An Efficacy and Tolerability Study of Topiramate in Participants With Migraine

Adequate Therapy of Topiramate in Migraine

The purpose of this study is to investigate the adequacy (reasonably good) of topiramate therapy (medicine or medical care given to a participant for a disease or condition) in prevention of migraine (type of severe headache that occurs periodically and is often associated with nausea, vomiting, and constipation or diarrhea) by comparing standard titration (slow increase in drug dosage, guided by patient's responses) therapy to slow titration therapy and slow titration therapy boosted by the concurrent use of propranolol in participants with migraine with or without aura (having to do with the ear) for more than or equal to 2 attacks per month.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Topiramate Standard; Drug: Topiramate Slow; Drug: Propranolol booster

Detailed Description

This is a prospective (study following participants forward in time), single-blind (Physician does not know the intervention), randomized (study drug assigned by chance) and comparative multi-center (conducted in more than 1 center) study to assess appropriate administration methods with topiramate preventive therapy in participants with migraine. The study consists of 3 periods: Screening period (4 weeks), Treatment period consisting of 2 titration periods (3 weeks each) and Maintenance period (4 weeks). During Screening period, after the diagnosis of participants' headache, symptoms and severity of migraine will be investigated through a headache diary and participants will be selected for treatment period. In the treatment period, the selected participants will be randomly assigned to either of the 3 topiramate therapy: 'topiramate standard group', 'topiramate slow group', and 'topiramate slow plus propranolol (booster) group'. In the 'topiramate standard group' - participants will receive an initial dose of topiramate 25 milligram (mg) once daily and the dose of topiramate will be increased by 25 mg per day at an interval of 1-week up to the target dose of 50 mg to 100 mg up to Week 6; and a maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion. In 'topiramate slow group' - participants will start with an initial dose of 25 mg once daily and the dose will be increased by 25 mg per day at an interval of 2-weeks up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion. In 'topiramate slow plus propranolol (booster) group' - participants will follow the same dosage regimen as in the 'topiramate slow group' along with concurrent administration of booster dose of propranolol 80 mg once daily (40 mg each time in the morning and in the evening) for 6 weeks. The participants will primarily be evaluated for reduction in migraine frequency between Week 7 and 10 using a headache diary questionnaire maintained by them. Participants' quality of life will be assessed using Migraine Disability Assessment (MIDAS) score and intensity of pain in migraine will be assessed using Visual Analogue Scale (VAS). Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
  • Daegu, Korea, Republic of
  • Kwangjoo, Korea, Republic of
  • Kyunggi-Do, Korea, Republic of
  • Seoul, Korea, Republic of
  • Uijeongbu, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Particpants who have signed the consent form
• Participants who have 3 to 14 episodes of migraine a month
• Participants whose duration of migraine is at least 6 months
• Participants who can read and understand the migraine disability assessment (MIDAS) questionnaire
• Female Participants who are using an appropriate contraception method or have negative pregnancy test results

Exclusion Criteria:

• Participants whose headache attacks at Baseline or during the study period are assumed to be caused by a drug withdrawal syndrome
• Participants whose migraine has appeared first at over 50 years of age
• Participants who have taken anticonvulsants (valproic acid, gabapentin), beta adrenergic blockers (propranolol) and calcium antagonists (sibelium, verapamil, diltiazem) or topiramate or propranolol within the last 8 weeks
• Participants with progressive neurological (pertaining to the nervous system) disorder
• Participants with severe renal (pertaining to the kidneys) disorder, hepatic (pertaining to the liver) failure or diabetes (disorder in which there is decreased insulin in the body or the body's insulin is not effective, resulting in high blood sugar, increased thirst and urine, and many other side effects) or with the history of renal calculus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topiramate Standard; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 1-week up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion.	Drug: Topiramate Standard; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 1-week up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion.
Experimental: Topiramate Slow; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 2-weeks up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion.	Drug: Topiramate Slow; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 2-weeks up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion.
Experimental: Topiramate Slow and Propranolol Booster; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 2-weeks up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion. Propranolol 80 mg will be administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.	Drug: Topiramate Slow; Topiramate 25 mg will be administered once daily and the dose will be increased by 25 mg per day at an interval of 2-weeks up to a dose of 50 mg to 100 mg up to Week 6. A maintenance dose of 50 mg to 100 mg will be administered twice daily up to Week 10 as per Physician's discretion.; Drug: Propranolol booster; Propranolol 80 mg will be administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Decrease in Migraine Episodes	Decrease in percentage of migraine frequency (episodes) was measured from baseline using a headache diary which is a typical scale measuring neuropsychiatric symptoms in a migraine participant. Migraine will be diagnosed in accordance with the guidelines of the International Headache Society (IHS).	Maintenance period (Weeks 7 to 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Migraine Frequency at Week 6	The migraine frequency at Week 6 was evaluated through a headache diary completed by a participant and the reduction rate of migraine frequency compared to the Baseline period was measured. Change values were calculated as Baseline value minus value at Week 6.	Baseline and Week 6
Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6	MIDAS scoring ranges from 0 to 63. The scores are divided into ranges of disability with higher scores indicating increased disability as follows: 0-5 (Grade I - Minimal or infrequent disability); 6-10 (Grade II - Mild or infrequent disability); 11-20 (Grade III - Moderate disability); and 21+ (Grade IV - Severe disability). Change values were calculated as Baseline value minus value at Week 6.	Baseline and Week 6
Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6	VAS was used to measure the intensity of migraine. The assessment scale ranges from 0 to 10. One end of the line drawn on the questionnaire is marked with 0 point indicating "no headache" and the other end with 10 points indicating "unimaginably strong headache." It means that the higher the score, the severe the pain is. Change values were calculated as Baseline value minus value at Week 6.	Baseline and Week 6

Collaborators and Investigators

• Sponsor: Janssen Korea, Ltd., Korea

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: January 29, 2010
• First Submitted That Met QC Criteria: January 29, 2010
• First Posted (Estimate): February 2, 2010

Study Record Updates

• Last Update Posted (Estimate): August 22, 2013
• Last Update Submitted That Met QC Criteria: August 14, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Migraine; Propranolol; Topiramate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anticonvulsants; Propranolol; Topiramate
• Other Study ID Numbers: CR011944; MIG-KOR-001