安全性。由于中国和西方国家在临床实践上的一些差异，有必要在中国人群中获得更多关于lasmiditan安全性的证据，以支持其在临床实践中的使用。使用来自CENTURION研究的数据，进行了此事后分析，以显示中国人群中lasmiditan的详细安全性。大约一半的分析人群未被纳入已发表的主要队列。研究结果表明,在中国人群中,大多数治疗引起的不良事件（TEAE）是神经系统，轻度或中度严重程度，和自我限制。首次发作时频繁报告的TEAE的分布与主要队列不同，在中国人群中未观察到新的安全性问题。Lasmiditan在中国人群中的总体安全性与主要队列基本一致。结果提供了更多的证据，并强调lasmiditan可能被认为是一种有用的急性治疗选择，对中国的偏头痛患者具有可接受的安全性。
患者被随机分为1:1:1至lasmiditan200毫克lasmiditan100毫克，或对照组。因治疗引起的不良事件（TEAE）的发生率，其严重性,评估了经常报告的TEAE（≥5％）的治疗发作的发生率。持续时间,发病，并分析了疗效与非常常见的TEAE(≥10%)的关系。
本事后分析共纳入281名中国患者。没有报告死亡和研究药物相关治疗引起的严重不良事件（TESAE）。与安慰剂（26.6％）相比，接受lasmiditan200mg（73.9％）和100mg（66.3％）的患者中至少一种TEAE的发生率更高。TEAE的严重程度一般为轻度或中度，在第一次发作期间，经常报告的TEAE的发生率通常最高。非常常见的TEAE与lasmiditan包括头晕，虚弱,嗜睡,肌肉无力,疲劳,和恶心。在第一次发作期间，头晕的持续时间最长。无心脑血管缺血事件和5-羟色胺综合征。存在非常常见的TEAE（恶心除外），和严重的头晕,似乎对疗效没有负面影响。
在CENTURION研究的中国人口中，大多数TEAE是神经系统的，轻度或中度严重程度，和自我限制。首次发作时频繁报告的TEAE的分布与主要队列不同，而中国人群中lasmiditan的总体安全性与CENTURION主要队列基本一致.在中国人群中没有观察到新的安全问题。
NCT03670810。
虽然偏头痛患者存在大量未满足的医疗需求，在过去的二十年中，中国还没有新的治疗偏头痛的化合物。这些未满足的医疗需求持续存在，因为据报道，目前用于偏头痛急性治疗的药物具有安全性和耐受性问题。Lasmiditan是一类新型的急性偏头痛药物（5-HT受体激动剂，对5-HT1F受体具有高选择性），在2期和3期研究中具有良好的疗效和安全性。由于中国和西方国家在临床实践上的一些差异，有必要在中国人群中获得更多关于lasmiditan安全性的证据，以支持其在临床实践中的使用。使用来自CENTURION研究的数据，进行了此事后分析，以显示中国人群中lasmiditan的详细安全性。大约一半的分析人群未被纳入已发表的主要队列。研究结果表明,在中国人群中,大多数治疗引起的不良事件（TEAE）是神经系统，轻度或中度严重程度，和自我限制。首次发作时频繁报告的TEAE的分布与主要队列不同，在中国人群中未观察到新的安全性问题。Lasmiditan在中国人群中的总体安全性与主要队列基本一致。结果提供了更多的证据，并强调lasmiditan可能被认为是一种有用的急性治疗选择，对中国的偏头痛患者具有可接受的安全性。
