Migraine
Conditions
Keywords
Migraine, Topiramate, Propranolol
Brief summary
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.
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.
Interventions
DRUGTopiramate 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.
DRUGTopiramate 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.
DRUGPropranolol booster
Propranolol 80 mg will be administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.
Sponsors
Janssen Korea, Ltd., Korea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Decrease in Migraine Episodes | Maintenance period (Weeks 7 to 10) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Migraine Frequency at Week 6 | Baseline and 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. |
| Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Baseline and 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. |
| Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Baseline and 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. |
Countries
South Korea
Participant flow
Pre-assignment details
Out of 250 consented participants, 243 participants were assigned to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Standard Topiramate 25 mg was administered once daily and the dose was 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 was administered twice daily up to Week 10 as per Physician's discretion. | 81 |
| Topiramate Slow Topiramate 25 mg was administered once daily and the dose was 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 was administered twice daily up to Week 10 as per Physician's discretion. | 83 |
| Topiramate Slow and Propranolol Booster Topiramate 25 mg was administered once daily and the dose was 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 was administered twice daily up to Week 10 as per Physician's discretion. Propranolol 80 mg was administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6. | 78 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 5 | 18 |
| Overall Study | Adverse event and insufficient effect | 0 | 1 | 0 |
| Overall Study | Inappropriate participant | 5 | 4 | 5 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Other | 2 | 3 | 4 |
| Overall Study | Participants' evasion for hospital visit | 0 | 3 | 2 |
| Overall Study | Participants' non-cooperation | 8 | 6 | 6 |
Baseline characteristics
| Characteristic | Topiramate Standard | Topiramate Slow | Topiramate Slow and Propranolol Booster | Total |
|---|---|---|---|---|
| Age, Customized Age 20 and over but younger than age 30 | 16 Participants | 23 Participants | 22 Participants | 61 Participants |
| Age, Customized Age 30 and over but younger than age 40 | 24 Participants | 27 Participants | 30 Participants | 81 Participants |
| Age, Customized Age 40 and over but younger than age 50 | 22 Participants | 19 Participants | 16 Participants | 57 Participants |
| Age, Customized Age 50 and over but younger than age 60 | 11 Participants | 11 Participants | 7 Participants | 29 Participants |
| Age, Customized Age 60 and over | 7 Participants | 2 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Female | 72 Participants | 76 Participants | 63 Participants | 211 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 81 | 62 / 83 | 54 / 79 |
| serious Total, serious adverse events | 0 / 81 | 0 / 83 | 0 / 79 |
Outcome results
Primary
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).
Time frame: Maintenance period (Weeks 7 to 10)
Population: The intent-to-treat (ITT) population included all the participants who took topiramate at least once and had migraine improvement data at the Week 6. Here 'N' signifies participants who were evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate Standard | Percentage Decrease in Migraine Episodes | 48 Percentage decrease in migraine episodes | Standard Deviation 69 |
| Topiramate Slow | Percentage Decrease in Migraine Episodes | 57 Percentage decrease in migraine episodes | Standard Deviation 48 |
| Topiramate Slow and Propranolol Booster | Percentage Decrease in Migraine Episodes | 46 Percentage decrease in migraine episodes | Standard Deviation 69 |
p-value: 0.6207ANOVA
p-value: 0.595% CI: [0.519, 1.737]t-test, 1 sided
Secondary
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.
Time frame: Baseline and Week 6
Population: The ITT population included all the participants who took topiramate at least once and had migraine improvement data at the Week 6. Here 'n' signifies participants evaluable for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Standard | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Baseline | 1.32 Units on a scale | Standard Deviation 1.26 |
| Topiramate Standard | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Change at Week 6 (n=54, 61, 44) | 0.99 Units on a scale | Standard Deviation 1.18 |
| Topiramate Slow | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Baseline | 1.29 Units on a scale | Standard Deviation 1.14 |
| Topiramate Slow | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Change at Week 6 (n=54, 61, 44) | 0.99 Units on a scale | Standard Deviation 1.08 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Baseline | 1.42 Units on a scale | Standard Deviation 1.77 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 | Change at Week 6 (n=54, 61, 44) | 0.95 Units on a scale | Standard Deviation 2 |
p-value: 0.9872ANOVA
Secondary
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.
Time frame: Baseline and Week 6
Population: The ITT population included all the participants who took topiramate at least once and had migraine improvement data at the Week 6. Here 'n' signifies participants evaluable for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Standard | Change From Baseline in Migraine Frequency at Week 6 | Baseline | 1.48 Migraine episodes/Week | Standard Deviation 0.76 |
| Topiramate Standard | Change From Baseline in Migraine Frequency at Week 6 | Change at Week 6 (n=51, 57, 43) | 0.89 Migraine episodes/Week | Standard Deviation 1.04 |
| Topiramate Slow | Change From Baseline in Migraine Frequency at Week 6 | Baseline | 1.58 Migraine episodes/Week | Standard Deviation 0.8 |
| Topiramate Slow | Change From Baseline in Migraine Frequency at Week 6 | Change at Week 6 (n=51, 57, 43) | 0.89 Migraine episodes/Week | Standard Deviation 0.88 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Migraine Frequency at Week 6 | Baseline | 1.59 Migraine episodes/Week | Standard Deviation 0.87 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Migraine Frequency at Week 6 | Change at Week 6 (n=51, 57, 43) | 0.74 Migraine episodes/Week | Standard Deviation 1.31 |
p-value: 0.7247ANOVA
Secondary
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.
Time frame: Baseline and Week 6
Population: The ITT population included all the participants who took topiramate at least once and had migraine improvement data at the Week 6. Here 'n' signifies participants evaluable for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topiramate Standard | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Baseline | 5.83 Units on a Scale | Standard Deviation 1.55 |
| Topiramate Standard | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Change at Week 6 (n= 53, 59, 42) | 1.83 Units on a Scale | Standard Deviation 2.54 |
| Topiramate Slow | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Baseline | 5.68 Units on a Scale | Standard Deviation 1.68 |
| Topiramate Slow | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Change at Week 6 (n= 53, 59, 42) | 2.45 Units on a Scale | Standard Deviation 2.84 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Baseline | 5.51 Units on a Scale | Standard Deviation 1.78 |
| Topiramate Slow and Propranolol Booster | Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 | Change at Week 6 (n= 53, 59, 42) | 2.31 Units on a Scale | Standard Deviation 2.32 |
p-value: 0.4326ANOVA