Trial Outcomes & Findings for An Efficacy and Tolerability Study of Topiramate in Participants With Migraine (NCT NCT01060111)

Last Updated: 2013-08-22

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

250 participants

Primary outcome timeframe

Maintenance period (Weeks 7 to 10)

Results posted on

2013-08-22

Participant Flow

Out of 250 consented participants, 243 participants were assigned to study treatment.

Participant milestones

Participant milestones
Measure	Topiramate Standard Topiramate 25 milligram (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.	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.	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.
Overall Study STARTED	81	84	80
Overall Study Treated	81	83	79
Overall Study COMPLETED	54	61	45
Overall Study NOT COMPLETED	27	23	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Topiramate Standard Topiramate 25 milligram (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.	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.	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.
Overall Study Adverse Event	9	5	18
Overall Study Lack of Efficacy	2	1	0
Overall Study Inappropriate participant	5	4	5
Overall Study Participants' evasion for hospital visit	0	3	2
Overall Study Participants' non-cooperation	1	0	0
Overall Study Adverse event and insufficient effect	0	1	0
Overall Study Other	2	3	4

Baseline Characteristics

An Efficacy and Tolerability Study of Topiramate in Participants With Migraine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Topiramate Standard n=81 Participants 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.	Topiramate Slow n=83 Participants 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.	Topiramate Slow and Propranolol Booster n=78 Participants 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.	Total n=242 Participants Total of all reporting groups
Age, Customized Age 20 and over but younger than age 30	16 Participants n=5 Participants	23 Participants n=7 Participants	22 Participants n=5 Participants	61 Participants n=4 Participants
Age, Customized Age 30 and over but younger than age 40	24 Participants n=5 Participants	27 Participants n=7 Participants	30 Participants n=5 Participants	81 Participants n=4 Participants
Age, Customized Age 40 and over but younger than age 50	22 Participants n=5 Participants	19 Participants n=7 Participants	16 Participants n=5 Participants	57 Participants n=4 Participants
Age, Customized Age 50 and over but younger than age 60	11 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	29 Participants n=4 Participants
Age, Customized Age 60 and over	7 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Female	72 Participants n=5 Participants	76 Participants n=7 Participants	63 Participants n=5 Participants	211 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants	31 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate Standard n=51 Participants 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.	Topiramate Slow n=57 Participants 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.	Topiramate Slow and Propranolol Booster n=43 Participants 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.
Percentage Decrease in Migraine Episodes	48 Percentage decrease in migraine episodes Standard Deviation 69	57 Percentage decrease in migraine episodes Standard Deviation 48	46 Percentage decrease in migraine episodes Standard Deviation 69

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Topiramate Standard n=81 Participants 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.	Topiramate Slow n=83 Participants 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.	Topiramate Slow and Propranolol Booster n=78 Participants 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.
Change From Baseline in Migraine Frequency at Week 6 Baseline	1.48 Migraine episodes/Week Standard Deviation 0.76	1.58 Migraine episodes/Week Standard Deviation 0.80	1.59 Migraine episodes/Week Standard Deviation 0.87
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	0.89 Migraine episodes/Week Standard Deviation 0.88	0.74 Migraine episodes/Week Standard Deviation 1.31

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate Standard n=81 Participants 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.	Topiramate Slow n=83 Participants 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.	Topiramate Slow and Propranolol Booster n=78 Participants 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.
Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6 Baseline	1.32 Units on a scale Standard Deviation 1.26	1.29 Units on a scale Standard Deviation 1.14	1.42 Units on a scale Standard Deviation 1.77
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	0.99 Units on a scale Standard Deviation 1.08	0.95 Units on a scale Standard Deviation 2.00

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Topiramate Standard n=81 Participants 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.	Topiramate Slow n=82 Participants 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.	Topiramate Slow and Propranolol Booster n=76 Participants 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.
Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6 Baseline	5.83 Units on a Scale Standard Deviation 1.55	5.68 Units on a Scale Standard Deviation 1.68	5.51 Units on a Scale Standard Deviation 1.78
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	2.45 Units on a Scale Standard Deviation 2.84	2.31 Units on a Scale Standard Deviation 2.32

Adverse Events

Topiramate Standard

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

Topiramate Slow

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

Topiramate Slow and Propranolol Booster

Serious events: 0 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Clinical Research Associate

Medical Affairs / Janssen-Cil Korea

Phone: 82-2-2094-4837

Results disclosure agreements

Principal investigator is a sponsor employee PI cannot provide any trial related information to external parties' without mutual agreement with the Sponsor. This is valid even after the contract is cancelled.
Publication restrictions are in place

Restriction type: OTHER

Measure	Topiramate Standard n=81 participants at risk 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.	Topiramate Slow n=83 participants at risk 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.	Topiramate Slow and Propranolol Booster n=79 participants at risk 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.
Nervous system disorders Paresthesia	51.9% 42/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	57.8% 48/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	45.6% 36/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Nervous system disorders Dizziness	6.2% 5/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	10.8% 9/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	17.7% 14/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Nervous system disorders Paraesthesia	7.4% 6/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.0% 5/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	3.8% 3/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Nervous system disorders Somnolence	3.7% 3/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	3.6% 3/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	8.9% 7/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Gastrointestinal disorders Gastrointestinal disorder	7.4% 6/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.0% 5/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	13.9% 11/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Gastrointestinal disorders Nausea	1.2% 1/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	2.4% 2/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.3% 5/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Investigations Weight decreased	17.3% 14/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	8.4% 7/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	11.4% 9/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
General disorders Fatigue	3.7% 3/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.0% 5/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	5.1% 4/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
General disorders Feeling abnormal	2.5% 2/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.0% 5/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	0.00% 0/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Metabolism and nutrition disorders Anorexia	6.2% 5/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	3.6% 3/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	10.1% 8/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Psychiatric disorders Psychomotor retardation	1.2% 1/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	3.6% 3/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	10.1% 8/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Psychiatric disorders Depression	6.2% 5/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	0.00% 0/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	0.00% 0/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Nervous system disorders Headache	8.6% 7/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	6.0% 5/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	3.8% 3/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Gastrointestinal disorders Dyspepsia	4.9% 4/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	0.00% 0/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	1.3% 1/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
Psychiatric disorders Insomnia	4.9% 4/81 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	2.4% 2/83 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.	1.3% 1/79 • Baseline up to Week 10 Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.