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.

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.

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).

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.

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.

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.

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).

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.

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.

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.

Total of all reporting groups

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.

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.

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.

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.

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.

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 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.

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 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).

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 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.

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 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.

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.

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.

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 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).

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 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.

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.

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.

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.