A Dose-Finding Study of Topiramate (JNS019) in Participants With Migraine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01081795
First received: March 4, 2010
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine a recommended dose of topiramate in participants with migraine (type of severe headache that occurs periodically and is often associated with nausea, vomiting, and constipation or diarrhea), to verify the superiority (statistically more effective) of the drug to placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), and to assess if a same therapeutic effect can be observed between this study and overseas Caucasian clinical studies.


Condition Intervention Phase
Migraine
Drug: Topiramate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Dose-Finding Study of JNS019 (Topiramate) in Migraine Patients

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • Mean Change From Baseline in Monthly Migraine Attacks (According to 24-Hour Rule) Through Month 6 [ Time Frame: Baseline (28 days before randomization) through Month 6 ] [ Designated as safety issue: No ]
    As per 24-hour rule, if symptom of pain due to 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 the interval between latest migraine attack (ending time) and previous migraine attack (onset time) is less than 24 hours, 2 migraine attacks should be considered as 1 migraine attack. If the onset of migraine was prevented by a rescue drug, it should be considered as 1 migraine attack even if aura had started. Mean change was calculated by subtracting baseline value from the mean of 6 months value.


Secondary Outcome Measures:
  • Change From Baseline in Average Number of Monthly Migraine Attack Days at Month 1, 2, 3, 4, 5 and 6 [ Time Frame: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
    Migraine is a headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 following characteristics: unilateral location, pulsating quality, moderate/severe pain and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes); average at given month was calculated by dividing total number of migraine attack days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).

  • Change From Baseline in Average Number of Monthly Headache Days at Month 1, 2, 3, 4, 5 and 6 [ Time Frame: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
    Headache days were the days when at least 30-minute migraine and non-migraine headache occurred and were calculated from the headache diaries kept by the participants. Average at given month was calculated by dividing total number of headache days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).

  • Change From Baseline in Average Number of Monthly Migraine Attacks (According to the Diagnostic Criteria of the International Headache Society) at Month 1, 2, 3, 4, 5 and 6 [ Time Frame: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
    Migraine is a headache disorder with 2 subtypes: migraine without aura (at least 5 attacks lasting 4-72 hours with at least 2 following characteristics: unilateral location, pulsating quality, moderate/severe pain and either nausea/vomiting or photophobia and phonophobia) and migraine with aura (reversible focal neurological symptoms that develop over 5-20 minutes and last for less than 60 minutes); average at given month was calculated by dividing total number of migraine attacks until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).

  • Change From Baseline in Monthly Migraine Attacks (According to 48-Hour Rule) at Month 1, 2, 3, 4, 5 and 6 [ Time Frame: Baseline (28 days before randomization), Month 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
    As per 48-hour rule, if the symptom of pain due to 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, the 2 migraine attacks should be considered as 1 migraine attack. If the onset of the migraine was prevented by a rescue drug, it should be considered as 1 migraine attack even if the aura had started.

  • Change From Baseline in Migraine Attacks (According to 24-Hour Rule) Over Week 19 to Week 22 Period [ Time Frame: Baseline (28 days before randomization), Week 19 to Week 22 Period ] [ Designated as safety issue: No ]
    The change from baseline in average number of migraine attacks (as per 24-hour rule) over Week 19 to Week 22 period was calculated by subtracting the baseline value from the average value of the Week 19 to Week 22 period.

  • Average Number of Rescue Drug Treatment Days [ Time Frame: Baseline (28 days before randomization) ] [ Designated as safety issue: No ]
    Rescue medications are administered to participants when efficacy of study drug is not satisfactory, or effect of study drug is too great and is likely to cause a hazard to participant, or to manage an emergency situation. If an aura of migraine, a migraine attack or a non-migraine headache attack occurred during the study period, use of following rescue drugs was permitted: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), ergotamines, triptans and anti-emetics (drug used to stop vomiting). Average at baseline was calculated by dividing total number of rescue drug treatment days until baseline by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).

  • Change From Baseline in the Average Number of Rescue Drug Treatment Days at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Rescue medications are medicines that may be administered to the participants when efficacy of study drug is not satisfactory, or the effect of study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. If an aura of migraine, a migraine attack or a non-migraine headache attack occurred during the study period, use of following rescue drugs was permitted: analgesics, NSAIDs, ergotamines, triptans and anti-emetics. Average at Month 6 was calculated by dividing total number of rescue drug treatment days until that month by the total number of days of assessment, multiplied by 28 (a month was equal to 28 days).

  • Percentage of Participants With Response to Study Treatment [ Time Frame: Month 1, 2, 3, 4, 5 and 6 ] [ Designated as safety issue: No ]
    Responders were the participants who had at least 50 percent reduction in the average number of monthly migraine attacks.

  • Short Form-36 Health Survey (SF-36) Score [ Time Frame: Baseline (28 days before randomization), Day 29, 85 and final evaluation (FE) (Day 155/early withdrawal [EW]) ] [ Designated as safety issue: No ]
    The SF-36 is a survey of participant health. It consists of 8 scaled scores, which are weighted sums of the questions in their section. The 8 sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. Each item is scored on a 0-100 range so that total score ranges from 0-100 with high score indicating more favorable health state. Final evaluation was done at Day 155 or at discontinuation for those participants who discontinued before Day 155.


Enrollment: 387
Study Start Date: April 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topiramate (JNS019) 50 mg
In titration period, topiramate 25 milligram (mg) tablet will be given once daily in evening orally for 7 days; then topiramate 25 mg tablet twice daily orally from Day 8 to Day 14; then topiramate 25 mg tablet twice daily along with matching placebo tablet once daily in the evening orally from Day 15 to Day 21; then topiramate 25 mg tablet along with matching placebo tablet twice daily orally from Day 22 to Day 28 and will be continued further for 18 weeks in the fixed dose period.
Drug: Topiramate
In the titration period, topiramate 25-mg tablet once daily orally for 1 week, the dose will be increased by 1 tablet every week up to twice daily for a total of 4 weeks so that the total daily dose given is 50 mg or 100mg. The dose given in the final titration week will be continued for further 18 weeks (fixed dose period).
Drug: Placebo
In the titration period, matching placebo tablet once daily orally for 1 week, the dose will be increased by 1 tablet every week up to twice daily for a total of 4 weeks. The dose given in the final titration week will be continued for further 18 weeks (fixed dose period).
Experimental: Topiramate 100 mg
In titration period, topiramate 25 mg tablet will be given once daily in the evening orally for 7 days; then topiramate 25 mg tablet twice daily orally from Day 8 to Day 14; then topiramate 25 mg tablet twice daily (1 tablet in the morning and 2 tablets in the evening) orally from Day 15 to Day 21; then 2 topiramate 25 mg tablets twice daily orally from Day 22 to Day 28 and will be continued further for 18 weeks in the fixed dose period.
Drug: Topiramate
In the titration period, topiramate 25-mg tablet once daily orally for 1 week, the dose will be increased by 1 tablet every week up to twice daily for a total of 4 weeks so that the total daily dose given is 50 mg or 100mg. The dose given in the final titration week will be continued for further 18 weeks (fixed dose period).
Placebo Comparator: Placebo
In titration period, matching placebo tablet will be given once daily in evening orally for 7 days; followed by matching placebo tablet twice daily orally from Day 8 to Day 14; followed by matching placebo tablet twice daily (1 tablet in the morning and 2 tablets in the evening) orally from Day 15 to Day 21; followed by 2 matching placebo tablets twice orally from Day 22 to Day 28 and will becontinued further for 18 weeks in the fixed dose period.
Drug: Placebo
In the titration period, matching placebo tablet once daily orally for 1 week, the dose will be increased by 1 tablet every week up to twice daily for a total of 4 weeks. The dose given in the final titration week will be continued for further 18 weeks (fixed dose period).

Detailed Description:

This study is a multicenter (more than 1 site), placebo-controlled (compared to placebo), randomized (participants assigned study drug by chance), double-blind (neither the participant nor the physician know the assigned study drug), parallel-group comparison (comparison for each group at the same time) study. The study period consists of 4 phases: the observation phase, double-blind phase, exit period and follow-up period. After the double-blind phase, the participants will be transferred to the continuous treatment study. The observation phase which is started after informed consent consists of the washout period (non-treatment period with migraine preventive medication: at least 2 weeks) and baseline determination period (at least 4 weeks). The participants who complete the observation phase and meet the inclusion criteria will be randomly assigned to the topiramate 50 milligram (mg) group, topiramate 100-mg group or placebo group after registration. The double-blind phase consists of the titration period (dose-escalation, 4 weeks) and fixed-dose period (18 weeks). In the titration period, starting from 1 topiramate 25-mg tablet or 1 topiramate 25-mg placebo tablet once daily (1 tablet in the evening), the dose will be increased by 1 tablet every week up to twice daily (2 tablets in the morning, 2 tablets in the evening). After that, the twice-daily treatment (2 tablets in the morning, 2 tablets in the evening) will be continued for 7 days from Day 22 to Day 28. In the fixed-dose period, the topiramate 25-mg tablets or topiramate 25-mg placebo tablets at the same dose as that in the final treatment in titration period will be continued. The participants who are not transferred to the continuous treatment study after completion of the double-blind phase or after discontinuation during the double-blind phase will be transferred to the exit period (up to 1 week).The participants who complete the exit period will be transferred to the follow-up period, and a follow-up of the participant's safety and headache symptoms such as the migraine period rate will be conducted for 4 weeks after the completion of investigational treatment. Meanwhile, the participants who complete the double-blind phase or those who discontinue the study at Week 4 or later in the fixed-dose period during the double-blind phase due to lack of efficacy and give consent to transfer to the continuous treatment study will be transferred to the transfer period (up to 3 weeks) under blind conditions.

  Eligibility

Ages Eligible for Study:   20 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants who meet the Second Edition of the International Classification of Headache Disorders (ICHD-II), 1.1 Migraine without aura or 1.2 Migraine with aura over at least 6 months before the time of informed consent
  • Participants who had an average of no more than 8 migraine attacks per month during 3 months before informed consent and an average of no more than 14 headache (migraine and non-migraine) days
  • Participants whose number of migraine attacks during the baseline determination period (28 days) is 3 to 12 according to the 24-hour rule and number of headache days (migraine and non-migraine) is no more than 14
  • Participants who took no migraine preventive medications over 2 weeks before informed consent, or who can take at least 2-week washout period before baseline determination period if they are taking migraine preventive medications
  • Female participants must be postmenopausal, surgically sterile, abstinent, or can take adequate contraceptive measures after informed consent and continue it to the completion of investigational treatment

Exclusion Criteria:

  • Participants who cannot distinguish between migraine and non-migraine headache
  • Participants with headache other than those described in the ICHD-II, 1.1 Migraine without aura, 1.2 Migraine with aura, 2. Tension headache or 11.5 Sinus headache
  • If the participant has received drug therapies for prevention of migraine, the discontinued preventive therapies due to insufficient efficacy should be at least three types
  • Participants who excessively took medications for migraine attacks such as analgesics (drug used to control pain) as medications to be taken as needed within 3 months before informed consent
  • Participants who have taken topiramate (test drug in this study) in the past
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01081795

Locations
Japan
Bunkyo, Japan
Chitose, Japan
Hachioji, Japan
Iruma, 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, Japan
Sapporo, Japan
Shimotsuga, Japan
Shinjuku, Japan
Shinjuku-Ku, Japan
Shizuoka, Japan
Suginami-Ku, Japan
Tokyo, Japan
Toyama, Japan
Toyonaka, Japan
Ube, Japan
Ube N/A, Japan
Yokohama, Japan
Yonago N/A, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01081795     History of Changes
Other Study ID Numbers: CR013681, JNS019-JPN-02
Study First Received: March 4, 2010
Results First Received: March 19, 2013
Last Updated: June 20, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Topiramate
Migraine

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Topiramate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on August 19, 2014