Ⅲ期临床试验非盲延期阶段联合使用吡仑帕奈的局灶性癫痫患者的四年药物安全性、耐受性及发作结局：307 号研究_Journal of Epilepsy

Authors：

 Gregory LKrauss , EmilioPerucca , PatrickKwan , 覃英杰　译 , 熊维希　慕洁　审

Corresponding author：

Gregory LKrauss, Email: gkrauss@jhmi.edu

Keywords：

抗癫痫药物; 局灶性痫性发作; 长期安全性及耐受性; 吡仑帕奈; 继发全面性痫性发作

DOI：

10.7507/2096-0247.20200012

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

评估 307 号研究（临床试验验证码：NCT00735397）Ⅲ期非盲延期阶段（OLEx）联合使用吡仑帕奈的局灶性癫痫患者的药物安全性、耐受性及痫性发作结局。患者在完成任一 III 期双盲试验后均可进入非盲延期阶段（Open-labelextension，OLEx）。对所有 OLEx 队列中有同样最小吡伦帕奈暴露剂量的局灶性癫痫和继发全面性癫痫（Secondarily generalized seizures，SGS）的患者进行药物安全性及耐受性和痫性发作结局（每 28 d 中位痫性发作减少率、反应率和无发作率）的分析。另外，针对 OLEx 的早期失访进行了额外的敏感性分析。从 1 480 例双盲试验中随机分组的患者共纳入 1 218 例。大部分患者（65.4%～80.9%）仅用吡仑帕奈 12 mg，每日一次，进行治疗，并在相同剂量下完成长期的检测，或是相对基线联合使用少量抗癫痫药物（AEDs）。长期的药物安全性及耐受性结果与双盲研究一致。导致超过 1% 的患者研究中断治疗的紧急不良反应事件（Treatment-emergent adverse events，TEAEs）包括眩晕、易激、疲劳。有临床意义的 TEAEs 稳定期为 4 年。所有队列中患者的痫性发作结局随时间持续改善。对于接受 3 年（n = 436）、4 年（n = 78）药物治疗的患者 28 d 中位痫性发作减少率分别为 62%、70.6%，相应的 50% 反应率为 59.6%、67.9%。最大 28 d 中位痫性发作减少率发生于基线水平的 SGS 患者，接受 3 年（n = 190）、4 年（n = 28）药物治疗分别为 88.0% 和 100.0%。在这些队列中分别有 40.0% 和 53.6% 的患者达到了无 SGS。排除早期失访后的 28 d 中位痫性发作减少率结果类似。长期吡仑帕奈联合用药（≤4 年）不会导致新的药物安全性及耐受性问题，并且可以很大程度地减少痫性发作，特别是基线水平的 SGS 患者。

Citation： Gregory LKrauss, EmilioPerucca, PatrickKwan, 覃英杰　译, 熊维希　慕洁　审. Ⅲ期临床试验非盲延期阶段联合使用吡仑帕奈的局灶性癫痫患者的四年药物安全性、耐受性及发作结局：307 号研究. Journal of Epilepsy, 2020, 6(1): 63-69. doi: 10.7507/2096-0247.20200012 Copy

1.	European Medicines Agency (EMA). Fycompa_ Annex I: Summary ofProductCharacteristics, April 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002434/WC500130815.pdf. Accessed February 06, 2017.
2.	Food and Drug Administration (FDA). Fycompa_ PrescribingInformation, July 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202834s012,208277s001lbl.pdf. Accessed February 06, 2017.
3.	Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phaseIII study 306: adjunctive perampanel for refractory partial-onsetseizures. Neurology, 2012, 78(2): 1408-1415.
4.	French JA, Krauss GL, Biton V, et al. Adjunctive perampanel forrefractory partial-onset seizures: randomized phase III study 304. Neurology, 2012, 78(3): 589-596.
5.	French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctiveperampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia, 2013, 54(5): 117-125.
6.	Krauss GL, Perucca E, Ben-Menachem E, et al. Long-term safetyof perampaneland seizure outcomes in refractory partial-onsetseizures and secondarily generalized seizures: Results from phaseIII extension study 307. Epilepsia, 2014, 55(1): 1058-1068.
7.	Krauss GL, Perucca E, Ben-Menachem E, et al. Perampanel, aselective, noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapyfor refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia, 2013, 54(2): 126-134.
8.	Bootsma HP, Ricker L, Hekster YA, et al. The impact of sideeffects on long-term retention in three new antiepileptic drugs. Seizure, 2009, 18(4): 327-331.
9.	Rosenfeld W, Fountain NB, Kaubrys G, et al. Safety and efficacyof adjunctive lacosamide among patients with partial-onset seizuresin a long-term open-labelextension trial of up to 8 years. Epilepsy Behav, 2014, 41: 164-170.
10.	Steinhoff BJ, Ben-Menachem E, Ryvlin P, et al. Efficacy andsafety of adjunctive perampanel for the treatment of refractorypartial seizures: a pooled analysis of threephase III studies. Epilepsia, 2013, 54(3): 1481-1489.
11.	Pina-Garza JE, Yang H, Williams B, et al. Effect of adjunctiveperampanel on growth and development in adolescents with inadequatelycontrolled partial seizures. Neurology, 2015, 84(P1): 252.
12.	Kim HD, Chi CS, Desudchit T, et al. Review of clinical studies ofperampanel in adolescent patients. Brain Behav, 2016, 6: e00505.
13.	Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: Preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
14.	Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioraladverse events in randomized clinical studies of thenoncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(2): 1252-1263.
15.	Chung S, Williams B, Dobrinsky C, et al. perampanel with concomitantlevetiracetam and topiramate: Post hoc analysis ofadverse events related to hostility and aggression. Epilepsy Behav, 2017, 75: 79-85.

1. European Medicines Agency (EMA). Fycompa_ Annex I: Summary ofProductCharacteristics, April 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002434/WC500130815.pdf. Accessed February 06, 2017.
2. Food and Drug Administration (FDA). Fycompa_ PrescribingInformation, July 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202834s012,208277s001lbl.pdf. Accessed February 06, 2017.
3. Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phaseIII study 306: adjunctive perampanel for refractory partial-onsetseizures. Neurology, 2012, 78(2): 1408-1415.
4. French JA, Krauss GL, Biton V, et al. Adjunctive perampanel forrefractory partial-onset seizures: randomized phase III study 304. Neurology, 2012, 78(3): 589-596.
5. French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctiveperampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia, 2013, 54(5): 117-125.
6. Krauss GL, Perucca E, Ben-Menachem E, et al. Long-term safetyof perampaneland seizure outcomes in refractory partial-onsetseizures and secondarily generalized seizures: Results from phaseIII extension study 307. Epilepsia, 2014, 55(1): 1058-1068.
7. Krauss GL, Perucca E, Ben-Menachem E, et al. Perampanel, aselective, noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapyfor refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia, 2013, 54(2): 126-134.
8. Bootsma HP, Ricker L, Hekster YA, et al. The impact of sideeffects on long-term retention in three new antiepileptic drugs. Seizure, 2009, 18(4): 327-331.
9. Rosenfeld W, Fountain NB, Kaubrys G, et al. Safety and efficacyof adjunctive lacosamide among patients with partial-onset seizuresin a long-term open-labelextension trial of up to 8 years. Epilepsy Behav, 2014, 41: 164-170.
10. Steinhoff BJ, Ben-Menachem E, Ryvlin P, et al. Efficacy andsafety of adjunctive perampanel for the treatment of refractorypartial seizures: a pooled analysis of threephase III studies. Epilepsia, 2013, 54(3): 1481-1489.
11. Pina-Garza JE, Yang H, Williams B, et al. Effect of adjunctiveperampanel on growth and development in adolescents with inadequatelycontrolled partial seizures. Neurology, 2015, 84(P1): 252.
12. Kim HD, Chi CS, Desudchit T, et al. Review of clinical studies ofperampanel in adolescent patients. Brain Behav, 2016, 6: e00505.
13. Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: Preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
14. Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioraladverse events in randomized clinical studies of thenoncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(2): 1252-1263.
15. Chung S, Williams B, Dobrinsky C, et al. perampanel with concomitantlevetiracetam and topiramate: Post hoc analysis ofadverse events related to hostility and aggression. Epilepsy Behav, 2017, 75: 79-85.

Previous Article
癫痫持续状态长期结局：一项关键评价
Next Article
Study on the expression of Cdc42、N-WASP、Arp2/3 in peripheral blood of patients with drug-resistant epilepsy

Journal of Epilepsy

Ⅲ期临床试验非盲延期阶段联合使用吡仑帕奈的局灶性癫痫患者的四年药物安全性、耐受性及发作结局：307 号研究

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content