Trial Outcomes & Findings for Continuous Treatment Study of Topiramate in Migraine Participants (NCT NCT01799590)

Last Updated: 2013-05-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

296 participants

Primary outcome timeframe

Baseline up to 28 days after last dose of study drug

Results posted on

2013-05-31

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	111	94	91
Overall Study COMPLETED	85	78	77
Overall Study NOT COMPLETED	26	16	14

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Adverse Event	13	7	5
Overall Study Pregnancy	2	0	0
Overall Study Lack of Efficacy	3	1	3
Overall Study Participants convenience	4	4	2
Overall Study Aggravation of complications	0	1	1
Overall Study Using drugs with restricted days of use	0	3	2
Overall Study Use of prohibited concomitant drugs	1	0	0
Overall Study Other	3	0	1

Baseline Characteristics

Continuous Treatment Study of Topiramate in Migraine Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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 n=296 Participants Total of all reporting groups
Age Continuous	41.5 Years STANDARD_DEVIATION 8.83 • n=5 Participants	40.7 Years STANDARD_DEVIATION 9.28 • n=7 Participants	38.3 Years STANDARD_DEVIATION 9.12 • n=5 Participants	40.3 Years STANDARD_DEVIATION 9.13 • n=4 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	74 Participants n=7 Participants	66 Participants n=5 Participants	232 Participants n=4 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	20 Participants n=7 Participants	25 Participants n=5 Participants	64 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
Number of Participants With Adverse Events	110 Participants	85 Participants	79 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	5.9 Migraine attacks Standard Deviation 1.76	6.0 Migraine attacks Standard Deviation 1.91
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	-1.0 Migraine attacks Standard Deviation 3.21	-1.6 Migraine attacks Standard Deviation 2.11

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	6.5 Days Standard Deviation 2.09	6.7 Days Standard Deviation 2.16
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	-1.1 Days Standard Deviation 3.24	-1.9 Days Standard Deviation 2.44

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	6.8 Days Standard Deviation 2.07	7.2 Days Standard Deviation 2.36
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	-1.2 Days Standard Deviation 3.28	-2.1 Days Standard Deviation 2.52

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	4.6 Migraine attacks Standard Deviation 2.33	4.6 Migraine attacks Standard Deviation 2.89
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	-1.6 Migraine attacks Standard Deviation 2.40	-1.6 Migraine attacks Standard Deviation 2.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	4.6 Migraine attacks Standard Deviation 1.23	4.8 Migraine attacks Standard Deviation 1.41
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	-0.9 Migraine attacks Standard Deviation 1.91	-1.3 Migraine attacks Standard Deviation 1.60

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	5.9 Migraine attacks Standard Deviation 1.76	6.0 Migraine attacks Standard Deviation 1.91
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	-1.1 Migraine attacks Standard Deviation 3.33	-1.4 Migraine attacks Standard Deviation 2.68

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	5.5 Days Standard Deviation 2.21	5.2 Days Standard Deviation 2.26
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	-0.7 Days Standard Deviation 3.08	-1.0 Days Standard Deviation 2.16

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
Percentage of Participants With Response to Treatment	36.0 Percentage of participants	18.1 Percentage of participants	22.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo/Topiramate (JNS019) n=111 Participants 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.	Topiramate (JNS019) 50 mg n=94 Participants 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.	Topiramate (JNS019) 100 mg n=91 Participants 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.
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	48.51 Units on a scale Standard Deviation 9.271	49.53 Units on a scale Standard Deviation 9.173
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	53.52 Units on a scale Standard Deviation 5.033	54.10 Units on a scale Standard Deviation 8.374
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	54.35 Units on a scale Standard Deviation 5.648	54.79 Units on a scale Standard Deviation 6.184
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	45.45 Units on a scale Standard Deviation 9.909	46.15 Units on a scale Standard Deviation 10.916
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 11.220	45.96 Units on a scale Standard Deviation 9.789	47.34 Units on a scale Standard Deviation 9.804
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	41.06 Units on a scale Standard Deviation 8.274	42.77 Units on a scale Standard Deviation 10.549
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	43.95 Units on a scale Standard Deviation 10.725	43.87 Units on a scale Standard Deviation 9.861
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	47.65 Units on a scale Standard Deviation 8.895	49.39 Units on a scale Standard Deviation 8.413
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	47.07 Units on a scale Standard Deviation 9.564	50.72 Units on a scale Standard Deviation 9.622
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	48.73 Units on a scale Standard Deviation 7.849	49.84 Units on a scale Standard Deviation 7.269
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	48.10 Units on a scale Standard Deviation 9.796	48.18 Units on a scale Standard Deviation 9.644
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	47.71 Units on a scale Standard Deviation 9.959	49.07 Units on a scale Standard Deviation 9.891
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	46.74 Units on a scale Standard Deviation 10.349	50.22 Units on a scale Standard Deviation 8.318
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	51.34 Units on a scale Standard Deviation 7.879	51.36 Units on a scale Standard Deviation 8.990
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	50.55 Units on a scale Standard Deviation 8.017	50.80 Units on a scale Standard Deviation 7.958
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	47.86 Units on a scale Standard Deviation 9.514	49.64 Units on a scale Standard Deviation 9.801
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	48.42 Units on a scale Standard Deviation 7.497	49.05 Units on a scale Standard Deviation 9.455
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	49.22 Units on a scale Standard Deviation 8.982	50.17 Units on a scale Standard Deviation 7.718
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	48.06 Units on a scale Standard Deviation 7.682	49.23 Units on a scale Standard Deviation 7.383
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	46.49 Units on a scale Standard Deviation 46.49	48.36 Units on a scale Standard Deviation 9.087

Adverse Events

Placebo/Topiramate (JNS019)

Serious events: 3 serious events

Other events: 110 other events

Deaths: 0 deaths

Topiramate (JNS019) 50 mg

Serious events: 0 serious events

Other events: 85 other events

Deaths: 0 deaths

Topiramate (JNS019) 100 mg

Serious events: 2 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo/Topiramate (JNS019) n=111 participants at risk 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.	Topiramate (JNS019) 50 mg n=94 participants at risk 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.	Topiramate (JNS019) 100 mg n=91 participants at risk 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.90% 1/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	0.00% 0/91 • Baseline up to 28 days after last dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.00% 0/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.90% 1/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	0.00% 0/91 • Baseline up to 28 days after last dose of study drug
Pregnancy, puerperium and perinatal conditions Miscarriage	0.90% 1/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	0.00% 0/91 • Baseline up to 28 days after last dose of study drug
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/111 • Baseline up to 28 days after last dose of study drug	0.00% 0/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug

Other adverse events

Additional Information

Group Manager

Janssen Pharmaceutical KK Japan

Phone: +81-3-4411-5072

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on PI is that the Sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the Sponsor requires.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo/Topiramate (JNS019) n=111 participants at risk 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.	Topiramate (JNS019) 50 mg n=94 participants at risk 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.	Topiramate (JNS019) 100 mg n=91 participants at risk 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.
Infections and infestations Nasopharyngitis	35.1% 39/111 • Baseline up to 28 days after last dose of study drug	38.3% 36/94 • Baseline up to 28 days after last dose of study drug	39.6% 36/91 • Baseline up to 28 days after last dose of study drug
Infections and infestations Gastroenteritis	7.2% 8/111 • Baseline up to 28 days after last dose of study drug	5.3% 5/94 • Baseline up to 28 days after last dose of study drug	4.4% 4/91 • Baseline up to 28 days after last dose of study drug
Infections and infestations Cystitis	5.4% 6/111 • Baseline up to 28 days after last dose of study drug	3.2% 3/94 • Baseline up to 28 days after last dose of study drug	3.3% 3/91 • Baseline up to 28 days after last dose of study drug
Infections and infestations Influenza	1.8% 2/111 • Baseline up to 28 days after last dose of study drug	1.1% 1/94 • Baseline up to 28 days after last dose of study drug	6.6% 6/91 • Baseline up to 28 days after last dose of study drug
Immune system disorders Seasonal allergy	6.3% 7/111 • Baseline up to 28 days after last dose of study drug	5.3% 5/94 • Baseline up to 28 days after last dose of study drug	3.3% 3/91 • Baseline up to 28 days after last dose of study drug
Metabolism and nutrition disorders Loss of appetite	10.8% 12/111 • Baseline up to 28 days after last dose of study drug	4.3% 4/94 • Baseline up to 28 days after last dose of study drug	5.5% 5/91 • Baseline up to 28 days after last dose of study drug
Nervous system disorders Dysesthesia	37.8% 42/111 • Baseline up to 28 days after last dose of study drug	16.0% 15/94 • Baseline up to 28 days after last dose of study drug	12.1% 11/91 • Baseline up to 28 days after last dose of study drug
Nervous system disorders Paraesthesia	28.8% 32/111 • Baseline up to 28 days after last dose of study drug	12.8% 12/94 • Baseline up to 28 days after last dose of study drug	8.8% 8/91 • Baseline up to 28 days after last dose of study drug
Nervous system disorders Drowsiness	9.9% 11/111 • Baseline up to 28 days after last dose of study drug	6.4% 6/94 • Baseline up to 28 days after last dose of study drug	7.7% 7/91 • Baseline up to 28 days after last dose of study drug
Nervous system disorders Dizziness	3.6% 4/111 • Baseline up to 28 days after last dose of study drug	1.1% 1/94 • Baseline up to 28 days after last dose of study drug	8.8% 8/91 • Baseline up to 28 days after last dose of study drug
Nervous system disorders Neuralgia	7.2% 8/111 • Baseline up to 28 days after last dose of study drug	1.1% 1/94 • Baseline up to 28 days after last dose of study drug	0.00% 0/91 • Baseline up to 28 days after last dose of study drug
Respiratory, thoracic and mediastinal disorders Inflammation of upper respiratory tract	12.6% 14/111 • Baseline up to 28 days after last dose of study drug	12.8% 12/94 • Baseline up to 28 days after last dose of study drug	15.4% 14/91 • Baseline up to 28 days after last dose of study drug
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.90% 1/111 • Baseline up to 28 days after last dose of study drug	6.4% 6/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Diarrhea	13.5% 15/111 • Baseline up to 28 days after last dose of study drug	3.2% 3/94 • Baseline up to 28 days after last dose of study drug	4.4% 4/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Gastritis	7.2% 8/111 • Baseline up to 28 days after last dose of study drug	4.3% 4/94 • Baseline up to 28 days after last dose of study drug	7.7% 7/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Abdominal pain	5.4% 6/111 • Baseline up to 28 days after last dose of study drug	5.3% 5/94 • Baseline up to 28 days after last dose of study drug	5.5% 5/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Nausea	5.4% 6/111 • Baseline up to 28 days after last dose of study drug	5.3% 5/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Constipation	5.4% 6/111 • Baseline up to 28 days after last dose of study drug	2.1% 2/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
Gastrointestinal disorders Decayed tooth	0.90% 1/111 • Baseline up to 28 days after last dose of study drug	5.3% 5/94 • Baseline up to 28 days after last dose of study drug	2.2% 2/91 • Baseline up to 28 days after last dose of study drug
Musculoskeletal and connective tissue disorders Backache	4.5% 5/111 • Baseline up to 28 days after last dose of study drug	2.1% 2/94 • Baseline up to 28 days after last dose of study drug	5.5% 5/91 • Baseline up to 28 days after last dose of study drug
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	6.3% 7/111 • Baseline up to 28 days after last dose of study drug	2.1% 2/94 • Baseline up to 28 days after last dose of study drug	1.1% 1/91 • Baseline up to 28 days after last dose of study drug
General disorders Fatigue	11.7% 13/111 • Baseline up to 28 days after last dose of study drug	3.2% 3/94 • Baseline up to 28 days after last dose of study drug	3.3% 3/91 • Baseline up to 28 days after last dose of study drug
General disorders Laboratory tests	65.8% 73/111 • Baseline up to 28 days after last dose of study drug	51.1% 48/94 • Baseline up to 28 days after last dose of study drug	46.2% 42/91 • Baseline up to 28 days after last dose of study drug
General disorders Weight reduction	51.4% 57/111 • Baseline up to 28 days after last dose of study drug	38.3% 36/94 • Baseline up to 28 days after last dose of study drug	31.9% 29/91 • Baseline up to 28 days after last dose of study drug
General disorders Decrease blood bicarbonate	18.0% 20/111 • Baseline up to 28 days after last dose of study drug	17.0% 16/94 • Baseline up to 28 days after last dose of study drug	5.5% 5/91 • Baseline up to 28 days after last dose of study drug