Study of Oral Atogepant When Added to OnabotulinumtoxinA (BOTOX) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Chronic Migraine (ATO-BOTOX)

A Phase 3 Multicenter 24-Week Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Atogepant When Added to OnabotulinumtoxinA (BOTOX) for the Preventive Treatment of Chronic Migraine

Migraine is characterized by attacks of throbbing, moderate or severe headache, often associated with nausea, vomiting, and/or sensitivity to light and/or sound. The study will assess safety and tolerability of atogepant when added to BOTOX, as well as prospectively evaluate the efficacy of add-on atogepant for migraine prevention. Adverse events and change in disease activity will be monitored.

Atogepant is an investigational drug being developed to prevent chronic migraine. Approximately 75 adult participants will be enrolled at approximately 30 sites in the United States.

All participants will receive atogepant oral tablet once a day (QD) during the 24-week treatment period, in addition to their standard of care Botox.

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: Completed
• Conditions: Chronic Migraine
• Intervention / Treatment: Drug: Atogepant

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Hoover, Alabama, United States, 35244-5700
      • Neurology and Neurodiagnostics of Alabama /ID# 242538
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute - Dignity Health St. Joseph's Hosp and Medical Ctr /ID# 241812
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Clinical Research /ID# 241789
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research /ID# 241772
    • Carlsbad, California, United States, 92011-4213
      • Profound Research LLC /ID# 244084
    • Fresno, California, United States, 93710
      • Neuro Pain Medical Center /ID# 241992
    • Santa Monica, California, United States, 90404
      • Neurological Research Institute /ID# 242688
  • Florida
    • Boca Raton, Florida, United States, 33428-2231
      • Neurology Offices of South Florida, PLLC /ID# 242693
    • Jacksonville Beach, Florida, United States, 32250-1694
      • Coastal Clinical Research Specialists /ID# 247992
    • Miami, Florida, United States, 33136
      • University of Miami /ID# 252230
    • Sarasota, Florida, United States, 34239-2943
      • First Physicians Group - Waldemere /ID# 242861
  • Kansas
    • Overland Park, Kansas, United States, 66211-1363
      • Kansas Institute of Research /ID# 241796
  • Louisiana
    • Covington, Louisiana, United States, 70433-8107
      • Duplicate_Ochsner Clinic Foundation /ID# 241803
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 241800
  • Michigan
    • Ann Arbor, Michigan, United States, 48104-5131
      • Michigan Headache & Neurological Institute (MHNI) /ID# 241784
  • Minnesota
    • Burnsville, Minnesota, United States, 55337-6732
      • Minneapolis Clinic of Neurology - Burnsville /ID# 241994
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College /ID# 242757
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute - Amherst /ID# 241776
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center /ID# 241791
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5191
      • Jefferson Hospital for Neuroscience /ID# 243712
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians - Jacob Murphy /ID# 241798
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-3239
      • Chattanooga Medical Research /ID# 253295
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group /ID# 243592
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology /ID# 241795
  • Virginia
    • Falls Church, Virginia, United States, 22043-2367
      • Integrated Neurology Services - Falls Church /ID# 244747
    • Falls Church, Virginia, United States, 22042
      • Inova Health System /ID# 252242
  • Washington
    • Tacoma, Washington, United States, 25328
      • Puget Sound Neurology /ID# 241787
  • West Virginia
    • Kingwood, West Virginia, United States, 26537-9797
      • Frontier Clinical Research - Kingwood /ID# 242928
    • Morgantown, West Virginia, United States, 26506
      • West Virginia Univ School Med /ID# 252869

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least a 1-year history of chronic migraine (CM), with or without aura, consistent with a diagnosis according to International Classification of Headache Disorders 3rd edition (ICHD-3 2018) and with or without acute medication overuse as defined in the protocol.
• Must be currently treated with BOTOX for CM: treated with >= 2 treatment cycles in the 8 months prior to Visit 2 (Day 1) with documentation of payer authorization or written attestation of self-pay to support continued use of BOTOX.
• Must have 8 to 23 (inclusive) migraine days in the electronic diary [eDiary] screening/baseline period (eDiary data must have been collected for at least 20 days).

Exclusion Criteria:

• Use of opioid-containing products for more than 4 days per month for acute treatment of headache in the 3 months prior to Screening or during the screening/baseline period.
• Treatment of study target muscles using acupuncture, transcutaneous electrical nerve stimulation (TENS), cranial traction, dental splints for headache, or head and/or neck injections of anesthetics/steroids within 4 weeks prior to Screening and throughout the study.
• Concurrent use of any migraine prevention treatment other than BOTOX (required concomitant medication; or topiramate <=100mg daily) including use of oral gepants in the 4 weeks prior to screening nor during the screening/baseline period.
• Current use or use within the 6 months (24 weeks) prior to Screening, of mAbs blocking the CGRP pathway.
• Concurrent use of oral gepants for acute migraine treatment in the 4 weeks prior to screening nor during the screening/baseline period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atogepant; Participants received atogepant 60 mg once a day (QD) during the 24-week treatment period.	Drug: Atogepant; Oral Tablet; Other Names: QULIPTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 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.	From first dose of study drug until 4 weeks following last dose of study drug (up to 28 weeks)
Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values (Chemistry, Hematology, Urinalysis) as Assessed by the Investigator	Clinical laboratory test values are considered PCS if they meet either the lower-limit or higher-limit PCS criteria defined in the categories below. The percentage of participants with PCS laboratory values are summarized for hematology, chemistry, and urinalysis. Glomerular Filtration Rate (GFR) is a clinical measurement that calculates how many milliliters of blood the kidneys filter every second. Glucose, Urinalysis: At least 1+ indicates that the urine contains an increased concentration of sugar. Protein, Urinalysis: At least 1+ indicates that the urine contains an increased concentration of protein.	From first dose of study drug until last dose of study drug (24 weeks)
Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator	Potentially Clinically Significant post-Baseline vital sign values are summarized for categories: systolic and diastolic blood pressures [sitting], pulse rate [sitting], and weight. Number of participants with non-PCS baseline values who met the PCS criterion at least once post-baseline are reported.	From first dose of study drug until last dose of study drug (24 weeks)
Percentage of Participants With Most Severe Suicidal Ideation and Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Open-Label Treatment Period	The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. (Minimum total score 0, maximum total score 5; higher total scores indicate more suicidal ideation and/or suicidal behavior).	From first dose of study drug until last dose of study drug (24 weeks)
Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator	12-lead ECGs were performed at select study visits.	From first dose of study drug until last dose of study drug (24 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Migraine Days	Change from Baseline in monthly migraine days, defined by IHS Guidelines 2018 will be assessed.	Baseline (Week 0) through 24 Weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Rothrock J, Najib U, Ailani J, Ashina S, Bao J, Smith JH, Adams AM, Dabruzzo B, Pfleeger K, Blumenfeld A. Safety, tolerability, and efficacy of atogepant added to onabotulinumtoxinA for the preventive treatment of chronic migraine: A phase 3, multicenter, 24-week, open-label study. Cephalalgia. 2026 Apr;46(4):3331024261429118. doi: 10.1177/03331024261429118. Epub 2026 Apr 7.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Actual): May 2, 2025
• Study Completion (Actual): May 2, 2025

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Migraine; OnabotulinumtoxinA; Chronic Migraine; BOTOX; Atogepant; QULIPTA
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; atogepant
• Other Study ID Numbers: M22-418

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