Continuous Treatment Study of Topiramate in Migraine Participants

• Sponsor: Janssen Pharmaceutical K.K. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01799590
• Collaborator: (none)
• Enrollment: 296
• Locations: 25
• Arm: 1
• Duration (Months): 27
• Patients Per Site: 11.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Topiramate	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 296 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Continuous Treatment Study of JNS019 (Topiramate) in Migraine Patients
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topiramate	Drug: Topiramate; 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.; Other Names: JNS019

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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).

5. 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.

6. 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.

7. 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.

8. 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).

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chitose		Japan
2		Hachioji		Japan
3		Isehara		Japan
4		Iwate		Japan
5		Kagoshima		Japan
6		Kamogawa		Japan
7		Kitakyushu		Japan
8		Kobe		Japan
9		Kumamoto		Japan
10		Kyoto		Japan
11		Minato		Japan
12		Morioka		Japan
13		Nagoya		Japan
14		Nishinomiya		Japan
15		Sagamihara N/A		Japan
16		Sapporo		Japan
17		Shinjuku-Ku		Japan
18		Shizuoka		Japan
19		Suginami-Ku		Japan
20		Tokyo		Japan
21		Toyama		Japan
22		Toyonaka		Japan
23		Ube		Japan
24		Yokohama		Japan
25		Yonago N/A		Japan

Sponsors and Collaborators

• Janssen Pharmaceutical K.K.

Investigators

• Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT01799590
• Other Study ID Numbers: CR013684; JNS019-JPN-03
• First Posted: Feb 27, 2013
• Last Update Posted: May 31, 2013
• Last Verified: May 1, 2013

• Keywords provided by Janssen Pharmaceutical K.K.: Migraine; Topiramate
• Additional relevant MeSH terms: Migraine Disorders; Topiramate

Study Results

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.

Arm/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	111	94	91
COMPLETED	85	78	77
NOT COMPLETED	26	16	14

Baseline Characteristics

Arm/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg	Total
Arm/Group Description	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.	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
Overall Participants	111	94	91	296
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.5 (8.83)	40.7 (9.28)	38.3 (9.12)	40.3 (9.13)
Sex: Female, Male (Count of Participants)
Female	92 82.9%	74 78.7%	66 72.5%	232 78.4%
Male	19 17.1%	20 21.3%	25 27.5%	64 21.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Number [Participants]	110 99.1%	85 90.4%	79 86.8%

2. Secondary Outcome

Title	Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	6.5 (2.27)	5.9 (1.76)	6.0 (1.91)
Change during Continuous treatment period	-2.1 (2.47)	-1.0 (3.21)	-1.6 (2.11)

3. Secondary Outcome

Title	Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	7.3 (2.56)	6.5 (2.09)	6.7 (2.16)
Change during Continuous treatment period	-2.4 (2.78)	-1.1 (3.24)	-1.9 (2.44)

4. Secondary Outcome

Title	Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	7.5 (2.73)	6.8 (2.07)	7.2 (2.36)
Change during Continuous treatment period	-2.6 (2.75)	-1.2 (3.28)	-2.1 (2.52)

5. Secondary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	4.7 (2.94)	4.6 (2.33)	4.6 (2.89)
Change during Continuous treatment period	-1.9 (2.39)	-1.6 (2.40)	-1.6 (2.25)

6. Secondary Outcome

Title	Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	5.0 (1.58)	4.6 (1.23)	4.8 (1.41)
Change during Continuous treatment period	-1.6 (1.76)	-0.9 (1.91)	-1.3 (1.60)

7. Secondary Outcome

Title	Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	6.5 (2.27)	5.9 (1.76)	6.0 (1.91)
Change during Day 197 to 225	-1.9 (2.87)	-1.1 (3.33)	-1.4 (2.68)

8. Secondary Outcome

Title	Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Baseline (28 days before randomization)	5.9 (2.35)	5.5 (2.21)	5.2 (2.26)
Change during Continuous treatment period	-1.6 (2.43)	-0.7 (3.08)	-1.0 (2.16)

9. Secondary Outcome

Title	Percentage of Participants With Response to Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Number [Percentage of participants]	36.0 32.4%	18.1 19.3%	22.0 24.2%

10. Secondary Outcome

Title	Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo/Topiramate (JNS019)	Topiramate (JNS019) 50 mg	Topiramate (JNS019) 100 mg
Arm/Group Description	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.	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.
Measure Participants	111	94	91
Body function: Baseline (n=111,94,91)	54.06 (5.957)	53.52 (5.033)	54.10 (8.374)
Body function: FE (n=109,89,91)	53.14 (8.269)	54.35 (5.648)	54.79 (6.184)
Daily activity (physical): Baseline (n=111,94,91)	45.81 (9.556)	45.45 (9.909)	46.15 (10.916)
Daily activity (physical): FE (n=109,89,91)	45.50 (11.220)	45.96 (9.789)	47.34 (9.804)
Body pain: Baseline (n=111,94,91)	39.90 (9.496)	41.06 (8.274)	42.77 (10.549)
Body pain: FE (n=109,89,91)	43.07 (9.744)	43.95 (10.725)	43.87 (9.861)
Overall health: Baseline (n=111,94,91)	48.01 (7.526)	47.65 (8.895)	49.39 (8.413)
Overall health: FE (n=109,89,91)	49.75 (9.373)	47.07 (9.564)	50.72 (9.622)
Energy: Baseline (n=111,94,91)	49.43 (8.392)	48.73 (7.849)	49.84 (7.269)
Energy: FE (n=109,89,91)	48.85 (9.468)	48.10 (9.796)	48.18 (9.644)
Social activities: Baseline (n=111,94,91)	47.49 (10.373)	47.71 (9.959)	49.07 (9.891)
Social activities: FE (n=109,89,91)	46.23 (11.405)	46.74 (10.349)	50.22 (8.318)
Daily activity (mental): Baseline (n=111,94,91)	51.23 (8.862)	51.34 (7.879)	51.36 (8.990)
Daily activity (mental): FE (n=109,89,91)	48.59 (10.273)	48.51 (9.271)	49.53 (9.173)
Mental health: Baseline (n=111,94,91)	50.95 (8.728)	50.55 (8.017)	50.80 (7.958)
Mental health: FE (n=109,89,91)	48.16 (9.836)	47.86 (9.514)	49.64 (9.801)
Physical component summary: Baseline (n=111,94,91)	48.37 (7.425)	48.42 (7.497)	49.05 (9.455)
Physical component summary: FE (n=109,89,91)	48.10 (9.989)	49.22 (8.982)	50.17 (7.718)
Mental component summary: Baseline (n=111,94,91)	48.3 (7.923)	48.06 (7.682)	49.23 (7.383)
Mental component summary : FE (n=109,89,91)	47.73 (9.471)	46.49 (46.49)	48.36 (9.087)

Adverse Events

Time Frame	Baseline up to 28 days after last dose of study drug
Arm/Group Title	Placebo/Topiramate (JNS019)		Topiramate (JNS019) 50 mg		Topiramate (JNS019) 100 mg
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo/Topiramate (JNS019)		Topiramate (JNS019) 50 mg		Topiramate (JNS019) 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo/Topiramate (JNS019)		Topiramate (JNS019) 50 mg		Topiramate (JNS019) 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/111 (2.7%)		0/94 (0%)		2/91 (2.2%)
Injury, poisoning and procedural complications
Meniscus lesion	0/111 (0%)		0/94 (0%)		1/91 (1.1%)
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	1/111 (0.9%)		0/94 (0%)		0/91 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/111 (0.9%)		0/94 (0%)		0/91 (0%)
Uterine leiomyoma	0/111 (0%)		0/94 (0%)		1/91 (1.1%)
Ovarian neoplasm	0/111 (0%)		0/94 (0%)		1/91 (1.1%)
Pregnancy, puerperium and perinatal conditions
Miscarriage	1/111 (0.9%)		0/94 (0%)		0/91 (0%)
Other (Not Including Serious) Adverse Events
	Placebo/Topiramate (JNS019)		Topiramate (JNS019) 50 mg		Topiramate (JNS019) 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/111 (99.1%)		85/94 (90.4%)		79/91 (86.8%)
Gastrointestinal disorders
Diarrhea	15/111 (13.5%)		3/94 (3.2%)		4/91 (4.4%)
Gastritis	8/111 (7.2%)		4/94 (4.3%)		7/91 (7.7%)
Abdominal pain	6/111 (5.4%)		5/94 (5.3%)		5/91 (5.5%)
Nausea	6/111 (5.4%)		5/94 (5.3%)		1/91 (1.1%)
Constipation	6/111 (5.4%)		2/94 (2.1%)		1/91 (1.1%)
Decayed tooth	1/111 (0.9%)		5/94 (5.3%)		2/91 (2.2%)
General disorders
Fatigue	13/111 (11.7%)		3/94 (3.2%)		3/91 (3.3%)
Laboratory tests	73/111 (65.8%)		48/94 (51.1%)		42/91 (46.2%)
Weight reduction	57/111 (51.4%)		36/94 (38.3%)		29/91 (31.9%)
Decrease blood bicarbonate	20/111 (18%)		16/94 (17%)		5/91 (5.5%)
Immune system disorders
Seasonal allergy	7/111 (6.3%)		5/94 (5.3%)		3/91 (3.3%)
Infections and infestations
Nasopharyngitis	39/111 (35.1%)		36/94 (38.3%)		36/91 (39.6%)
Gastroenteritis	8/111 (7.2%)		5/94 (5.3%)		4/91 (4.4%)
Cystitis	6/111 (5.4%)		3/94 (3.2%)		3/91 (3.3%)
Influenza	2/111 (1.8%)		1/94 (1.1%)		6/91 (6.6%)
Metabolism and nutrition disorders
Loss of appetite	12/111 (10.8%)		4/94 (4.3%)		5/91 (5.5%)
Musculoskeletal and connective tissue disorders
Backache	5/111 (4.5%)		2/94 (2.1%)		5/91 (5.5%)
Musculoskeletal stiffness	7/111 (6.3%)		2/94 (2.1%)		1/91 (1.1%)
Nervous system disorders
Dysesthesia	42/111 (37.8%)		15/94 (16%)		11/91 (12.1%)
Paraesthesia	32/111 (28.8%)		12/94 (12.8%)		8/91 (8.8%)
Drowsiness	11/111 (9.9%)		6/94 (6.4%)		7/91 (7.7%)
Dizziness	4/111 (3.6%)		1/94 (1.1%)		8/91 (8.8%)
Neuralgia	8/111 (7.2%)		1/94 (1.1%)		0/91 (0%)
Respiratory, thoracic and mediastinal disorders
Inflammation of upper respiratory tract	14/111 (12.6%)		12/94 (12.8%)		14/91 (15.4%)
Allergic rhinitis	1/111 (0.9%)		6/94 (6.4%)		1/91 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.