Migraine Disorders
Conditions
Brief summary
This is a 60 week study including a double-blind phase followed by an open-label extension phase.
Interventions
BIOLOGICALBotulinum 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.
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
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 Temporomandibular Disorders (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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 ICHD-II criteria for migraine or probable migraine. |
| 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 |
| Change in Frequency of Acute Headache Pain Medication Intakes | Baseline, Week 24 | Mean change from baseline in frequency (number) of acute headache pain medication intakes during the 28 day period ending with Week 24. Medication intakes defined as the number of times a patient took acute headache pain medication regardless of dose or type/number of medications taken at the same time. |
| Change in Frequency of Migraine/Probable Migraine Headache Episodes | Baseline, Week 24 | Mean change from baseline in frequency (number) of migraine/probable migraine 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 and met ICHD-II criteria for migraine or probable migraine. |
Countries
Canada, 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. | 341 |
| 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. | 338 |
| Total | 679 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A | Placebo (Saline) | Total |
|---|---|---|---|
| Age, Customized < 40years | 144 participants | 128 participants | 272 participants |
| Age, Customized >= 40 years | 197 participants | 210 participants | 407 participants |
| Sex: Female, Male Female | 304 Participants | 290 Participants | 594 Participants |
| Sex: Female, Male Male | 37 Participants | 48 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 215 / 624 | 64 / 334 |
| serious Total, serious adverse events | 42 / 624 | 8 / 334 |
Outcome results
Primary
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 | 12.3 Headache Episodes | Standard Deviation 5.23 |
| Botulinum Toxin Type A | Change in Frequency of Headache Episodes | Change from Baseline at Week 24 | -5.2 Headache Episodes | Standard Deviation 5.27 |
| Placebo (Saline) | Change in Frequency of Headache Episodes | Baseline | 13.4 Headache Episodes | Standard Deviation 5.71 |
| Placebo (Saline) | Change in Frequency of Headache Episodes | Change from Baseline at Week 24 | -5.3 Headache Episodes | Standard Deviation 5.85 |
Secondary
Change in Frequency of Acute Headache Pain Medication Intakes
Mean change from baseline in frequency (number) of acute headache pain medication intakes during the 28 day period ending with Week 24. Medication intakes defined as the number of times a patient took acute headache pain medication regardless of dose or type/number of medications taken at the same time.
Time frame: Baseline, Week 24
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change in Frequency of Acute Headache Pain Medication Intakes | Change from Baseline at Week 24 | -10.3 Medication Intakes | Standard Deviation 18.67 |
| Botulinum Toxin Type A | Change in Frequency of Acute Headache Pain Medication Intakes | Baseline | 29.1 Medication Intakes | Standard Deviation 19.27 |
| Placebo (Saline) | Change in Frequency of Acute Headache Pain Medication Intakes | Change from Baseline at Week 24 | -10.4 Medication Intakes | Standard Deviation 18.54 |
| Placebo (Saline) | Change in Frequency of Acute Headache Pain Medication Intakes | Baseline | 30.4 Medication Intakes | Standard Deviation 22.29 |
Secondary
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 | 20.0 Headache Days | Standard Deviation 3.73 |
| Botulinum Toxin Type A | Change in Frequency of Headache Days | Change from Baseline at Week 24 | -7.8 Headache Days | Standard Deviation 6.57 |
| Placebo (Saline) | Change in Frequency of Headache Days | Baseline | 19.8 Headache Days | Standard Deviation 3.71 |
| Placebo (Saline) | Change in Frequency of Headache Days | Change from Baseline at Week 24 | -6.4 Headache Days | Standard Deviation 6.69 |
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 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 | 19.1 Migraine/Probable Migraine Headache Days | Standard Deviation 4.04 |
| Botulinum Toxin Type A | Change in Frequency of Migraine/Probable Migraine Headache Days | Change from Baseline at Week 24 | -7.6 Migraine/Probable Migraine Headache Days | Standard Deviation 6.51 |
| Placebo (Saline) | Change in Frequency of Migraine/Probable Migraine Headache Days | Baseline | 19.1 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 | -6.1 Migraine/Probable Migraine Headache Days | Standard Deviation 6.78 |
Secondary
Change in Frequency of Migraine/Probable Migraine Headache Episodes
Mean change from baseline in frequency (number) of migraine/probable migraine 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 and met 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 Episodes | Baseline | 11.5 Migraine/Prob Migraine Headache Episodes | Standard Deviation 5.06 |
| Botulinum Toxin Type A | Change in Frequency of Migraine/Probable Migraine Headache Episodes | Change from Baseline at Week 24 | -4.8 Migraine/Prob Migraine Headache Episodes | Standard Deviation 5.06 |
| Placebo (Saline) | Change in Frequency of Migraine/Probable Migraine Headache Episodes | Baseline | 12.7 Migraine/Prob Migraine Headache Episodes | Standard Deviation 5.72 |
| Placebo (Saline) | Change in Frequency of Migraine/Probable Migraine Headache Episodes | Change from Baseline at Week 24 | -4.9 Migraine/Prob Migraine Headache Episodes | Standard Deviation 5.74 |