Continuous Treatment Study of Topiramate in Migraine Participants

• ClinicalTrials.gov Identifier: NCT01799590
• Recruitment Status: Completed
• First Posted: February 27, 2013
• Results First Posted: May 6, 2013
• Last Update Posted: May 31, 2013
• Sponsor: Janssen Pharmaceutical K.K.
• Information provided by (Responsible Party): Janssen Pharmaceutical K.K.

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 (Clinical Trial)
• 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: August 2007
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: November 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 Name: JNS019

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Japan

Chitose, Japan

Hachioji, Japan

Isehara, Japan

Iwate, Japan

Kagoshima, Japan

Kamogawa, Japan

Kitakyushu, Japan

Kobe, Japan

Kumamoto, Japan

Kyoto, Japan

Minato, Japan

Morioka, Japan

Nagoya, Japan

Nishinomiya, Japan

Sagamihara N/A, Japan

Sapporo, Japan

Shinjuku-Ku, Japan

Shizuoka, Japan

Suginami-Ku, Japan

Tokyo, Japan

Toyama, Japan

Toyonaka, Japan

Ube, Japan

Yokohama, Japan

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.

More Information

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT01799590
• Other Study ID Numbers: CR013684; JNS019-JPN-03
• First Posted: February 27, 2013
• Results First Posted: May 6, 2013
• Last Update Posted: May 31, 2013
• Last Verified: May 2013

Keywords provided by Janssen Pharmaceutical K.K.:

Migraine; Topiramate

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Topiramate; Anticonvulsants; Hypoglycemic Agents; Physiological Effects of Drugs