Migraine Disorders
Conditions
Brief summary
This is a 60 week study including a double-blind phase followed by an open-label phase.
Interventions
BIOLOGICALBotulinum Toxin Type A
Two treatment sessions in the double-blind phase and three treatment sessions in the open-label phase. Total minimum dose is 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas with the total maximum dose of 195 U with 39 head/neck injections.
OTHERplacebo (saline)
Two treatment sessions in the double-blind phase. Total minimum dose in 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas and the total maximum dose is 195 U with 39 head/neck injections.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Frequent migraine (\>=15 headache days per month) * \>=4 distinct headache episodes lasting \>=4 hours * \>=50% of baseline headache days migraine/probable migraine days
Exclusion criteria
* Previous use of botulinum toxin of any serotype or immunization to any botulinum toxin serotype * Any medical condition that puts the patient at increased risk with exposure to BOTOX * Diagnosis of complicated migraine, chronic tension-type headache, hypnic headache, hemicrania continua, new daily persistent headache * Use of prophylactic headache medication within 28 days prior to week -4 * Unremitting headache lasting continuously throughout the 4-week baseline period * Known or suspected TMD * Diagnosis of fibromyalgia * Beck depression inventory score \>24 at week-4 * Psychiatric problems that may have interfered with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Frequency of Headache Days | Baseline, Week 24 | Mean change from baseline in frequency (number) of headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day \[00:00 to 23:59\] for which the patient reported \>= 4 continuous hours of headache. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Cumulative Hours of Headache Occurring on Headache Days | Baseline, Week 24 | Mean change from baseline in total cumulative hours of headache occurring on headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day \[00:00 to 23:59\] when the patient reported \>= 4 continuous hours of headache. |
| Change in Frequency of Moderate/Severe Headache Days | Baseline, Week 24 | Mean change from baseline in frequency (number) of moderate/severe headache days during the 28 day period ending with Week 24. Those calendar days with \>= 4 continuous hours of headache were selected. As per the patient diary, all headache episodes occurring during those days with a maximum severity of moderate or severe were counted. |
| Change in Frequency of Migraine/Probable Migraine Headache Days | Baseline, Week 24 | Mean change from baseline in frequency (number) of migraine/probable migraine headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day with \>= 4 continuous hours of headache meeting the ICHD-II criteria for migraine or probable migraine. |
| Change in Frequency of Headache Episodes | Baseline, Week 24 | Mean change from baseline in frequency (number) of headache episodes during the 28 day period ending with Week 24. Headache episode defined as patient-reported headache with a start and stop time indicating that the pain lasted \>= 4 continuous hours. |
| Percentage of Patients With Severe HIT-6 Impact Category Scores | Week 24 | Percentage of patients with a severe (60-78) score on the Headache Impact Test (HIT-6) Questionnaire during the 28 day period, ending with Week 24. The HIT-6 consisted of 6 questions about headache and impact on the patient's health and well-being. Answers for each question ranged from 6=Never, 8=Rarely, 10=Sometimes, 11=Very Often, and 13=Always. The total scores ranged from 36-49 (Little or No Impact), 50-55 (Some Impact), 56-59 (Substantial Impact) and 60-78 (Severe Impact). |
Countries
Canada, Croatia, Germany, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A Two treatment sessions in the double-blind phase and three treatment sessions in the open-label extension phase. Total minimum dose is 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas with the total maximum dose of 195 U with 39 head/neck injections. | 347 |
| Placebo (Saline) Two treatment sessions in the double-blind phase. Total minimum dose in 155 U with 31 fixed-site, fixed dose injections across seven specific head/neck muscle areas and the total maximum dose is 195 U with 39 head/neck injections. | 358 |
| Total | 705 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A | Placebo (Saline) | Total |
|---|---|---|---|
| Age, Customized < 40 years | 149 participants | 160 participants | 309 participants |
| Age, Customized >= 40 years | 198 participants | 198 participants | 396 participants |
| Sex: Female, Male Female | 299 Participants | 303 Participants | 602 Participants |
| Sex: Female, Male Male | 48 Participants | 55 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 195 / 676 | 34 / 358 |
| serious Total, serious adverse events | 33 / 676 | 8 / 358 |
Outcome results
Primary
Change in Frequency of Headache Days
Mean change from baseline in frequency (number) of headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day \[00:00 to 23:59\] for which the patient reported \>= 4 continuous hours of headache.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Frequency of Headache Days | Baseline | 19.9 Headache Days | Standard Deviation 3.63 |
| Botulinum Toxin Type A | Change in Frequency of Headache Days | Change from Baseline at Week 24 | -9.0 Headache Days | Standard Deviation 6.54 |
| Placebo (Saline) | Change in Frequency of Headache Days | Baseline | 19.7 Headache Days | Standard Deviation 3.65 |
| Placebo (Saline) | Change in Frequency of Headache Days | Change from Baseline at Week 24 | -6.7 Headache Days | Standard Deviation 6.67 |
Secondary
Change in Frequency of Headache Episodes
Mean change from baseline in frequency (number) of headache episodes during the 28 day period ending with Week 24. Headache episode defined as patient-reported headache with a start and stop time indicating that the pain lasted \>= 4 continuous hours.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Frequency of Headache Episodes | Baseline | 12.0 Headache Episodes | Standard Deviation 5.27 |
| Botulinum Toxin Type A | Change in Frequency of Headache Episodes | Change from Baseline at Week 24 | -5.3 Headache Episodes | Standard Deviation 5.12 |
| Placebo (Saline) | Change in Frequency of Headache Episodes | Baseline | 12.7 Headache Episodes | Standard Deviation 5.29 |
| Placebo (Saline) | Change in Frequency of Headache Episodes | Change from Baseline at Week 24 | -4.6 Headache Episodes | Standard Deviation 4.84 |
Secondary
Change in Frequency of Migraine/Probable Migraine Headache Days
Mean change from baseline in frequency (number) of migraine/probable migraine headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day with \>= 4 continuous hours of headache meeting the ICHD-II criteria for migraine or probable migraine.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Frequency of Migraine/Probable Migraine Headache Days | Baseline | 19.2 Migraine/Probable Migraine Headache Days | Standard Deviation 3.94 |
| Botulinum Toxin Type A | Change in Frequency of Migraine/Probable Migraine Headache Days | Change from Baseline at Week 24 | -8.7 Migraine/Probable Migraine Headache Days | Standard Deviation 6.64 |
| Placebo (Saline) | Change in Frequency of Migraine/Probable Migraine Headache Days | Baseline | 18.7 Migraine/Probable Migraine Headache Days | Standard Deviation 4.05 |
| Placebo (Saline) | Change in Frequency of Migraine/Probable Migraine Headache Days | Change from Baseline at Week 24 | -6.3 Migraine/Probable Migraine Headache Days | Standard Deviation 6.71 |
Secondary
Change in Frequency of Moderate/Severe Headache Days
Mean change from baseline in frequency (number) of moderate/severe headache days during the 28 day period ending with Week 24. Those calendar days with \>= 4 continuous hours of headache were selected. As per the patient diary, all headache episodes occurring during those days with a maximum severity of moderate or severe were counted.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Frequency of Moderate/Severe Headache Days | Baseline | 18.1 Moderate/Severe Headache Days | Standard Deviation 4.03 |
| Botulinum Toxin Type A | Change in Frequency of Moderate/Severe Headache Days | Change from Baseline at Week 24 | -8.3 Moderate/Severe Headache Days | Standard Deviation 6.37 |
| Placebo (Saline) | Change in Frequency of Moderate/Severe Headache Days | Baseline | 17.7 Moderate/Severe Headache Days | Standard Deviation 4.26 |
| Placebo (Saline) | Change in Frequency of Moderate/Severe Headache Days | Change from Baseline at Week 24 | -5.8 Moderate/Severe Headache Days | Standard Deviation 6.59 |
Secondary
Change in Total Cumulative Hours of Headache Occurring on Headache Days
Mean change from baseline in total cumulative hours of headache occurring on headache days during the 28 day period ending with Week 24. Headache day defined as a calendar day \[00:00 to 23:59\] when the patient reported \>= 4 continuous hours of headache.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Total Cumulative Hours of Headache Occurring on Headache Days | Baseline | 296.18 Hours | Standard Deviation 121.043 |
| Botulinum Toxin Type A | Change in Total Cumulative Hours of Headache Occurring on Headache Days | Change from Baseline at Week 24 | -132.41 Hours | Standard Deviation 130.216 |
| Placebo (Saline) | Change in Total Cumulative Hours of Headache Occurring on Headache Days | Baseline | 287.20 Hours | Standard Deviation 118.089 |
| Placebo (Saline) | Change in Total Cumulative Hours of Headache Occurring on Headache Days | Change from Baseline at Week 24 | -90.01 Hours | Standard Deviation 133.758 |
Secondary
Percentage of Patients With Severe HIT-6 Impact Category Scores
Percentage of patients with a severe (60-78) score on the Headache Impact Test (HIT-6) Questionnaire during the 28 day period, ending with Week 24. The HIT-6 consisted of 6 questions about headache and impact on the patient's health and well-being. Answers for each question ranged from 6=Never, 8=Rarely, 10=Sometimes, 11=Very Often, and 13=Always. The total scores ranged from 36-49 (Little or No Impact), 50-55 (Some Impact), 56-59 (Substantial Impact) and 60-78 (Severe Impact).
Time frame: Week 24
Population: Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Botulinum Toxin Type A | Percentage of Patients With Severe HIT-6 Impact Category Scores | 66.3 Percentage of Patients |
| Placebo (Saline) | Percentage of Patients With Severe HIT-6 Impact Category Scores | 76.5 Percentage of Patients |