A Placebo-Controlled Dose-Finding Study of JNS019 (Topiramate) in Migraine Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 387
- 主要终点
- Mean Change From Baseline in Monthly Migraine Attacks (According to 24-Hour Rule) Through Month 6
研究概览
简要总结
The purpose of this study is to determine a recommended dose of topiramate in participants with migraine (type of severe headache that occurs periodically and is often associated with nausea, vomiting, and constipation or diarrhea), to verify the superiority (statistically more effective) of the drug to placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), and to assess if a same therapeutic effect can be observed between this study and overseas Caucasian clinical studies.
详细描述
This study is a multicenter (more than 1 site), placebo-controlled (compared to placebo), randomized (participants assigned study drug by chance), double-blind (neither the participant nor the physician know the assigned study drug), parallel-group comparison (comparison for each group at the same time) study. The study period consists of 4 phases: the observation phase, double-blind phase, exit period and follow-up period. After the double-blind phase, the participants will be transferred to the continuous treatment study. The observation phase which is started after informed consent consists of the washout period (non-treatment period with migraine preventive medication: at least 2 weeks) and baseline determination period (at least 4 weeks). The participants who complete the observation phase and meet the inclusion criteria will be randomly assigned to the topiramate 50 milligram (mg) group, topiramate 100-mg group or placebo group after registration. The double-blind phase consists of the titration period (dose-escalation, 4 weeks) and fixed-dose period (18 weeks). In the titration period, starting from 1 topiramate 25-mg tablet or 1 topiramate 25-mg placebo tablet once daily (1 tablet in the evening), the dose will be increased by 1 tablet every week up to twice daily (2 tablets in the morning, 2 tablets in the evening). After that, the twice-daily treatment (2 tablets in the morning, 2 tablets in the evening) will be continued for 7 days from Day 22 to Day 28. In the fixed-dose period, the topiramate 25-mg tablets or topiramate 25-mg placebo tablets at the same dose as that in the final treatment in titration period will be continued. The participants who are not transferred to the continuous treatment study after completion of the double-blind phase or after discontinuation during the double-blind phase will be transferred to the exit period (up to 1 week).The participants who complete the exit period will be transferred to the follow-up period, and a follow-up of the participant's safety and headache symptoms such as the migraine period rate will be conducted for 4 weeks after the completion of investigational treatment. Meanwhile, the participants who complete the double-blind phase or those who discontinue the study at Week 4 or later in the fixed-dose period during the double-blind phase due to lack of efficacy and give consent to transfer to the continuous treatment study will be transferred to the transfer period (up to 3 weeks) under blind conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who meet the Second Edition of the International Classification of Headache Disorders (ICHD-II), 1.1 Migraine without aura or 1.2 Migraine with aura over at least 6 months before the time of informed consent
- •Participants who had an average of no more than 8 migraine attacks per month during 3 months before informed consent and an average of no more than 14 headache (migraine and non-migraine) days
- •Participants whose number of migraine attacks during the baseline determination period (28 days) is 3 to 12 according to the 24-hour rule and number of headache days (migraine and non-migraine) is no more than 14
- •Participants who took no migraine preventive medications over 2 weeks before informed consent, or who can take at least 2-week washout period before baseline determination period if they are taking migraine preventive medications
- •Female participants must be postmenopausal, surgically sterile, abstinent, or can take adequate contraceptive measures after informed consent and continue it to the completion of investigational treatment
排除标准
- •Participants who cannot distinguish between migraine and non-migraine headache
- •Participants with headache other than those described in the ICHD-II, 1.1 Migraine without aura, 1.2 Migraine with aura,
- •Tension headache or 11.5 Sinus headache
- •If the participant has received drug therapies for prevention of migraine, the discontinued preventive therapies due to insufficient efficacy should be at least three types
- •Participants who excessively took medications for migraine attacks such as analgesics (drug used to control pain) as medications to be taken as needed within 3 months before informed consent
- •Participants who have taken topiramate (test drug in this study) in the past
研究组 & 干预措施
Topiramate (JNS019) 50 mg
In titration period, topiramate 25 milligram (mg) tablet will be given once daily in evening orally for 7 days; then topiramate 25 mg tablet twice daily orally from Day 8 to Day 14; then topiramate 25 mg tablet twice daily along with matching placebo tablet once daily in the evening orally from Day 15 to Day 21; then topiramate 25 mg tablet along with matching placebo tablet twice daily orally from Day 22 to Day 28 and will be continued further for 18 weeks in the fixed dose period.
干预措施: Topiramate (Drug)
Topiramate (JNS019) 50 mg
In titration period, topiramate 25 milligram (mg) tablet will be given once daily in evening orally for 7 days; then topiramate 25 mg tablet twice daily orally from Day 8 to Day 14; then topiramate 25 mg tablet twice daily along with matching placebo tablet once daily in the evening orally from Day 15 to Day 21; then topiramate 25 mg tablet along with matching placebo tablet twice daily orally from Day 22 to Day 28 and will be continued further for 18 weeks in the fixed dose period.
干预措施: Placebo (Drug)
Topiramate 100 mg
In titration period, topiramate 25 mg tablet will be given once daily in the evening orally for 7 days; then topiramate 25 mg tablet twice daily orally from Day 8 to Day 14; then topiramate 25 mg tablet twice daily (1 tablet in the morning and 2 tablets in the evening) orally from Day 15 to Day 21; then 2 topiramate 25 mg tablets twice daily orally from Day 22 to Day 28 and will be continued further for 18 weeks in the fixed dose period.
干预措施: Topiramate (Drug)
Placebo
In titration period, matching placebo tablet will be given once daily in evening orally for 7 days; followed by matching placebo tablet twice daily orally from Day 8 to Day 14; followed by matching placebo tablet twice daily (1 tablet in the morning and 2 tablets in the evening) orally from Day 15 to Day 21; followed by 2 matching placebo tablets twice orally from Day 22 to Day 28 and will becontinued further for 18 weeks in the fixed dose period.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in Monthly Migraine Attacks (According to 24-Hour Rule) Through Month 6
时间窗: Baseline (28 days before randomization) through Month 6
As per 24-hour rule, if symptom of pain due to migraine continues for more than 24 hours, it should be considered as 2 or more migraine attacks considering the maximum duration up to 24 hours. If the interval between latest migraine attack (ending time) and previous migraine attack (onset time) is less than 24 hours, 2 migraine attacks should be considered as 1 migraine attack. If the onset of migraine was prevented by a rescue drug, it should be considered as 1 migraine attack even if aura had started. Mean change was calculated by subtracting baseline value from the mean of 6 months value.
次要结局
- Percentage of Participants With Response to Study Treatment(Month 1, 2, 3, 4, 5 and 6)
- Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6(Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6)
- Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6(Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6)
- Change From Baseline in Average Number of Monthly Migraine Attacks (According to the Diagnostic Criteria of the International Headache Society) at Month 1, 2, 3, 4, 5 and 6(Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6)
- Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6(Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6)
- Change From Baseline in Migraine Attacks (According to 24-Hour Rule) Over Week 19 to Week 22 Period(Baseline (28 days before randomization), Week 19 to Week 22 Period)
- Average Number of Rescue Drug Treatment Days(Baseline (28 days before randomization))
- Change From Baseline in the Average Number of Rescue Drug Treatment Days at Month 6(Month 6)
- Short Form-36 Health Survey (SF-36) Score(Baseline (28 days before randomization), Day 29, 85 and final evaluation (FE) (Day 155/early withdrawal [EW]))