Study of BOTOX Injections in Prevention of Migraine in Adult Participants With Episodic Migraine

Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study of BOTOX (Botulinum Toxin Type A) for the Prevention of Migraine in Subjects With Episodic Migraine

Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound (International Classification of Headache Disorders, 2018). Migraine can be further categorized according to the frequency of attacks as episodic migraine (EM) or chronic migraine (CM). This study will assess the effects of BOTOX in preventing migraine in adult participants with EM.

BOTOX is being developed for the prevention of migraine in adults with episodic migraine (EM). Participants will be enrolled in 3 different treatment groups. There is 1 in 3 chance that participants will be assigned to receive placebo. Approximately 777 adult participants with EM will be enrolled in approximately 125 sites across the world.

Participants will receive intramuscular injections (injected into the muscle) of BOTOX or Placebo on Day 1 and Week 12. Eligible participants will receive BOTOX on Week 24 and Week 36.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Terminated
• Conditions: Episodic Migraine
• Intervention / Treatment: Drug: Placebo; Drug: BOTOX

• Study Type: Interventional
• Enrollment (Actual): 775
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • CHAMP Clinic /ID# 231635
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Vancouver Island Health Authority /ID# 231992
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3R 1V9
      • Maritime Neurology /ID# 232048
  • Ontario
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program /ID# 240006
  • Quebec
    • Lévis, Quebec, Canada, G6W 0M5
      • Clinique Neuro Levis /ID# 232049
• Czechia
  • Jihlava, Czechia, 586 01
    • Nemocnice Jihlava, prispevkova organizace /ID# 232164
  • Prague, Czechia, 100 00
    • Clintrial s.r.o. /ID# 232208
  • Prague, Czechia, 120 00
    • DADO MEDICAL s.r.o. /ID# 232157
  • Prague, Czechia, 140 00
    • Axon Clinical, s.r.o. /ID# 232212
  • Prague, Czechia, 140 59
    • Fakultni Thomayerova nemocnice /ID# 232214
  • Brno-mesto
    • Brno, Brno-mesto, Czechia, 656 91
      • Fakultní Nemocnice U Sv. Anny V Brně /ID# 232213
  • Ostrava-mesto
    • Ostrava, Ostrava-mesto, Czechia, 708 52
      • Fakultni Nemocnice Ostrava /ID# 232211
• Germany
  • Berlin, Germany, 10117
    • Zentrum für Neurologie, Neurochirurgie und Psychiatrie /ID# 232472
  • Essen, Germany, 45133
    • Praxis Dr. Gendolla /ID# 232474
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen /ID# 232478
  • Halle, Germany, 06120
    • Universitaetsklinikum Halle (Saale) /ID# 241506
  • Kassel, Germany, 34131
    • Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 232475
  • Bavaria
    • Munich, Bavaria, Germany, 81344
      • Duplicate_Neurologie Klinikum Großhadern /ID# 232479
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 65929
      • Duplicate_Kopfschmerzzentrum Frankfurt /ID# 234066
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Universitaetsmedizin Rostock /ID# 232471
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden /ID# 239283
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24149
      • Schmerzklinik Kiel /ID# 232480
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 238732
  • Central District
    • Kfar Saba, Central District, Israel, 4420123
      • Maccabi Healthcare Services /ID# 238605
  • Haifa District
    • Hadera, Haifa District, Israel, 38100
      • Hillel Yaffe Medical Center /ID# 232122
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Shaare Zedek Medical Center /ID# 239485
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 232119
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 232598
• Poland
  • Wroclaw, Poland, 52-210
    • MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak /ID# 241887
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-529
      • Solumed Centrum Medyczne /ID# 238446
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-539
      • Specjalistyczne Gabinety Sp. z o.o. /ID# 233526
    • Krakow, Lesser Poland Voivodeship, Poland, 30-721
      • Linden Sp. z o.o. sp.k. /ID# 245685
    • Oświęcim, Lesser Poland Voivodeship, Poland, 32-600
      • Instytut Zdrowia Dr Boczarska Jedynak /ID# 251857
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-582
      • Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 232355
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-119
      • Warszawska Klinika Sp. z o.o. /ID# 240612
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-282
      • Silmedic Sp. z o.o. /ID# 232358
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 232268
  • Madrid, Spain, 28027
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 233320
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz /ID# 232495
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid /ID# 232272
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Pamplona /ID# 232270
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias /ID# 232428
• Sweden
  • Upplands Vasby, Sweden, 194 61
    • Optimuskliniken /ID# 232174
  • Skåne County
    • Lund, Skåne County, Sweden, 227 33
      • Skaneuro Privatmottagning /ID# 232175
  • Stockholm County
    • Stockholm, Stockholm County, Sweden, 114 33
      • Neurology Clinic /ID# 234067
  • Östergötland County
    • Linköping, Östergötland County, Sweden, 581 85
      • Linkoping University Hospital /ID# 234040
• United Kingdom
  • Inverness, United Kingdom, IV2 3UJ
    • NHS Highland /ID# 242855
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre /ID# 242857
  • London, United Kingdom, EC2Y 8EA
    • St Pancras Clinical Research /ID# 242764
  • East Riding Of Yorkshire
    • Hull, East Riding Of Yorkshire, United Kingdom, HU3 2JZ
      • Hull University Teaching Hospitals NHS Trust /ID# 242763
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G51 4TF
      • Duplicate_Queen Elizabeth University Hospital /ID# 244870
• United States
  • Alabama
    • Hoover, Alabama, United States, 35244-5700
      • Neurology and Neurodiagnostics of Alabama /ID# 231918
    • Huntsville, Alabama, United States, 35805-4046
      • Rehabilitation & Neurological Services /ID# 252441
  • Arizona
    • Phoenix, Arizona, United States, 85012-2707
      • Alea Research /ID# 233329
    • Phoenix, Arizona, United States, 85013-4407
      • Duplicate_Barrow Neurological Institute /ID# 231799
    • Scottsdale, Arizona, United States, 85258-4595
      • Clinical Endpoints /ID# 232625
    • Tucson, Arizona, United States, 85710-6152
      • Tucson Neuroscience Research /ID# 232288
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Clinical Research /ID# 231640
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group /ID# 231492
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research /ID# 232189
    • Encino, California, United States, 91316
      • Pharmacology Research Institute (PRI) - Encino (Wake) /ID# 231351
    • Fresno, California, United States, 93710-5473
      • Duplicate_Neuro Pain Medical Center /ID# 231478
    • Imperial, California, United States, 92251-9401
      • Sun Valley Research Center /ID# 231350
    • Los Alamitos, California, United States, 90720
      • Wake Research - Pharmacology Research Institute (WR-PRI), LLC (Alamitos) /ID# 231908
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute (PRI) - Newport Beach (Wake) /ID# 231337
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates (CSNA) /ID# 230662
    • Englewood, Colorado, United States, 80113-3781
      • Summit Headache and Neurologic Institute /ID# 231809
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research, LLC /ID# 230658
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Hospital /ID# 232129
  • Florida
    • Boca Raton, Florida, United States, 33428-2231
      • Neurology Offices of South Florida, PLLC /ID# 232281
    • Bradenton, Florida, United States, 34209-4616
      • Nova Clinical Research, LLC /ID# 245256
    • Hallandale, Florida, United States, 33009-4427
      • Velocity Clinical Research - Hallandale Beach /ID# 232442
    • Jacksonville, Florida, United States, 32256-6039
      • CNS Healthcare - Jacksonville /ID# 231345
    • Miami, Florida, United States, 33176-2315
      • Brainstorm Research /ID# 243825
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare /ID# 231340
    • Orlando, Florida, United States, 32801-2986
      • Clinical Neuroscience Solutions, Inc /ID# 231362
    • Sun City Center, Florida, United States, 33573-6828
      • Pain Relief Centers /ID# 232415
    • Tampa, Florida, United States, 33615
      • Olympian Clinical Research - Tampa /ID# 239519
    • Tampa, Florida, United States, 33634
      • Accel Research Sites - Tampa Clinical Research Unit /ID# 231670
    • Tampa, Florida, United States, 33613
      • University of South Florida- Neuroscience Institute /ID# 231808
    • West Palm Beach, Florida, United States, 33407-3209
      • Premiere Research Institute - Palm Beach /ID# 230646
    • Winter Park, Florida, United States, 32789
      • Conquest Research /ID# 232604
  • Georgia
    • Decatur, Georgia, United States, 30030-2627
      • Accel Research Sites Neurostudies /ID# 230665
    • Decatur, Georgia, United States, 30030
      • CenExcel iResearch LLC /ID# 231335
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute /ID# 239517
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials /ID# 230657
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research - Boise /ID# 230660
  • Illinois
    • Riverwoods, Illinois, United States, 60015-5711
      • Robbins Headache Clinic /ID# 230970
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson-Wallack-Munshower Neurology - Northeast /ID# 230654
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic - Gateway Health Center /ID# 231329
  • Iowa
    • Ames, Iowa, United States, 50010
      • Duplicate_Accellacare - McFarland Clinic /ID# 231496
  • Kansas
    • Overland Park, Kansas, United States, 66211-1363
      • Kansas Institute of Research /ID# 231862
  • Louisiana
    • Covington, Louisiana, United States, 70433-8107
      • Ochsner Clinic Foundation /ID# 230645
  • Massachusetts
    • Boston, Massachusetts, United States, 02130-3446
      • Brigham and Women's Faulkner Hospital /ID# 231865
    • Boston, Massachusetts, United States, 02131-2515
      • Boston Clinical Trials /ID# 231367
  • Michigan
    • Ann Arbor, Michigan, United States, 48104-5131
      • Michigan Headache & Neurological Institute (MHNI) /ID# 230659
  • Minnesota
    • Burnsville, Minnesota, United States, 55337-6732
      • Minneapolis Clinic of Neurology - Burnsville /ID# 231780
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research /ID# 230642
    • Springfield, Missouri, United States, 65807
      • Clinvest Research LLC /ID# 252440
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research /ID# 232188
    • North Las Vegas, Nevada, United States, 89030-7187
      • Las Vegas Clinical Trials /ID# 232628
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc. /ID# 231101
  • New York
    • Amherst, New York, United States, 14226
      • Duplicate_Dent Neurosciences Research Center, Inc. /ID# 252442
    • New York, New York, United States, 10017-1921
      • Fieve Clinical Research, Inc. /ID# 231365
    • The Bronx, New York, United States, 10461-2720
      • Montefiore Headache Center /ID# 232130
    • Williamsville, New York, United States, 14221-6046
      • Upstate Clinical Research Associates /ID# 231343
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center /ID# 230819
    • Raleigh, North Carolina, United States, 27612-8106
      • M3 Wake Research Inc. /ID# 232285
    • Winston-Salem, North Carolina, United States, 27103-6984
      • Neurology - Triad /ID# 231733
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0585
      • Duplicate_Duplicate_University Of Cincinnati Medical Center /ID# 231739
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company /ID# 231085
    • Oklahoma City, Oklahoma, United States, 73116-1423
      • Cutting Edge Research Group /ID# 231095
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Institute of Oklahoma City /ID# 231349
    • Oklahoma City, Oklahoma, United States, 73116
      • Sooner Clinical Research /ID# 231096
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates - Abington /ID# 231798
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Center for Clinical Research /ID# 231355
    • Media, Pennsylvania, United States, 19063-1760
      • Suburban Research Associates - Media /ID# 231354
    • Philadelphia, Pennsylvania, United States, 19107-5191
      • Jefferson Hospital for Neuroscience /ID# 230664
    • Smithfield, Pennsylvania, United States, 15478
      • Duplicate_Frontier Clinical Research /ID# 232623
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of SC /ID# 231369
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - North Charleston /ID# 231353
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions - Memphis /ID# 231328
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group /ID# 231642
  • Texas
    • Austin, Texas, United States, 78737
      • Austin Clinical Trial Partners /ID# 231092
    • Dallas, Texas, United States, 75214
      • Texas Neurology /ID# 230661
    • Houston, Texas, United States, 77094-1385
      • NeuroCare Plus /ID# 252499
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research /ID# 231368
    • Falls Church, Virginia, United States, 22043-2367
      • Integrated Neurology Services - Falls Church /ID# 244776
    • Virginia Beach, Virginia, United States, 23451
      • Tidewater Integr Med Research /ID# 231359
    • Virginia Beach, Virginia, United States, 23456-0019
      • Sentara Neurology Specialists - Virginia Beach /ID# 231341
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center /ID# 231336
    • Tacoma, Washington, United States, 25328
      • Puget Sound Neurology /ID# 230640
  • West Virginia
    • Kingwood, West Virginia, United States, 26537-9797
      • Frontier Clinical Research - Kingwood /ID# 234127

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of migraine headache disorder meeting International Classification of Headache Disorders (ICHD)-3 diagnostic criteria for migraine with aura or migraine without aura for >= 12 months.
• Onset of migraine before 50 years of age.
• History of 6 to 14 migraine days/month in each of the 3 months prior to Visit 1.
• Six to 14 migraine/probable migraine days during the 4-week screening/baseline phase.
• Less than 15 headache days/month in each of the 3 months prior to Visit 1 and during the 4-week screening/baseline phase.

Exclusion Criteria:

• Current diagnosis of chronic migraine according to ICHD-3.
• History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, chronic tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache.
• History of headache attributed to another disorder (e.g., cervical dystonia, craniotomy, head/neck trauma) with exception that medication overuse headache per ICHD-3 criteria is allowed.
• History of inadequate response to > 4 prophylactic treatment for migraine, 2 of which have different mechanisms of action.
• Female who is pregnant, breastfeeding, or considering becoming pregnant during the study or within 90 days after the last dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Double-Blind Phase: Placebo; Participants received placebo for BOTOX intramuscular injections in the head/neck muscles on Day 1 and Week 12.	Drug: Placebo; Intramuscular Injection
Experimental: Double-Blind Phase: BOTOX 155 U; Participants received intramuscular injections of BOTOX 155 U in the head/neck muscles on Day 1 and Week 12.	Drug: BOTOX; Intramuscular Injection; Other Names: Botulinum Toxin Type A
Experimental: Double-Blind Phase: BOTOX 195 U; Participants received intramuscular injections of BOTOX 195 U in the head/neck muscles on Day 1 and Week 12.	Drug: BOTOX; Intramuscular Injection; Other Names: Botulinum Toxin Type A
Experimental: Open-Label Phase: BOTOX 195 U; Eligible participants received intramuscular injections of BOTOX 195 U in the head/neck muscles on Weeks 24 and 36.	Drug: BOTOX; Intramuscular Injection; Other Names: Botulinum Toxin Type A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6	The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.	Baseline, Months 5-6
Number of Participants With Treatment-Emergent Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.	Double-Blind Phase (Week 0-24); Open-Label Phase (Week 24-48)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Frequency of Monthly Headache Days Across Months 5 and 6	The frequency of monthly headache days across Months 5 and 6 is calculated by taking the 2-month average of monthly headache days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.	Baseline, Months 5-6
Percentage of Participants With ≥ 50% Reduction From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6	The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. The responder status of 50% reduction from Baseline is defined as a participant with at least a 50% reduction from Baseline in the 2-month average of monthly migraine days over Months 5 and 6.	Baseline, Months 5-6
Change From Baseline in the Frequency of Monthly Acute Headache Medication Days Across Months 5 and 6	Monthly acute headache medication days across Months 5 and 6 is calculated by taking the 2-month average of monthly acute headache medication days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.	Baseline, Months 5-6
Change From Baseline in Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) Role Function - Restrictive (RFR) Domain Score At Month 6	The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine over the past 4 weeks. It is divided into 3 domains, and the Role Function Restrictive (RFR) assesses how migraines limit one's daily social and work-related activities using a 6-point scale ranging from "none of the time" to "all of the time". Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life. Positive changes from Baseline indicate improvement.	Baseline, Month 6
Change From Baseline in the Activity Impairment in Migraine - Diary (AIM-D) Physical Impairment Domain Score Across Months 5 and 6	AIM-D Physical Impairment Domain score is calculated based on the summation of AIM-D items 6-9. Participants answer each question based on the level of difficulty experienced in the 24 hours prior, with "during your headache" indicated for when they reported a headache, using a 6-point rating scale ranging from "not difficult at all" to "extremely difficult". The raw daily score is transformed to a 0-100 scale, and the monthly score is calculated using the average daily scores, where a higher score indicates worse physical impairment. AIM-D Physical Impairment domain score across Months 5 and 6 is calculated by taking the 2-month average of AIM-D Physical Impairment domain scores over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.	Baseline, Months 5-6
Change From Baseline in the Total 6-item Headache Impact Test (HIT-6) Score Across Months 5 and 6	The HIT-6 is a 6-item assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home and in social situations. It assesses the effect that headaches have on normal daily life and the subject's ability to function. Responses are based on frequency using a 5-point scale ranging from "never" to "always." The HIT-6 total score, which ranges from 36 to 78, is the sum of the responses, each of which is assigned a score ranging from 6 points (never) to 13 points (always). The Total 6-item Headache Impact Test (HIT-6) score across Months 5 and 6 is calculated by taking the 2-month average of total 6-item Headache Impact Test (HIT-6) scores over Months 5 and 6. Negative changes from Baseline in the HIT-6 score indicate improvement.	Baseline, Months 5-6

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2021
• Primary Completion (Actual): November 6, 2024
• Study Completion (Actual): November 6, 2024

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Migraine; Botulinum Toxin Type A; Episodic Migraine; BOTOX
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Metalloproteases; Bacterial Proteins; Bacterial Toxins; Toxins, Biological; Botulinum Toxins, Type A
• Other Study ID Numbers: M21-307; 2021-001979-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No