Trial Outcomes & Findings for A Dose-Finding Study of Topiramate (JNS019) in Participants With Migraine (NCT NCT01081795)
NCT ID: NCT01081795
Last Updated: 2013-07-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
387 participants
Primary outcome timeframe
Baseline (28 days before randomization) through Month 6
Results posted on
2013-07-02
Participant Flow
Participant milestones
| Measure |
Topiramate (JNS019) 50 mg
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Overall Study
STARTED
|
130
|
130
|
127
|
|
Overall Study
COMPLETED
|
97
|
95
|
97
|
|
Overall Study
NOT COMPLETED
|
33
|
35
|
30
|
Reasons for withdrawal
| Measure |
Topiramate (JNS019) 50 mg
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
18
|
23
|
6
|
|
Overall Study
Lack of Efficacy
|
7
|
5
|
19
|
|
Overall Study
Subject's schedule
|
1
|
1
|
2
|
|
Overall Study
Revocation of informed consent
|
2
|
0
|
0
|
|
Overall Study
Ineligible for participation
|
1
|
0
|
0
|
|
Overall Study
Use of a prohibited concomitant drug
|
1
|
1
|
1
|
|
Overall Study
Using drug with restricted days of use
|
2
|
3
|
2
|
|
Overall Study
Other
|
1
|
2
|
0
|
Baseline Characteristics
A Dose-Finding Study of Topiramate (JNS019) in Participants With Migraine
Baseline characteristics by cohort
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
Total
n=387 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
40.4 Years
STANDARD_DEVIATION 9.30 • n=93 Participants
|
39.5 Years
STANDARD_DEVIATION 9.25 • n=4 Participants
|
41.2 Years
STANDARD_DEVIATION 9.10 • n=27 Participants
|
40.3 Years
STANDARD_DEVIATION 9.22 • n=483 Participants
|
|
Sex: Female, Male
Female
|
103 Participants
n=93 Participants
|
100 Participants
n=4 Participants
|
103 Participants
n=27 Participants
|
306 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
81 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline (28 days before randomization) through Month 6Population: Full analysis set (FAS) included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
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.
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Mean Change From Baseline in Monthly Migraine Attacks (According to 24-Hour Rule) Through Month 6
Baseline
|
5.9 Migraine attacks
Standard Deviation 1.79
|
6.2 Migraine attacks
Standard Deviation 2.11
|
6.6 Migraine attacks
Standard Deviation 2.29
|
|
Mean Change From Baseline in Monthly Migraine Attacks (According to 24-Hour Rule) Through Month 6
Change at Month 6
|
-0.9 Migraine attacks
Standard Deviation 2.50
|
-1.2 Migraine attacks
Standard Deviation 2.72
|
-1.0 Migraine attacks
Standard Deviation 2.42
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Migraine is a headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 following characteristics: unilateral location, pulsating quality, moderate/severe pain and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes); average at given month was calculated by dividing total number of migraine attack days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Baseline
|
6.6 Days
Standard Deviation 2.21
|
7.0 Days
Standard Deviation 2.35
|
7.3 Days
Standard Deviation 2.58
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 1
|
-0.5 Days
Standard Deviation 2.93
|
-0.8 Days
Standard Deviation 3.75
|
-0.4 Days
Standard Deviation 3.18
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 2
|
-0.7 Days
Standard Deviation 2.82
|
-1.1 Days
Standard Deviation 3.36
|
-0.7 Days
Standard Deviation 2.83
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 3
|
-0.9 Days
Standard Deviation 2.74
|
-1.2 Days
Standard Deviation 3.27
|
-0.9 Days
Standard Deviation 2.73
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 4
|
-0.9 Days
Standard Deviation 2.73
|
-1.3 Days
Standard Deviation 3.20
|
-1.0 Days
Standard Deviation 2.66
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 5
|
-1.0 Days
Standard Deviation 2.76
|
-1.3 Days
Standard Deviation 3.22
|
-1.0 Days
Standard Deviation 2.70
|
|
Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 6
|
-1.0 Days
Standard Deviation 2.83
|
-1.3 Days
Standard Deviation 3.24
|
-1.0 Days
Standard Deviation 2.72
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Headache days were the days when at least 30-minute migraine and non-migraine headache occurred and were calculated from the headache diaries kept by the participants. Average at given month was calculated by dividing total number of headache days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 6
|
-1.1 Days
Standard Deviation 2.89
|
-1.4 Days
Standard Deviation 3.18
|
-1.2 Days
Standard Deviation 2.70
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Baseline
|
6.9 Days
Standard Deviation 2.39
|
7.4 Days
Standard Deviation 2.48
|
7.7 Days
Standard Deviation 2.77
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 1
|
-0.6 Days
Standard Deviation 3.00
|
-0.8 Days
Standard Deviation 3.69
|
-0.4 Days
Standard Deviation 3.23
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 2
|
-0.8 Days
Standard Deviation 2.88
|
-1.2 Days
Standard Deviation 3.33
|
-0.8 Days
Standard Deviation 2.85
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 3
|
-1.0 Days
Standard Deviation 2.81
|
-1.3 Days
Standard Deviation 3.25
|
-0.9 Days
Standard Deviation 2.72
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 4
|
-1.1 Days
Standard Deviation 2.81
|
-1.4 Days
Standard Deviation 3.15
|
-1.1 Days
Standard Deviation 2.64
|
|
Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6
Change at Month 5
|
-1.1 Days
Standard Deviation 2.83
|
-1.4 Days
Standard Deviation 3.17
|
-1.2 Days
Standard Deviation 2.68
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Migraine is a headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 following characteristics: unilateral location, pulsating quality, moderate/severe pain and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes); average at given month was calculated by dividing total number of migraine attacks until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
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
|
4.1 Migraine attacks
Standard Deviation 2.25
|
4.3 Migraine attacks
Standard Deviation 2.94
|
4.2 Migraine attacks
Standard Deviation 2.93
|
|
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
Change at Month 1
|
-0.8 Migraine attacks
Standard Deviation 2.60
|
-0.4 Migraine attacks
Standard Deviation 2.92
|
-0.5 Migraine attacks
Standard Deviation 2.37
|
|
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
Change at Month 2
|
-0.9 Migraine attacks
Standard Deviation 2.61
|
-0.7 Migraine attacks
Standard Deviation 2.75
|
-0.7 Migraine attacks
Standard Deviation 2.27
|
|
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
Change at Month 3
|
-0.9 Migraine attacks
Standard Deviation 2.56
|
-0.8 Migraine attacks
Standard Deviation 2.71
|
-0.7 Migraine attacks
Standard Deviation 2.13
|
|
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
Change at Month 4
|
-1.0 Migraine attacks
Standard Deviation 2.54
|
-0.9 Migraine attacks
Standard Deviation 2.68
|
-0.8 Migraine attacks
Standard Deviation 2.15
|
|
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
Change at Month 5
|
-1.1 Migraine attacks
Standard Deviation 2.56
|
-0.9 Migraine attacks
Standard Deviation 2.69
|
-0.8 Migraine attacks
Standard Deviation 2.18
|
|
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
Change at Month 6
|
-1.1 Migraine attacks
Standard Deviation 2.59
|
-0.9 Migraine attacks
Standard Deviation 2.68
|
-0.8 Migraine attacks
Standard Deviation 2.17
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
As per 48-hour rule, if the symptom of pain due to migraine continues for more than 48 hours, it should be considered as 2 or more migraine attacks considering the maximum duration up to 48 hours. If the interval between the latest migraine attack (ending time) and the previous migraine attack (onset time) is less than 48 hours, the 2 migraine attacks should be considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug, it should be considered as 1 migraine attack even if the aura had started.
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Baseline
|
4.6 Migraine attacks
Standard Deviation 1.28
|
4.9 Migraine attacks
Standard Deviation 1.52
|
5.1 Migraine attacks
Standard Deviation 1.56
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 1
|
-0.2 Migraine attacks
Standard Deviation 1.94
|
-0.6 Migraine attacks
Standard Deviation 2.28
|
-0.3 Migraine attacks
Standard Deviation 1.93
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 2
|
-0.5 Migraine attacks
Standard Deviation 1.77
|
-0.8 Migraine attacks
Standard Deviation 2.03
|
-0.6 Migraine attacks
Standard Deviation 1.76
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 3
|
-0.6 Migraine attacks
Standard Deviation 1.73
|
-0.9 Migraine attacks
Standard Deviation 1.95
|
-0.7 Migraine attacks
Standard Deviation 1.70
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 4
|
-0.6 Migraine attacks
Standard Deviation 1.71
|
-1.0 Migraine attacks
Standard Deviation 1.90
|
-0.7 Migraine attacks
Standard Deviation 1.70
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 5
|
-0.7 Migraine attacks
Standard Deviation 1.72
|
-1.0 Migraine attacks
Standard Deviation 1.91
|
-0.8 Migraine attacks
Standard Deviation 1.71
|
|
Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6
Change at Month 6
|
-0.7 Migraine attacks
Standard Deviation 1.75
|
-1.0 Migraine attacks
Standard Deviation 1.92
|
-0.8 Migraine attacks
Standard Deviation 1.72
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Week 19 to Week 22 PeriodPopulation: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
The change from baseline in average number of migraine attacks (as per 24-hour rule) over Week 19 to Week 22 period was calculated by subtracting the baseline value from the average value of the Week 19 to Week 22 period.
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Change From Baseline in Migraine Attacks (According to 24-Hour Rule) Over Week 19 to Week 22 Period
|
-1.3 Migraine attacks
Standard Error 0.28
|
-1.2 Migraine attacks
Standard Error 0.28
|
-0.7 Migraine attacks
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization)Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Rescue medications are administered to participants when efficacy of study drug is not satisfactory, or effect of study drug is too great and is likely to cause a hazard to participant, or to manage an emergency situation. If an aura of migraine, a migraine attack or a non-migraine headache attack occurred during the study period, use of following rescue drugs was permitted: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), ergotamines, triptans and anti-emetics (drug used to stop vomiting). Average at baseline was calculated by dividing total number of rescue drug treatment days until baseline by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Average Number of Rescue Drug Treatment Days
|
5.5 Days
Standard Deviation 2.21
|
5.7 Days
Standard Deviation 2.50
|
6.1 Days
Standard Deviation 2.43
|
SECONDARY outcome
Timeframe: Month 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Rescue medications are medicines that may be administered to the participants when efficacy of study drug is not satisfactory, or the effect of study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. If an aura of migraine, a migraine attack or a non-migraine headache attack occurred during the study period, use of following rescue drugs was permitted: analgesics, NSAIDs, ergotamines, triptans and anti-emetics. Average at Month 6 was calculated by dividing total number of rescue drug treatment days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Change From Baseline in the Average Number of Rescue Drug Treatment Days at Month 6
|
-0.8 Days
Standard Error 0.21
|
-0.8 Days
Standard Error 0.21
|
-0.4 Days
Standard Error 0.22
|
SECONDARY outcome
Timeframe: Month 1, 2, 3, 4, 5 and 6Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization.
Responders were the participants who had at least 50 percent reduction in the average number of monthly migraine attacks.
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Percentage of Participants With Response to Study Treatment
Month 1
|
10.8 Percentage of participants
|
23.1 Percentage of participants
|
11.8 Percentage of participants
|
|
Percentage of Participants With Response to Study Treatment
Month 2
|
16.9 Percentage of participants
|
23.1 Percentage of participants
|
14.2 Percentage of participants
|
|
Percentage of Participants With Response to Study Treatment
Month 3
|
14.6 Percentage of participants
|
20.8 Percentage of participants
|
9.4 Percentage of participants
|
|
Percentage of Participants With Response to Study Treatment
Month 4
|
15.4 Percentage of participants
|
18.5 Percentage of participants
|
14.2 Percentage of participants
|
|
Percentage of Participants With Response to Study Treatment
Month 5
|
15.4 Percentage of participants
|
19.2 Percentage of participants
|
14.2 Percentage of participants
|
|
Percentage of Participants With Response to Study Treatment
Month 6
|
15.4 Percentage of participants
|
18.5 Percentage of participants
|
13.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (28 days before randomization), Day 29, 85 and final evaluation (FE) (Day 155/early withdrawal [EW])Population: The FAS included all participants randomly assigned to study treatment excluding those who did not meet eligibility criteria, did not receive study treatment at all and did not provide any efficacy data after randomization. Here 'n' signifies those participants who were evaluable for this measure at given time points.
The SF-36 is a survey of participant health. It consists of 8 scaled scores, which are weighted sums of the questions in their section. The 8 sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. Each item is scored on a 0-100 range so that total score ranges from 0-100 with high score indicating more favorable health state. Final evaluation was done at Day 155 or at discontinuation for those participants who discontinued before Day 155.
Outcome measures
| Measure |
Topiramate (JNS019) 50 mg
n=130 Participants
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 Participants
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 Participants
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Short Form-36 Health Survey (SF-36) Score
Role-Emotional: Baseline (n=130,130,127)
|
51.13 Units on a scale
Standard Deviation 7.916
|
51.22 Units on a scale
Standard Deviation 8.515
|
51.20 Units on a scale
Standard Deviation 8.500
|
|
Short Form-36 Health Survey (SF-36) Score
Social functioning: Day 85 (n=111,109,121)
|
45.89 Units on a scale
Standard Deviation 11.916
|
46.89 Units on a scale
Standard Deviation 10.454
|
49.10 Units on a scale
Standard Deviation 9.581
|
|
Short Form-36 Health Survey (SF-36) Score
Social functioning: FE (Day155/EW) (n=130,130,127)
|
45.81 Units on a scale
Standard Deviation 11.440
|
46.11 Units on a scale
Standard Deviation 11.475
|
49.01 Units on a scale
Standard Deviation 10.521
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Emotional: Day 29 (n=127,122,125)
|
48.82 Units on a scale
Standard Deviation 8.891
|
48.29 Units on a scale
Standard Deviation 10.837
|
51.69 Units on a scale
Standard Deviation 8.425
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Emotional: Day 85 (n=111,109,121)
|
49.27 Units on a scale
Standard Deviation 9.126
|
49.72 Units on a scale
Standard Deviation 8.104
|
51.60 Units on a scale
Standard Deviation 7.466
|
|
Short Form-36 Health Survey (SF-36) Score
Physical functioning: Baseline (n=130,130,127)
|
53.59 Units on a scale
Standard Deviation 5.029
|
53.84 Units on a scale
Standard Deviation 8.267
|
54.17 Units on a scale
Standard Deviation 5.669
|
|
Short Form-36 Health Survey (SF-36) Score
Physical functioning: Day 29 (n=127,122,125)
|
53.03 Units on a scale
Standard Deviation 6.459
|
53.15 Units on a scale
Standard Deviation 7.732
|
54.26 Units on a scale
Standard Deviation 5.520
|
|
Short Form-36 Health Survey (SF-36) Score
Physical functioning: Day 85 (n=111,109,121)
|
53.86 Units on a scale
Standard Deviation 5.989
|
53.85 Units on a scale
Standard Deviation 7.160
|
54.47 Units on a scale
Standard Deviation 5.437
|
|
Short Form-36 Health Survey (SF-36) Score
Physical functioning:FE (Day155/EW)(n=130,130,127)
|
54.02 Units on a scale
Standard Deviation 5.606
|
53.79 Units on a scale
Standard Deviation 7.643
|
54.40 Units on a scale
Standard Deviation 5.788
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Physical: Baseline (n=130,130,127)
|
46.10 Units on a scale
Standard Deviation 9.529
|
45.29 Units on a scale
Standard Deviation 11.095
|
45.86 Units on a scale
Standard Deviation 9.247
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Physical: Day 29 (n=127,122,125)
|
44.49 Units on a scale
Standard Deviation 10.892
|
46.05 Units on a scale
Standard Deviation 11.094
|
46.35 Units on a scale
Standard Deviation 9.700
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Physical: Day 85 (n=111,109,121)
|
45.88 Units on a scale
Standard Deviation 9.687
|
46.34 Units on a scale
Standard Deviation 10.320
|
46.95 Units on a scale
Standard Deviation 9.624
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Physical: FE (Day 155/EW) (n=130,130,127)
|
45.21 Units on a scale
Standard Deviation 10.675
|
45.69 Units on a scale
Standard Deviation 10.384
|
46.29 Units on a scale
Standard Deviation 9.230
|
|
Short Form-36 Health Survey (SF-36) Score
Bodily pain: Baseline (n=130,130,127)
|
40.75 Units on a scale
Standard Deviation 8.822
|
41.76 Units on a scale
Standard Deviation 10.171
|
39.67 Units on a scale
Standard Deviation 9.164
|
|
Short Form-36 Health Survey (SF-36) Score
Bodily pain: Day 29 (n=127,122,125)
|
42.98 Units on a scale
Standard Deviation 10.029
|
44.43 Units on a scale
Standard Deviation 10.352
|
41.17 Units on a scale
Standard Deviation 9.716
|
|
Short Form-36 Health Survey (SF-36) Score
Bodily pain: Day 85 (n=111,109,121)
|
43.09 Units on a scale
Standard Deviation 9.450
|
44.43 Units on a scale
Standard Deviation 9.923
|
42.03 Units on a scale
Standard Deviation 8.557
|
|
Short Form-36 Health Survey (SF-36) Score
Bodily pain: FE (Day 155/EW) (n=130,130,127)
|
42.64 Units on a scale
Standard Deviation 8.504
|
43.82 Units on a scale
Standard Deviation 9.906
|
42.87 Units on a scale
Standard Deviation 8.776
|
|
Short Form-36 Health Survey (SF-36) Score
General health: Baseline (n=130,130,127)
|
47.56 Units on a scale
Standard Deviation 8.444
|
48.92 Units on a scale
Standard Deviation 8.571
|
47.61 Units on a scale
Standard Deviation 7.894
|
|
Short Form-36 Health Survey (SF-36) Score
General health: Day 29 (n=127,122,125)
|
47.30 Units on a scale
Standard Deviation 8.996
|
49.21 Units on a scale
Standard Deviation 9.176
|
49.12 Units on a scale
Standard Deviation 7.904
|
|
Short Form-36 Health Survey (SF-36) Score
General health: Day 85 (n=111,109,121)
|
47.48 Units on a scale
Standard Deviation 8.827
|
48.70 Units on a scale
Standard Deviation 9.857
|
49.31 Units on a scale
Standard Deviation 8.053
|
|
Short Form-36 Health Survey (SF-36) Score
General health: FE (Day 155/EW) (n=130,130,127)
|
47.48 Units on a scale
Standard Deviation 8.459
|
48.12 Units on a scale
Standard Deviation 9.425
|
49.86 Units on a scale
Standard Deviation 8.713
|
|
Short Form-36 Health Survey (SF-36) Score
Vitality: Baseline (n=130,130,127)
|
48.91 Units on a scale
Standard Deviation 7.754
|
49.10 Units on a scale
Standard Deviation 7.765
|
49.17 Units on a scale
Standard Deviation 8.393
|
|
Short Form-36 Health Survey (SF-36) Score
Vitality: Day 29 (n=127,122,125)
|
47.72 Units on a scale
Standard Deviation 8.888
|
47.59 Units on a scale
Standard Deviation 9.900
|
50.78 Units on a scale
Standard Deviation 8.579
|
|
Short Form-36 Health Survey (SF-36) Score
Vitality: Day 85 (n=111,109,121)
|
48.45 Units on a scale
Standard Deviation 9.484
|
48.04 Units on a scale
Standard Deviation 9.375
|
49.40 Units on a scale
Standard Deviation 8.790
|
|
Short Form-36 Health Survey (SF-36) Score
Vitality: FE (Day 155/EW) (n=130,130,127)
|
47.73 Units on a scale
Standard Deviation 9.625
|
47.66 Units on a scale
Standard Deviation 9.850
|
50.34 Units on a scale
Standard Deviation 8.683
|
|
Short Form-36 Health Survey (SF-36) Score
Social functioning: Baseline (n=130,130,127)
|
47.62 Units on a scale
Standard Deviation 9.342
|
47.98 Units on a scale
Standard Deviation 10.108
|
47.82 Units on a scale
Standard Deviation 10.095
|
|
Short Form-36 Health Survey (SF-36) Score
Social functioning: Day 29 (n=127,122,125)
|
46.06 Units on a scale
Standard Deviation 10.178
|
46.25 Units on a scale
Standard Deviation 10.955
|
49.10 Units on a scale
Standard Deviation 9.865
|
|
Short Form-36 Health Survey (SF-36) Score
Role-Emotional: FE (Day 155/EW) (n=130,130,127)
|
48.38 Units on a scale
Standard Deviation 10.419
|
48.18 Units on a scale
Standard Deviation 9.941
|
50.80 Units on a scale
Standard Deviation 8.785
|
|
Short Form-36 Health Survey (SF-36) Score
Mental health: Baseline (n=130,130,127)
|
50.01 Units on a scale
Standard Deviation 7.632
|
50.34 Units on a scale
Standard Deviation 8.161
|
50.62 Units on a scale
Standard Deviation 8.457
|
|
Short Form-36 Health Survey (SF-36) Score
Mental health: Day 29 (n=127,122,125)
|
47.77 Units on a scale
Standard Deviation 8.793
|
46.33 Units on a scale
Standard Deviation 10.524
|
52.02 Units on a scale
Standard Deviation 8.417
|
|
Short Form-36 Health Survey (SF-36) Score
Mental health: Day 85 (n=111,109,121)
|
48.87 Units on a scale
Standard Deviation 9.402
|
47.18 Units on a scale
Standard Deviation 9.669
|
51.11 Units on a scale
Standard Deviation 8.021
|
|
Short Form-36 Health Survey (SF-36) Score
Mental health: FE (Day 155/EW) (n=130,130,127)
|
47.48 Units on a scale
Standard Deviation 10.270
|
48.19 Units on a scale
Standard Deviation 9.648
|
51.14 Units on a scale
Standard Deviation 8.322
|
Adverse Events
Topiramate (JNS019) 50 mg
Serious events: 2 serious events
Other events: 125 other events
Deaths: 0 deaths
Topiramate 100 mg
Serious events: 4 serious events
Other events: 121 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 106 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Topiramate (JNS019) 50 mg
n=130 participants at risk
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 participants at risk
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 participants at risk
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Infections and infestations
Shingles
|
0.77%
1/130
|
0.00%
0/130
|
0.00%
0/127
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/130
|
0.77%
1/130
|
0.00%
0/127
|
|
Psychiatric disorders
Depression
|
0.77%
1/130
|
0.00%
0/130
|
0.00%
0/127
|
|
Nervous system disorders
Migraine
|
0.00%
0/130
|
0.77%
1/130
|
0.00%
0/127
|
|
Nervous system disorders
Syncope
|
0.00%
0/130
|
0.00%
0/130
|
0.79%
1/127
|
|
Eye disorders
Closed-angle glaucoma
|
0.00%
0/130
|
0.77%
1/130
|
0.00%
0/127
|
|
Gastrointestinal disorders
Hemorrhagic gastritis
|
0.00%
0/130
|
0.00%
0/130
|
0.79%
1/127
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/130
|
0.00%
0/130
|
0.79%
1/127
|
|
Renal and urinary disorders
Ureterodialysis
|
0.00%
0/130
|
0.77%
1/130
|
0.00%
0/127
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/130
|
0.77%
1/130
|
0.00%
0/127
|
Other adverse events
| Measure |
Topiramate (JNS019) 50 mg
n=130 participants at risk
In titration period, topiramate 25 milligram (mg) tablet 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 continued further for 18 weeks in the fixed dose period
|
Topiramate 100 mg
n=130 participants at risk
In titration period, topiramate 25 mg tablet 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 continued further for 18 weeks in the fixed dose period
|
Placebo
n=127 participants at risk
In titration period, matching placebo tablet 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 daily orally from Day 22 to Day 28 and continued further for 18 weeks in the fixed dose period
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
34.6%
45/130
|
30.0%
39/130
|
29.1%
37/127
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.2%
8/130
|
8.5%
11/130
|
2.4%
3/127
|
|
Nervous system disorders
Paraesthesia
|
29.2%
38/130
|
38.5%
50/130
|
3.1%
4/127
|
|
Nervous system disorders
Dysaesthesia
|
26.9%
35/130
|
20.0%
26/130
|
5.5%
7/127
|
|
Nervous system disorders
Somnolence
|
16.2%
21/130
|
12.3%
16/130
|
11.8%
15/127
|
|
Nervous system disorders
Disturbance in attention
|
5.4%
7/130
|
3.1%
4/130
|
1.6%
2/127
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
10.0%
13/130
|
12.3%
16/130
|
7.9%
10/127
|
|
Gastrointestinal disorders
Diarrhoea
|
8.5%
11/130
|
5.4%
7/130
|
5.5%
7/127
|
|
Gastrointestinal disorders
Nausea
|
6.2%
8/130
|
4.6%
6/130
|
3.9%
5/127
|
|
General disorders
Malaise
|
6.2%
8/130
|
6.2%
8/130
|
4.7%
6/127
|
|
Investigations
Weight decreased
|
33.1%
43/130
|
39.2%
51/130
|
8.7%
11/127
|
|
Investigations
Blood bicarbonate decreased
|
8.5%
11/130
|
11.5%
15/130
|
0.79%
1/127
|
Additional Information
Group Manager
Janssen Pharmaceutical KK Japan
Phone: +81-3-4411-5072
Results disclosure agreements
- Principal investigator is a sponsor employee The disclosure restriction on PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the sponsor requires.
- Publication restrictions are in place
Restriction type: OTHER