A Phase 2 interventional study of Topiramate in Migraine, sponsored by Janssen Pharmaceutical K.K.. Completed at 25 sites in Japan. Open to participants aged 20 Years to 65 Years. Per ClinicalTrials.gov, last updated 2013-05-31.
Sponsored by Janssen Pharmaceutical K.K. · Phase 2, Interventional, and Treatment
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.
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.
1,528 studies on the registry are indexed under Migraine Disorders; 299 are open to participants now.
This study's enrollment of 296 is above the median of 80 across 1,175 interventional studies indexed under Migraine Disorders.
Browse Migraine Disorders studies →Janssen Pharmaceutical K.K. is the lead sponsor of 122 studies on the registry; none are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 6 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Also known as: JNS019
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Baseline up to 28 days after last dose of study drug
Change From Baseline in the Number of Monthly Migraine Attacks as Per 24-hour Rule in the Continuous Treatment Period
As per 24-hour rule, if symptom of pain because of migraine continues for more than 24 hours, it should be considered as 2 or more migraine attacks considering the maximum duration up to 24 hours. If interval between the latest migraine attack (ending time) and previous migraine attack (onset time) was less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Change From Baseline in the Average Number of Monthly Migraine Attack Days in Continuous Treatment Period
Migraine:disabling headache disorder;2 major subtypes:migraine without aura(at least 5 attacks for 4-72 hours with at least 2 characteristics: unilateral location,pulsating quality,moderate/severe pain intensity or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia,phonophobia);migraine with aura(attack with reversible focal neurological symptoms that develop over 5-20 minutes, last for less than 60 minutes);average=total number of migraine attack days divided by total number of days of assessment and multiplied by 28,where a month=28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Change From Baseline in the Average Number of Monthly Headache Days in Continuous Treatment Period
Migraine headache day was defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Average was calculated as total number of monthly headache days divided by total number of days of assessment and multiplied by 28, where a month was considered to last 28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Change From Baseline in the Average Number of Migraine Attacks According to the Diagnostic Criteria of the International Headache Society Per Month in Continuous Treatment Period
Migraine has 2 major subtypes: migraine without aura (minimum 5 attacks of headache lasting for 4-72 hours, has 2 of these characteristics \[unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity\] and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (2 attacks of headache with typical aura with migraine headache or typical aura with non-migraine headache or typical aura without headache or familial hemiplegic migraine or sporadic hemiplegic migraine or basilar-type migraine).
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Change From Baseline in the Number of Monthly Migraine Attacks as Per 48-hour Rule in Continuous Treatment Period
As per 48-hour rule, if the symptom of pain because of migraine continues for more than 48 hours, it should be considered as 2 or more migraine attacks considering the maximum duration up to 48 hours. If the interval between the latest migraine attack (ending time) and the previous migraine attack (onset time) is less than 48 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Change From Baseline in the Number of Migraine Attacks as Per 24-hour Rule Over Day 197 to Day 225 in Continuous Treatment Period
As per 24-hour rule, if symptom of pain because of migraine continues for more than 24 hours, it should be considered as 2 or more migraine attacks considering the maximum duration up to 24 hours. If interval between the latest migraine attack (ending time) and previous migraine attack (onset time) is less than 24 hours, 2 migraine attacks were considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug it was considered as 1 migraine attack even if the aura had started.
Time frame: Baseline (28 days before randomization) and Day 197 to Day 225
Change From Baseline in the Average Number of Monthly Rescue-Drug Treatment Days in Continuous Treatment Period
If aura of migraine, migraine attack or non-migraine headache attack occurred in study, these rescue drugs were permitted:analgesics, non-steroidal anti-inflammatory drugs (NSAIDs),ergotamines,triptans,antiemetics. Drugs with restricted treatment days of less than (\<) 15 days per month (28 days):analgesics, NSAIDs,combination of rescue drugs and those with \<10 days per month:triptans,ergotamines, opioids,combination analgesics. Average calculated as total number of monthly rescue-drug treatment days divided by the total number of days of assessment and multiplied by 28, where a month = 28 days.
Time frame: Baseline (28 days before randomization) and Continuous treatment period (Day 1 up to Day 225)
Percentage of Participants With Response to Treatment
Responders were defined as participants who had a 50 percent or more reduction in frequency of migraine attacks. Migraine is common disabling headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 characteristics: unilateral location, pulsating quality, moderate/severe pain or aggravation by/causing avoidance of routine physical activity and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (attack with reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes).
Time frame: Baseline (28 days before randomization) up to Day 225
Quality of Life (QOL) Questionnaire (Short Form-36 [SF-36]) Score
The SF-36 is a standardized survey evaluating 8 domains (consisting of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Final evaluation (FE) was done at Day 225 or at discontinuation.
Time frame: Baseline (28 days before randomization) and FE (Day 225/early discontinuation)
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.
| Milestone | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| Started | 111 | 94 | 91 |
| Completed | 85 | 78 | 77 |
| Not completed | 26 | 16 | 14 |
| Withdrew: Adverse event | 13 | 7 | 5 |
| Withdrew: Pregnancy | 2 | 0 | 0 |
| Withdrew: Lack of efficacy | 3 | 1 | 3 |
| Withdrew: Participants convenience | 4 | 4 | 2 |
| Withdrew: Aggravation of complications | 0 | 1 | 1 |
| Withdrew: Using drugs with restricted days of use | 0 | 3 | 2 |
| Withdrew: Use of prohibited concomitant drugs | 1 | 0 | 0 |
| Withdrew: Other | 3 | 0 | 1 |
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.
| Participants | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| Number of Participants With Adverse Events | 110 | 85 | 79 |
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.
| Migraine attacks | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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.
| Days | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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.
| Days | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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).
| Migraine attacks | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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.
| Migraine attacks | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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.
| Migraine attacks | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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.
| Days | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
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).
| Percentage of participants | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| Percentage of Participants With Response to Treatment | 36.0 | 18.1 | 22.0 |
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.
| Units on a scale | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| 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 |
Collected over Baseline up to 28 days after last dose of study drug. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo/Topiramate (JNS019) | — | 3/111 (2.7%) | 110/111 (99.1%) |
| Topiramate (JNS019) 50 mg | — | 0/94 (0%) | 85/94 (90.4%) |
| Topiramate (JNS019) 100 mg | — | 2/91 (2.2%) | 79/91 (86.8%) |
| Event | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/111 | 0/94 | 1/91 |
| Ovarian neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/111 | 0/94 | 1/91 |
| Meniscus lesionInjury, poisoning and procedural complications | 0/111 | 0/94 | 1/91 |
| Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/111 | 0/94 | 0/91 |
| Rotator cuff syndromeMusculoskeletal and connective tissue disorders | 1/111 | 0/94 | 0/91 |
| MiscarriagePregnancy, puerperium and perinatal conditions | 1/111 | 0/94 | 0/91 |
| Event | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg |
|---|---|---|---|
| Laboratory testsGeneral disorders | 73/111 | 48/94 | 42/91 |
| Weight reductionGeneral disorders | 57/111 | 36/94 | 29/91 |
| NasopharyngitisInfections and infestations | 39/111 | 36/94 | 36/91 |
| DysesthesiaNervous system disorders | 42/111 | 15/94 | 11/91 |
| ParaesthesiaNervous system disorders | 32/111 | 12/94 | 8/91 |
| Decrease blood bicarbonateGeneral disorders | 20/111 | 16/94 | 5/91 |
| Inflammation of upper respiratory tractRespiratory, thoracic and mediastinal disorders | 14/111 | 12/94 | 14/91 |
| DiarrheaGastrointestinal disorders | 15/111 | 3/94 | 4/91 |
| FatigueGeneral disorders | 13/111 | 3/94 | 3/91 |
| Loss of appetiteMetabolism and nutrition disorders | 12/111 | 4/94 | 5/91 |
| Age Continuous(Years) | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg | Total |
|---|---|---|---|---|
| Mean | 41.5 ± 8.83 | 40.7 ± 9.28 | 38.3 ± 9.12 | 40.3 ± 9.13 |
| Sex: Female, Male(Participants) | Placebo/Topiramate (JNS019) | Topiramate (JNS019) 50 mg | Topiramate (JNS019) 100 mg | Total |
|---|---|---|---|---|
| Female | 92 | 74 | 66 | 232 |
| Male | 19 | 20 | 25 | 64 |
This study is completed, as verified in May 2013. You cannot join it, but the record below documents what was studied.
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Janssen Pharmaceutical K.K.