Migraine
Conditions
Keywords
Migraine, Topiramate
Brief summary
The purpose of this study is to evaluate the safety and efficacy of topiramate in participants with migraine (type of severe headache that occurs periodically and is often associated with nausea, vomiting and constipation or diarrhea) who completed the JNS019-JPN-02 study.
Detailed description
This is an open-label (all people know the identity of the intervention), multicenter (conducted in more than one center), dose-titration (dose escalation/reduction) study of topiramate in participants with migraine. This study is a continuous study for the participants who were enrolled in the JNS019-JPN-02 study. Participants who completed the JNS019-JPN-02 study will receive treatment for 52 weeks starting at Visit 4 of the JNS019-JPN-02 study. The present study will consist of 3 weeks of Transfer period (during this period the dose titration will take place and along with dose titration the new treatment will be initiated at 25 milligram per day \[25mg/day\]), Continuous treatment period (32 weeks), Exit period (up to 3 weeks) and Follow-up period (4 weeks). Participants in the Continuous treatment period will receive topiramate tablets orally in the dose range of 50 mg/day to 100 mg/day. Dose can be increased or decreased as per Investigator's discretion. The maximum daily dose will be 200 mg/day. Efficacy will be primarily evaluated by change from Baseline in the number of monthly migraine attacks in Continuous treatment period. Participants' safety will be monitored throughout the study.
Interventions
DRUGTopiramate
Topiramate tablets will be administered orally in the dose range of 50 to100 milligram per day (mg/day). Dose will be increased or decreased as per Investigator's discretion. Maximum daily dose limit will be 200 mg.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Participants who completed the JNS019-JPN-02 study or discontinued the study at Week 4 or after in fixed-dose period because of insufficient efficacy
Exclusion criteria
* Participants who discontinued the JNS019-JPN-02 study for an adverse event unrelated to the underlying disease * Participants judged unfavorable to be transferred to this study because of the safety assessments in the JNS019-JPN-02 study * Pregnant (carrying an unborn baby) female participants * Other participants who were considered ineligible as per Investigator's discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Baseline up to 28 days after last dose of study drug | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | Migraine:disabling headache disorder;2 major subtypes:migraine without aura(at least 5 attacks for 4-72 hours with at least 2 characteristics: unilateral location,pulsating quality,moderate/severe pain intensity or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia,phonophobia);migraine with aura(attack with reversible focal neurological symptoms that develop over 5-20 minutes, last for less than 60 minutes);average=total number of migraine attack days divided by total number of days of assessment and multiplied by 28,where a month=28 days. |
| Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | Migraine headache day was defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Average was calculated as total number of monthly headache days divided by total number of days of assessment and multiplied by 28, where a month was considered to last 28 days. |
| Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | Migraine has 2 major subtypes: migraine without aura (minimum 5 attacks of headache lasting for 4-72 hours, has 2 of these characteristics \[unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity\] and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (2 attacks of headache with typical aura with migraine headache or typical aura with non-migraine headache or typical aura without headache or familial hemiplegic migraine or sporadic hemiplegic migraine or basilar-type migraine). |
| Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | As per 48-hour rule, if the symptom of pain because of 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, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started. |
| Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | As per 24-hour rule, if symptom of pain because of 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 interval between the latest migraine attack (ending time) and previous migraine attack (onset time) was less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started. |
| Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Baseline (28 days before randomization) and FE (Day 225/early discontinuation) | The SF-36 is a standardized survey evaluating 8 domains (consisting of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Final evaluation (FE) was done at Day 225 or at discontinuation. |
| Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225) | If aura of migraine, migraine attack or non-migraine headache attack occurred in study, these rescue drugs were permitted:analgesics, non-steroidal anti-inflammatory drugs (NSAIDs),ergotamines,triptans,antiemetics. Drugs with restricted treatment days of less than (\<) 15 days per month (28 days):analgesics, NSAIDs,combination of rescue drugs and those with \<10 days per month:triptans,ergotamines, opioids,combination analgesics. Average calculated as total number of monthly rescue-drug treatment days divided by the total number of days of assessment and multiplied by 28, where a month = 28 days. |
| Percentage of Participants With Response to Treatment | Baseline (28 days before randomization) up to Day 225 | Responders were defined as participants who had a 50 percent or more reduction in frequency of migraine attacks. Migraine is common disabling headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 characteristics: unilateral location, pulsating quality, moderate/severe pain or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (attack with reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes). |
| Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Baseline (28 days before randomization) and Day 197 to Day 225 | As per 24-hour rule, if symptom of pain because of 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 interval between the latest migraine attack (ending time) and previous migraine attack (onset time) is less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started. |
Countries
Japan
Participant flow
Recruitment details
Present study is continuation of previous study (JNS019-JPN-02, NCT01081795). The participants who completed the previous study or the cases where the administration of study drug was discontinued because of insufficient results were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Topiramate (JNS019) Participants allocated to placebo group in the JNS019-JPN-02 trial were switched to active treatment in the current study JNS019-JPN-03. Participants received topiramate oral tablets twice daily in the dose range of 50 milligram (mg) to 100 mg. Dose was increased or decreased maximum up to 200 mg per day as per Investigators discretion. Total duration of treatment was 52 weeks. | 111 |
| Topiramate (JNS019) 50 mg Participants allocated to JNS019 50 mg group in JNS019-JPN-02 trial were switched to the dose range from 50 mg per day to 100 mg per day. Topiramate 25 mg oral tablets were administered twice daily. Dose was increased or decreased maximum up to 200 mg per day as per Investigators discretion. Total duration of treatment was 52 weeks. | 94 |
| Topiramate (JNS019) 100 mg Participants allocated to JNS019 100 mg group in JNS019-JPN-02 trial were switched to the dose range from 50 mg per day to 100 mg per day.Topiramate 50 mg oral tablets were administered twice daily. Dose was increased or decreased maximum up to 200 mg per day as per Investigators discretion. Total duration of treatment was 52 weeks. | 91 |
| Total | 296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 13 | 7 | 5 |
| Overall Study | Aggravation of complications | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 | 3 |
| Overall Study | Other | 3 | 0 | 1 |
| Overall Study | Participants convenience | 4 | 4 | 2 |
| Overall Study | Pregnancy | 2 | 0 | 0 |
| Overall Study | Use of prohibited concomitant drugs | 1 | 0 | 0 |
| Overall Study | Using drugs with restricted days of use | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Topiramate (JNS019) 100 mg | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Total |
|---|---|---|---|---|
| Age Continuous | 38.3 Years STANDARD_DEVIATION 9.12 | 41.5 Years STANDARD_DEVIATION 8.83 | 40.7 Years STANDARD_DEVIATION 9.28 | 40.3 Years STANDARD_DEVIATION 9.13 |
| Sex: Female, Male Female | 66 Participants | 92 Participants | 74 Participants | 232 Participants |
| Sex: Female, Male Male | 25 Participants | 19 Participants | 20 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 110 / 111 | 85 / 94 | 79 / 91 |
| serious Total, serious adverse events | 3 / 111 | 0 / 94 | 2 / 91 |
Outcome results
Primary
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Baseline up to 28 days after last dose of study drug
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Topiramate (JNS019) | Number of Participants With Adverse Events | 110 Participants |
| Topiramate (JNS019) 50 mg | Number of Participants With Adverse Events | 85 Participants |
| Topiramate (JNS019) 100 mg | Number of Participants With Adverse Events | 79 Participants |
Secondary
Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period
Migraine has 2 major subtypes: migraine without aura (minimum 5 attacks of headache lasting for 4-72 hours, has 2 of these characteristics \[unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity\] and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (2 attacks of headache with typical aura with migraine headache or typical aura with non-migraine headache or typical aura without headache or familial hemiplegic migraine or sporadic hemiplegic migraine or basilar-type migraine).
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Baseline (28 days before randomization) | 4.7 Migraine attacks | Standard Deviation 2.94 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Change during Continuous treatment period | -1.9 Migraine attacks | Standard Deviation 2.39 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Baseline (28 days before randomization) | 4.6 Migraine attacks | Standard Deviation 2.33 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Change during Continuous treatment period | -1.6 Migraine attacks | Standard Deviation 2.4 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Baseline (28 days before randomization) | 4.6 Migraine attacks | Standard Deviation 2.89 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period | Change during Continuous treatment period | -1.6 Migraine attacks | Standard Deviation 2.25 |
Secondary
Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period
Migraine headache day was defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Average was calculated as total number of monthly headache days divided by total number of days of assessment and multiplied by 28, where a month was considered to last 28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Baseline (28 days before randomization) | 7.5 Days | Standard Deviation 2.73 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Change during Continuous treatment period | -2.6 Days | Standard Deviation 2.75 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Baseline (28 days before randomization) | 6.8 Days | Standard Deviation 2.07 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Change during Continuous treatment period | -1.2 Days | Standard Deviation 3.28 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Baseline (28 days before randomization) | 7.2 Days | Standard Deviation 2.36 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period | Change during Continuous treatment period | -2.1 Days | Standard Deviation 2.52 |
Secondary
Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period
Migraine:disabling headache disorder;2 major subtypes:migraine without aura(at least 5 attacks for 4-72 hours with at least 2 characteristics: unilateral location,pulsating quality,moderate/severe pain intensity or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia,phonophobia);migraine with aura(attack with reversible focal neurological symptoms that develop over 5-20 minutes, last for less than 60 minutes);average=total number of migraine attack days divided by total number of days of assessment and multiplied by 28,where a month=28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Baseline (28 days before randomization) | 7.3 Days | Standard Deviation 2.56 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Change during Continuous treatment period | -2.4 Days | Standard Deviation 2.78 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Baseline (28 days before randomization) | 6.5 Days | Standard Deviation 2.09 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Change during Continuous treatment period | -1.1 Days | Standard Deviation 3.24 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Baseline (28 days before randomization) | 6.7 Days | Standard Deviation 2.16 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period | Change during Continuous treatment period | -1.9 Days | Standard Deviation 2.44 |
Secondary
Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period
If aura of migraine, migraine attack or non-migraine headache attack occurred in study, these rescue drugs were permitted:analgesics, non-steroidal anti-inflammatory drugs (NSAIDs),ergotamines,triptans,antiemetics. Drugs with restricted treatment days of less than (\<) 15 days per month (28 days):analgesics, NSAIDs,combination of rescue drugs and those with \<10 days per month:triptans,ergotamines, opioids,combination analgesics. Average calculated as total number of monthly rescue-drug treatment days divided by the total number of days of assessment and multiplied by 28, where a month = 28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Baseline (28 days before randomization) | 5.9 Days | Standard Deviation 2.35 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Change during Continuous treatment period | -1.6 Days | Standard Deviation 2.43 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Baseline (28 days before randomization) | 5.5 Days | Standard Deviation 2.21 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Change during Continuous treatment period | -0.7 Days | Standard Deviation 3.08 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Baseline (28 days before randomization) | 5.2 Days | Standard Deviation 2.26 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period | Change during Continuous treatment period | -1.0 Days | Standard Deviation 2.16 |
Secondary
Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period
As per 24-hour rule, if symptom of pain because of 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 interval between the latest migraine attack (ending time) and previous migraine attack (onset time) is less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Day 197 to Day 225
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Baseline (28 days before randomization) | 6.5 Migraine attacks | Standard Deviation 2.27 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Change during Day 197 to 225 | -1.9 Migraine attacks | Standard Deviation 2.87 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Baseline (28 days before randomization) | 5.9 Migraine attacks | Standard Deviation 1.76 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Change during Day 197 to 225 | -1.1 Migraine attacks | Standard Deviation 3.33 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Baseline (28 days before randomization) | 6.0 Migraine attacks | Standard Deviation 1.91 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period | Change during Day 197 to 225 | -1.4 Migraine attacks | Standard Deviation 2.68 |
Secondary
Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period
As per 24-hour rule, if symptom of pain because of 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 interval between the latest migraine attack (ending time) and previous migraine attack (onset time) was less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Baseline (28 days before randomization) | 6.5 Migraine attacks | Standard Deviation 2.27 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Change during Continuous treatment period | -2.1 Migraine attacks | Standard Deviation 2.47 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Baseline (28 days before randomization) | 5.9 Migraine attacks | Standard Deviation 1.76 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Change during Continuous treatment period | -1.0 Migraine attacks | Standard Deviation 3.21 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Baseline (28 days before randomization) | 6.0 Migraine attacks | Standard Deviation 1.91 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period | Change during Continuous treatment period | -1.6 Migraine attacks | Standard Deviation 2.11 |
Secondary
Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period
As per 48-hour rule, if the symptom of pain because of 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, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Baseline (28 days before randomization) | 5.0 Migraine attacks | Standard Deviation 1.58 |
| Placebo/Topiramate (JNS019) | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Change during Continuous treatment period | -1.6 Migraine attacks | Standard Deviation 1.76 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Baseline (28 days before randomization) | 4.6 Migraine attacks | Standard Deviation 1.23 |
| Topiramate (JNS019) 50 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Change during Continuous treatment period | -0.9 Migraine attacks | Standard Deviation 1.91 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Baseline (28 days before randomization) | 4.8 Migraine attacks | Standard Deviation 1.41 |
| Topiramate (JNS019) 100 mg | Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period | Change during Continuous treatment period | -1.3 Migraine attacks | Standard Deviation 1.6 |
Secondary
Percentage of Participants With Response to Treatment
Responders were defined as participants who had a 50 percent or more reduction in frequency of migraine attacks. Migraine is common disabling headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 characteristics: unilateral location, pulsating quality, moderate/severe pain or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (attack with reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes).
Time frame: Baseline (28 days before randomization) up to Day 225
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Topiramate (JNS019) | Percentage of Participants With Response to Treatment | 36.0 Percentage of participants |
| Topiramate (JNS019) 50 mg | Percentage of Participants With Response to Treatment | 18.1 Percentage of participants |
| Topiramate (JNS019) 100 mg | Percentage of Participants With Response to Treatment | 22.0 Percentage of participants |
Secondary
Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score
The SF-36 is a standardized survey evaluating 8 domains (consisting of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Final evaluation (FE) was done at Day 225 or at discontinuation.
Time frame: Baseline (28 days before randomization) and FE (Day 225/early discontinuation)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: Baseline (n=111,94,91) | 50.95 Units on a scale | Standard Deviation 8.728 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: FE (n=109,89,91) | 49.75 Units on a scale | Standard Deviation 9.373 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: Baseline (n=111,94,91) | 54.06 Units on a scale | Standard Deviation 5.957 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): FE (n=109,89,91) | 48.59 Units on a scale | Standard Deviation 10.273 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: Baseline (n=111,94,91) | 49.43 Units on a scale | Standard Deviation 8.392 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): FE (n=109,89,91) | 45.50 Units on a scale | Standard Deviation 11.22 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): Baseline (n=111,94,91) | 51.23 Units on a scale | Standard Deviation 8.862 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: FE (n=109,89,91) | 48.85 Units on a scale | Standard Deviation 9.468 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary : FE (n=109,89,91) | 47.73 Units on a scale | Standard Deviation 9.471 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: FE (n=109,89,91) | 46.23 Units on a scale | Standard Deviation 11.405 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: Baseline (n=111,94,91) | 47.49 Units on a scale | Standard Deviation 10.373 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: FE (n=109,89,91) | 48.10 Units on a scale | Standard Deviation 9.989 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: Baseline (n=111,94,91) | 39.90 Units on a scale | Standard Deviation 9.496 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary: Baseline (n=111,94,91) | 48.3 Units on a scale | Standard Deviation 7.923 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: Baseline (n=111,94,91) | 48.37 Units on a scale | Standard Deviation 7.425 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: FE (n=109,89,91) | 43.07 Units on a scale | Standard Deviation 9.744 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): Baseline (n=111,94,91) | 45.81 Units on a scale | Standard Deviation 9.556 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: FE (n=109,89,91) | 48.16 Units on a scale | Standard Deviation 9.836 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: Baseline (n=111,94,91) | 48.01 Units on a scale | Standard Deviation 7.526 |
| Placebo/Topiramate (JNS019) | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: FE (n=109,89,91) | 53.14 Units on a scale | Standard Deviation 8.269 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: FE (n=109,89,91) | 49.22 Units on a scale | Standard Deviation 8.982 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: Baseline (n=111,94,91) | 53.52 Units on a scale | Standard Deviation 5.033 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: FE (n=109,89,91) | 54.35 Units on a scale | Standard Deviation 5.648 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): Baseline (n=111,94,91) | 45.45 Units on a scale | Standard Deviation 9.909 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): FE (n=109,89,91) | 45.96 Units on a scale | Standard Deviation 9.789 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: Baseline (n=111,94,91) | 41.06 Units on a scale | Standard Deviation 8.274 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: FE (n=109,89,91) | 43.95 Units on a scale | Standard Deviation 10.725 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: Baseline (n=111,94,91) | 47.65 Units on a scale | Standard Deviation 8.895 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: FE (n=109,89,91) | 47.07 Units on a scale | Standard Deviation 9.564 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: Baseline (n=111,94,91) | 48.73 Units on a scale | Standard Deviation 7.849 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: FE (n=109,89,91) | 48.10 Units on a scale | Standard Deviation 9.796 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: Baseline (n=111,94,91) | 47.71 Units on a scale | Standard Deviation 9.959 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: FE (n=109,89,91) | 46.74 Units on a scale | Standard Deviation 10.349 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): Baseline (n=111,94,91) | 51.34 Units on a scale | Standard Deviation 7.879 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): FE (n=109,89,91) | 48.51 Units on a scale | Standard Deviation 9.271 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: Baseline (n=111,94,91) | 50.55 Units on a scale | Standard Deviation 8.017 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: FE (n=109,89,91) | 47.86 Units on a scale | Standard Deviation 9.514 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: Baseline (n=111,94,91) | 48.42 Units on a scale | Standard Deviation 7.497 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary: Baseline (n=111,94,91) | 48.06 Units on a scale | Standard Deviation 7.682 |
| Topiramate (JNS019) 50 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary : FE (n=109,89,91) | 46.49 Units on a scale | Standard Deviation 46.49 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: FE (n=109,89,91) | 54.79 Units on a scale | Standard Deviation 6.184 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): FE (n=109,89,91) | 49.53 Units on a scale | Standard Deviation 9.173 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: Baseline (n=111,94,91) | 49.39 Units on a scale | Standard Deviation 8.413 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary : FE (n=109,89,91) | 48.36 Units on a scale | Standard Deviation 9.087 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: Baseline (n=111,94,91) | 50.80 Units on a scale | Standard Deviation 7.958 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: FE (n=109,89,91) | 43.87 Units on a scale | Standard Deviation 9.861 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental component summary: Baseline (n=111,94,91) | 49.23 Units on a scale | Standard Deviation 7.383 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Mental health: FE (n=109,89,91) | 49.64 Units on a scale | Standard Deviation 9.801 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body pain: Baseline (n=111,94,91) | 42.77 Units on a scale | Standard Deviation 10.549 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Body function: Baseline (n=111,94,91) | 54.10 Units on a scale | Standard Deviation 8.374 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: Baseline (n=111,94,91) | 49.05 Units on a scale | Standard Deviation 9.455 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): FE (n=109,89,91) | 47.34 Units on a scale | Standard Deviation 9.804 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: Baseline (n=111,94,91) | 49.07 Units on a scale | Standard Deviation 9.891 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: FE (n=109,89,91) | 48.18 Units on a scale | Standard Deviation 9.644 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (physical): Baseline (n=111,94,91) | 46.15 Units on a scale | Standard Deviation 10.916 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Social activities: FE (n=109,89,91) | 50.22 Units on a scale | Standard Deviation 8.318 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Energy: Baseline (n=111,94,91) | 49.84 Units on a scale | Standard Deviation 7.269 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Physical component summary: FE (n=109,89,91) | 50.17 Units on a scale | Standard Deviation 7.718 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Daily activity (mental): Baseline (n=111,94,91) | 51.36 Units on a scale | Standard Deviation 8.99 |
| Topiramate (JNS019) 100 mg | Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score | Overall health: FE (n=109,89,91) | 50.72 Units on a scale | Standard Deviation 9.622 |