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An Efficacy and Tolerability Study of Topiramate in Participants With Migraine

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ClinicalTrials.gov Identifier: NCT01060111
Recruitment Status : Completed
First Posted : February 2, 2010
Results First Posted : August 6, 2013
Last Update Posted : August 22, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: Topiramate Standard
Drug: Topiramate Slow
Drug: Propranolol booster
Enrollment 250
Recruitment Details  
Pre-assignment Details Out of 250 consented participants, 243 participants were assigned to study treatment.
Arm/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description 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 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 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.
Period Title: Overall Study
Started 81 84 80
Treated 81 83 79
Completed 54 61 45
Not Completed 27 23 35
Reason Not Completed
Adverse Event             9             5             18
Lack of Efficacy             2             1             0
Inappropriate participant             5             4             5
Participants' evasion for hospital visit             0             3             2
Participants' non-cooperation             8             6             6
Adverse event and insufficient effect             0             1             0
Participants' non-cooperation             1             0             0
Other             2             3             4
Arm/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster Total
Hide Arm/Group Description 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 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 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 of all reporting groups
Overall Number of Baseline Participants 81 83 78 242
Hide Baseline Analysis Population Description
Baseline characteristics were measured for Intent-to-treat (ITT) population which was defined as participants who took topiramate at least once and had migraine improvement data at the Week 6.
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 83 participants 78 participants 242 participants
Age 20 and over but younger than age 30 16 23 22 61
Age 30 and over but younger than age 40 24 27 30 81
Age 40 and over but younger than age 50 22 19 16 57
Age 50 and over but younger than age 60 11 11 7 29
Age 60 and over 7 2 2 11
[1]
Measure Description: Age, Customized was measured for ITT population which was defined as participants who took topiramate at least once and had migraine improvement data at the Week 6. Here 'N=239' (80, 82, and 78 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively) signifies the participants who were evaluated for this Baseline characteristic.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 83 participants 78 participants 242 participants
Female
72
  88.9%
76
  91.6%
63
  80.8%
211
  87.2%
Male
9
  11.1%
7
   8.4%
15
  19.2%
31
  12.8%
[1]
Measure Description: Gender was measured for ITT population which was defined as participants who took topiramate at least once and had migraine improvement data at the Week 6.
1.Primary Outcome
Title Percentage Decrease in Migraine Episodes
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description:
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 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 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 Number of Participants Analyzed 51 57 43
Mean (Standard Deviation)
Unit of Measure: Percentage decrease in migraine episodes
48  (69) 57  (48) 46  (69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Standard, Topiramate Slow, Topiramate Slow and Propranolol Booster
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6207
Comments [Not Specified]
Method ANOVA
Comments Analysis of Variance (ANOVA) for treatment groups (Topiramate standard, Topiramate slow, Topiramate slow and Propranolol booster) was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Topiramate Standard, Topiramate Slow and Propranolol Booster
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferioirity was to be concluded if the ratio of percentage decrease in migraine episodes was greater than 0.7. Power of calculation was 0.9, significance level was 0.025.
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of percentage decrease
Estimated Value 0.950
Confidence Interval (2-Sided) 95%
0.519 to 1.737
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Migraine Frequency at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description:
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every Week till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion. Propranolol 80 mg administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.
Overall Number of Participants Analyzed 81 83 78
Mean (Standard Deviation)
Unit of Measure: Migraine episodes/Week
Baseline 1.48  (0.76) 1.58  (0.80) 1.59  (0.87)
Change at Week 6 (n=51, 57, 43) 0.89  (1.04) 0.89  (0.88) 0.74  (1.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Standard, Topiramate Slow, Topiramate Slow and Propranolol Booster
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7247
Comments [Not Specified]
Method ANOVA
Comments Analysis of Variance (ANOVA) for treatment groups (Topiramate standard, Topiramate slow, Topiramate slow and Propranolol booster) was used.
3.Secondary Outcome
Title Change From Baseline in Migraine Disability Assessment (MIDAS) Score at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description:
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every Week till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion. Propranolol 80 mg administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.
Overall Number of Participants Analyzed 81 83 78
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline 1.32  (1.26) 1.29  (1.14) 1.42  (1.77)
Change at Week 6 (n=54, 61, 44) 0.99  (1.18) 0.99  (1.08) 0.95  (2.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Standard, Topiramate Slow, Topiramate Slow and Propranolol Booster
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9872
Comments [Not Specified]
Method ANOVA
Comments Analysis of Variance (ANOVA) for treatment groups (Topiramate standard, Topiramate slow, Topiramate slow and Propranolol booster) was used.
4.Secondary Outcome
Title Change From Baseline in Visual Analogue Scale (VAS) Score at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description:
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every Week till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion.
Topiramate Capsule 25 mg administered once daily till week 1. From Week 2 dose was increased by 25 mg every 2 Weeks till a dose of 50 mg to 100 mg up to Week 6 and a dose of 50 mg to 100 mg twice daily up to Week 10 as per Physician's discretion. Propranolol 80 mg administered once daily, 40 mg in the morning and 40 mg in the evening up to Week 6.
Overall Number of Participants Analyzed 81 82 76
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline 5.83  (1.55) 5.68  (1.68) 5.51  (1.78)
Change at Week 6 (n= 53, 59, 42) 1.83  (2.54) 2.45  (2.84) 2.31  (2.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Topiramate Standard, Topiramate Slow, Topiramate Slow and Propranolol Booster
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4326
Comments Analysis of Variance (ANOVA) for treatment groups (Topiramate standard, Topiramate slow, Topiramate slow and Propranolol booster) was used.
Method ANOVA
Comments [Not Specified]
Time Frame Baseline up to Week 10
Adverse Event Reporting Description Participants evaluable for safety were 81, 83, and 79 for topiramate standard, topiramate slow, topiramate slow and propranolol booster groups respectively.
 
Arm/Group Title Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Hide Arm/Group Description 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 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 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.
All-Cause Mortality
Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/81 (0.00%)   0/83 (0.00%)   0/79 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Topiramate Standard Topiramate Slow Topiramate Slow and Propranolol Booster
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   62/81 (76.54%)   62/83 (74.70%)   54/79 (68.35%) 
Gastrointestinal disorders       
Gastrointestinal disorder * 1  6/81 (7.41%)  5/83 (6.02%)  11/79 (13.92%) 
Nausea * 1  1/81 (1.23%)  2/83 (2.41%)  5/79 (6.33%) 
Dyspepsia * 1  4/81 (4.94%)  0/83 (0.00%)  1/79 (1.27%) 
General disorders       
Fatigue * 1  3/81 (3.70%)  5/83 (6.02%)  4/79 (5.06%) 
Feeling abnormal * 1  2/81 (2.47%)  5/83 (6.02%)  0/79 (0.00%) 
Investigations       
Weight decreased * 1  14/81 (17.28%)  7/83 (8.43%)  9/79 (11.39%) 
Metabolism and nutrition disorders       
Anorexia * 1  5/81 (6.17%)  3/83 (3.61%)  8/79 (10.13%) 
Nervous system disorders       
Paresthesia * 1  42/81 (51.85%)  48/83 (57.83%)  36/79 (45.57%) 
Dizziness * 1  5/81 (6.17%)  9/83 (10.84%)  14/79 (17.72%) 
Paraesthesia * 1  6/81 (7.41%)  5/83 (6.02%)  3/79 (3.80%) 
Somnolence * 1  3/81 (3.70%)  3/83 (3.61%)  7/79 (8.86%) 
Headache * 1  7/81 (8.64%)  5/83 (6.02%)  3/79 (3.80%) 
Psychiatric disorders       
Psychomotor retardation * 1  1/81 (1.23%)  3/83 (3.61%)  8/79 (10.13%) 
Depression * 1  5/81 (6.17%)  0/83 (0.00%)  0/79 (0.00%) 
Insomnia * 1  4/81 (4.94%)  2/83 (2.41%)  1/79 (1.27%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Clinical Research Associate
Organization: Medical Affairs / Janssen-Cil Korea
Phone: 82-2-2094-4837
Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01060111     History of Changes
Other Study ID Numbers: CR011944
MIG-KOR-001
First Submitted: January 29, 2010
First Posted: February 2, 2010
Results First Submitted: March 26, 2013
Results First Posted: August 6, 2013
Last Update Posted: August 22, 2013