Abstract：
OBJECTIVE: In this post hoc analysis of a subset of patients from a long-term, open-label phase 3 study, we assessed ≥50%, ≥75%, ≥90%, and 100% seizure reduction and sustainability of these responses with cenobamate using a time-to-event analytical approach.
METHODS: Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12-week titration phase and received ≥1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (≥50%, ≥75%, ≥90%, or 100%), sustainability of that response was measured using a time-to-event methodology. An event was defined as the occurrence of a study visit at which the seizure frequency during the interval since the prior study visit exceeded the initially attained reduction level. Study visits during the maintenance phase occurred at 3-month intervals.
RESULTS: Of the 214 patients analyzed, 188 (88%), 177 (83%), 160 (75%), and 145 (68%) met ≥50%, ≥75%, ≥90%, and 100% seizure-reduction responses, respectively, for at least one study visit interval during the maintenance phase. The median (95% confidence interval [CI]) time to first visit without a ≥50% seizure reduction was not reached by 30 months of follow-up (53% of patients maintained their initial ≥50% seizure reduction). Median (95% CI) time to first visit without sustaining the initial ≥75%, ≥90%, or 100% seizure reduction was 13.0 (7.5-21.9) months, 7.5 (5.4-11.6) months, and 7.0 (5.3-10.4) months, respectively. Among the 145 patients who had 100% seizure reduction during at least one study visit, 22% remained seizure-free for at least 30 months and 63% had ≤3 study visits with seizures.
CONCLUSIONS: Adjunctive treatment with cenobamate led to sustained seizure reductions during the maintenance phase of the phase 3 safety study.
METHODS: Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12-week titration phase and received ≥1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (≥50%, ≥75%, ≥90%, or 100%), sustainability of that response was measured using a time-to-event methodology. An event was defined as the occurrence of a study visit at which the seizure frequency during the interval since the prior study visit exceeded the initially attained reduction level. Study visits during the maintenance phase occurred at 3-month intervals.
RESULTS: Of the 214 patients analyzed, 188 (88%), 177 (83%), 160 (75%), and 145 (68%) met ≥50%, ≥75%, ≥90%, and 100% seizure-reduction responses, respectively, for at least one study visit interval during the maintenance phase. The median (95% confidence interval [CI]) time to first visit without a ≥50% seizure reduction was not reached by 30 months of follow-up (53% of patients maintained their initial ≥50% seizure reduction). Median (95% CI) time to first visit without sustaining the initial ≥75%, ≥90%, or 100% seizure reduction was 13.0 (7.5-21.9) months, 7.5 (5.4-11.6) months, and 7.0 (5.3-10.4) months, respectively. Among the 145 patients who had 100% seizure reduction during at least one study visit, 22% remained seizure-free for at least 30 months and 63% had ≤3 study visits with seizures.
CONCLUSIONS: Adjunctive treatment with cenobamate led to sustained seizure reductions during the maintenance phase of the phase 3 safety study.
摘要：
目的：在对长期患者子集的事后分析中，开放标签阶段3研究，我们评估≥50%，≥75%,≥90%,和100％的癫痫发作减少和这些反应的可持续性与使用时间事件分析方法的西诺本。
方法：240例未控制的局灶性癫痫发作患者有足够的癫痫发作数据，214人完成了12周的滴定阶段，并在维持阶段（最大剂量为400mg/天）接受了≥1剂的西诺本，并包括在此事后分析中。在满足初始给定癫痫发作减少水平(≥50%，≥75%,≥90%,或100%)，该反应的可持续性是使用事件发生时间方法来衡量的。事件定义为研究访视的发生,其中自先前研究访视以来的间隔期间的癫痫发作频率超过最初达到的减少水平。在维持阶段的研究访问以3个月的间隔进行。
结果：在分析的214例患者中，188（88%），177（83%），160（75%），145（68%）满足≥50%，≥75%,≥90%,100%的癫痫发作减少反应，分别,在维持阶段至少有一次研究访问间隔。在30个月的随访中，没有达到癫痫发作减少≥50％的首次就诊的中位时间（95％CI）（53％的患者维持其最初的癫痫发作减少≥50％）。在不维持初始≥75%的情况下，首次就诊的中位数（95%CI）时间，≥90%,或100%癫痫发作减少13.0(7.5-21.9)个月，7.5（5.4-11.6）个月，和7.0(5.3-10.4)个月，分别。在至少一次研究访视期间癫痫发作减少100％的145名患者中，22％的人至少30个月没有癫痫发作，63%的患者有≤3次癫痫发作的研究访视。
结论：在3期安全性研究的维持阶段，西诺比特辅助治疗导致癫痫持续减少。
方法：240例未控制的局灶性癫痫发作患者有足够的癫痫发作数据，214人完成了12周的滴定阶段，并在维持阶段（最大剂量为400mg/天）接受了≥1剂的西诺本，并包括在此事后分析中。在满足初始给定癫痫发作减少水平(≥50%，≥75%,≥90%,或100%)，该反应的可持续性是使用事件发生时间方法来衡量的。事件定义为研究访视的发生,其中自先前研究访视以来的间隔期间的癫痫发作频率超过最初达到的减少水平。在维持阶段的研究访问以3个月的间隔进行。
结果：在分析的214例患者中，188（88%），177（83%），160（75%），145（68%）满足≥50%，≥75%,≥90%,100%的癫痫发作减少反应，分别,在维持阶段至少有一次研究访问间隔。在30个月的随访中，没有达到癫痫发作减少≥50％的首次就诊的中位时间（95％CI）（53％的患者维持其最初的癫痫发作减少≥50％）。在不维持初始≥75%的情况下，首次就诊的中位数（95%CI）时间，≥90%,或100%癫痫发作减少13.0(7.5-21.9)个月，7.5（5.4-11.6）个月，和7.0(5.3-10.4)个月，分别。在至少一次研究访视期间癫痫发作减少100％的145名患者中，22％的人至少30个月没有癫痫发作，63%的患者有≤3次癫痫发作的研究访视。
结论：在3期安全性研究的维持阶段，西诺比特辅助治疗导致癫痫持续减少。
