Migraine Disorders
Conditions
Brief summary
This study will evaluate the efficacy, safety and tolerability of prophylactic (preventative) treatment with BOTOX® (onabotulinumtoxinA) compared to topiramate in adults with chronic migraine.
Interventions
BIOLOGICALonabotulinumtoxinA
155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks.
DRUGTopiramate
Topiramate up to a maximum oral dose of 100 mg/day.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* History of chronic migraine * More than 15 headache days in a 28 day period (headaches that last more than 4 hours and/or require treatment with prescription medication).
Exclusion criteria
* Taking opioid-containing products for acute headache treatment more than 8 days during a 28-day period * Previous treatment with botulinum toxin of any serotype for any reason * Previous treatment with topiramate * On a ketogenic diet (high in fat, low in carbohydrates) * History of acute myopia or increased intraocular pressure * Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis or any other significant disease that might interfere with neuromuscular function * Acupuncture, transcutaneous electrical stimulation (TENS), cranial traction, dental splints for headache, or injection of anesthetics/steroids in the 4 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 50% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Frequency of Headache Days Per 28-day Period | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. A negative change from Baseline (less headache days) indicates improvement. |
| Change From Baseline in Headache Impact Test (HIT-6) Total Score | Baseline (Day 1) to the last 28-day period ending with Week 30 | The HIT-6 is a valid disease-targeted measure used to assess the impact of headaches, comprised of 6 items that assess pain, role functioning, social functioning, cognitive functioning, vitality, and psychological distress. A total score is created by summingacross all items, and ranges from 36 (no impact) to 78 (severe impact) reflecting a best to worst scoring. A negative change from Baseline (a lower score) indicates improvement. |
| Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days | Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32 | Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 70% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOTOX® 155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks for up to 3 treatments. | 140 |
| Topiramate Topiramate starting at a daily oral dose of 25 mg/day titrated up to a maximum dose of 100 mg/day for 36 weeks. Participants who discontinue topiramate are eligible to receive treatment with BOTOX®. | 142 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment 1 | Multiple Reasons Specified | 27 | 58 |
| Treatment 2 | Multiple Reasons Specified | 0 | 25 |
Baseline characteristics
| Characteristic | Topiramate | BOTOX® | Total |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 12.6 | 40.2 years STANDARD_DEVIATION 11.7 | 39.8 years STANDARD_DEVIATION 12.1 |
| Age, Customized 18 to <25 | 21 Participants | 16 Participants | 37 Participants |
| Age, Customized 25 to <35 | 40 Participants | 30 Participants | 70 Participants |
| Age, Customized 35 to <45 | 29 Participants | 43 Participants | 72 Participants |
| Age, Customized 45 to <55 | 34 Participants | 33 Participants | 67 Participants |
| Age, Customized ≥55 | 18 Participants | 18 Participants | 36 Participants |
| Body Mass Index (BMI | 28.8 kg/m^2 STANDARD_DEVIATION 6.5 | 28.9 kg/m^2 STANDARD_DEVIATION 7.1 | 28.8 kg/m^2 STANDARD_DEVIATION 6.8 |
| Height | 167.0 centimeter (cm) STANDARD_DEVIATION 8.7 | 167.4 centimeter (cm) STANDARD_DEVIATION 8.5 | 167.2 centimeter (cm) STANDARD_DEVIATION 8.5 |
| Race/Ethnicity, Customized Asian | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 8 Participants | 13 Participants | 21 Participants |
| Race/Ethnicity, Customized Hispanic | 12 Participants | 11 Participants | 23 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 118 Participants | 111 Participants | 229 Participants |
| Sex: Female, Male Female | 122 Participants | 117 Participants | 239 Participants |
| Sex: Female, Male Male | 20 Participants | 23 Participants | 43 Participants |
| Use of Headache Prophylactic Treatment(s) | 25 Participants | 26 Participants | 51 Participants |
| Weight | 80.5 kilogram (kg) STANDARD_DEVIATION 20.6 | 81.0 kilogram (kg) STANDARD_DEVIATION 21.8 | 80.8 kilogram (kg) STANDARD_DEVIATION 21.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 220 | 0 / 142 |
| other Total, other adverse events | 27 / 220 | 89 / 142 |
| serious Total, serious adverse events | 4 / 220 | 6 / 142 |
Outcome results
Primary
Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days
Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 50% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.
Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Population: ITT Set included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® | Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days | 40.0 percentage of participants |
| Topiramate | Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days | 12.0 percentage of participants |
p-value: <0.00195% CI: [2.681, 9.085]Regression, Logistic
Secondary
Change From Baseline in Headache Impact Test (HIT-6) Total Score
The HIT-6 is a valid disease-targeted measure used to assess the impact of headaches, comprised of 6 items that assess pain, role functioning, social functioning, cognitive functioning, vitality, and psychological distress. A total score is created by summingacross all items, and ranges from 36 (no impact) to 78 (severe impact) reflecting a best to worst scoring. A negative change from Baseline (a lower score) indicates improvement.
Time frame: Baseline (Day 1) to the last 28-day period ending with Week 30
Population: Participants from the ITT Set, all randomized participants, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® | Change From Baseline in Headache Impact Test (HIT-6) Total Score | -5.6 score on a scale | Standard Deviation 7.2 |
| Topiramate | Change From Baseline in Headache Impact Test (HIT-6) Total Score | -1.3 score on a scale | Standard Deviation 3.9 |
p-value: <0.00195% CI: [-5.766, -2.731]ANCOVA
Secondary
Change From Baseline in the Frequency of Headache Days Per 28-day Period
Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. A negative change from Baseline (less headache days) indicates improvement.
Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Population: ITT Set included all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX® | Change From Baseline in the Frequency of Headache Days Per 28-day Period | -8.3 days | Standard Deviation 8.9 |
| Topiramate | Change From Baseline in the Frequency of Headache Days Per 28-day Period | -2.1 days | Standard Deviation 5.6 |
p-value: <0.00195% CI: [-7.936, -4.462]ANCOVA
Secondary
Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days
Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 70% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.
Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Population: ITT Set included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BOTOX® | Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days | 27.1 percentage of participants |
| Topiramate | Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days | 8.5 percentage of participants |
p-value: <0.00195% CI: [2.014, 8.157]Regression, Logistic