PDF(Pubmed)
Abstract：
BACKGROUND: Lasmiditan (LTN) is a selective 5-HT1F receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).
METHODS: Patients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses.
RESULTS: Overall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks. The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks. Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.
CONCLUSIONS: In this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.
BACKGROUND: NCT03670810.
METHODS: Patients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses.
RESULTS: Overall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks. The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks. Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.
CONCLUSIONS: In this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.
BACKGROUND: NCT03670810.
摘要：
背景：Lasmiditan（LTN）是一种用于成人偏头痛急性治疗的选择性5-HT1F受体激动剂。我们提供了来自安慰剂对照的详细安全性发现，双盲3期研究,LTN治疗4次发作(CENTURION)。
方法：患者被随机分为1：1：1，以LTN200mg（LTN200），LTN100，或对照组，接受安慰剂3次发作，接受LTN50第3次或第4次发作（1：1）。对服用≥1剂量研究药物的患者进行安全性分析，在某些情况下,那些服用了所有4剂的人。
结果：总体而言，1471名患者治疗4494次发作。治疗引起的严重不良事件（SAE）的发生率为-安慰剂，n=2（0.4％）；LTN100，n=1（0.2％）；LTN200，n=2（0.4％）；在一名以上的患者中没有报告特异性治疗引起的SAE。Lasmiditan最常见的治疗紧急不良事件（TEAE）是头晕，感觉异常,疲劳,恶心,眩晕,和嗜睡；绝大多数是轻度或中度的。这些TEAE的发生率在第一次发作期间最高，在随后的发作期间下降。对于第一次发作时出现常见TEAE的患者，不到45％的人在随后的攻击中经历了相同的事件。在第一次发作中没有经历事件的患者在随后的发作中很少经历相同的事件。常见TEAE的发作时间为〜40分钟至1小时（取决于TEAE），对于个人TEAE，在不同的攻击中，发作是相似的。持续时间取决于TEAE和发作。感觉异常最短（所有发作<2小时）；其他常见TEAE的范围为1.8至5.5小时，在所有发作之间通常相似。据报道，LTN给药后有2例患者出现5-羟色胺综合征；治疗组之间的自杀率没有明显差异；没有证据表明机动车事故增加。
结论：在这个盲目的，控制,多次攻击研究,LTN通常与轻度或中度短期中枢神经系统相关的TEAE相关。TEAE在4次攻击中的频率趋于降低。
背景：NCT03670810。
方法：患者被随机分为1：1：1，以LTN200mg（LTN200），LTN100，或对照组，接受安慰剂3次发作，接受LTN50第3次或第4次发作（1：1）。对服用≥1剂量研究药物的患者进行安全性分析，在某些情况下,那些服用了所有4剂的人。
结果：总体而言，1471名患者治疗4494次发作。治疗引起的严重不良事件（SAE）的发生率为-安慰剂，n=2（0.4％）；LTN100，n=1（0.2％）；LTN200，n=2（0.4％）；在一名以上的患者中没有报告特异性治疗引起的SAE。Lasmiditan最常见的治疗紧急不良事件（TEAE）是头晕，感觉异常,疲劳,恶心,眩晕,和嗜睡；绝大多数是轻度或中度的。这些TEAE的发生率在第一次发作期间最高，在随后的发作期间下降。对于第一次发作时出现常见TEAE的患者，不到45％的人在随后的攻击中经历了相同的事件。在第一次发作中没有经历事件的患者在随后的发作中很少经历相同的事件。常见TEAE的发作时间为〜40分钟至1小时（取决于TEAE），对于个人TEAE，在不同的攻击中，发作是相似的。持续时间取决于TEAE和发作。感觉异常最短（所有发作<2小时）；其他常见TEAE的范围为1.8至5.5小时，在所有发作之间通常相似。据报道，LTN给药后有2例患者出现5-羟色胺综合征；治疗组之间的自杀率没有明显差异；没有证据表明机动车事故增加。
结论：在这个盲目的，控制,多次攻击研究,LTN通常与轻度或中度短期中枢神经系统相关的TEAE相关。TEAE在4次攻击中的频率趋于降低。
背景：NCT03670810。
