12-Week Placebo-controlled Study of Atogepant for the Preventive Treatment of Migraine in Participants With Episodic Migraine

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Atogepant for the Prevention of Migraine in Participants With Episodic Migraine (ADVANCE)

To evaluate the safety and tolerability of atogepant 30 mg and 60 mg once a day for the prevention of migraine in participants with episodic migraine.

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Atogepant

• Study Type: Interventional
• Enrollment (Actual): 910
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus Clinical Research US, Inc.
    • Glendale, Arizona, United States, 85308
      • Advanced Research Associates
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85012
      • Alea Research Institute
    • Tucson, Arizona, United States, 85741
      • Orange Grove Family Practice
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Principals Research Group
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Clinical Research
  • California
    • Carmichael, California, United States, 95608
      • Med Center Medical Clinic
    • El Cajon, California, United States, 92020
      • TriWest Research Associates
    • Fresno, California, United States, 93710
      • Neuro Pain Medical Center
    • Fresno, California, United States, 93720
      • California Headache and Balance Center
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • Irvine, California, United States, 92618
      • NervePro Research Bruce Cleeremans
    • La Mesa, California, United States, 91942
      • Grossmont Center for Clinical Research
    • Lomita, California, United States, 90731
      • Torrance Clinical Research Institute, Inc.
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials Services
    • Los Angeles, California, United States, 90033
      • Keck Medicine of USC
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Newport Beach, California, United States, 92663
      • Newport Beach Clinical Research Associates
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Palo Alto, California, United States, 94304
      • Stanford
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga Clinical Research
    • Redlands, California, United States, 92374
      • Desert Valley Research
    • Redondo Beach, California, United States, 90277
      • George J. Rederich, M.D. Inc.
    • San Diego, California, United States, 92117
      • Paradigm Clinical Research Centers, Inc
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research
    • Vista, California, United States, 92083
      • Synexus Clinical Research US, Inc.
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, Inc.
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates
    • Englewood, Colorado, United States, 80113
      • Colorado Neurological Institute
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura Neurological Associates
    • Boca Raton, Florida, United States, 33428
      • Neurology Offices of South Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials- Gainesville
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Maitland, Florida, United States, 32751
      • Neurology Associates, P.A.
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research, Corp.
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital Clinical Research Center
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus Clinical Research US, Inc.
    • Atlanta, Georgia, United States, 30328
      • Neurotrials Research
    • Atlanta, Georgia, United States, 30328
      • Pediatric and Adolescent NeuroDevelopmental Associates (PANDA) Neurology
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60642
      • Diamond Headache Clinic Ltd
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • JWM Neurology
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic - Gateway Health Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • PMG Research, Inc. d/b/a PMG Research of McFarland Clinic
  • Kansas
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center
    • Prairie Village, Kansas, United States, 66208
      • Phoenix Medical Research
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC - An AMR Company
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC - An AMR Company
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70124
      • Delricht Research
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
    • Largo, Maryland, United States, 20774
      • Mid-Atlantic Permanente Medical Group, PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • John R. Graham Headache Center Brigham and Women's Faulkner Hospital
    • New Bedford, Massachusetts, United States, 02740
      • BTC of New Bedford
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • Mississippi
    • Bay Saint Louis, Mississippi, United States, 63141
      • Synexus USA
    • Ridgeland, Mississippi, United States, 39157
      • The Headache Center
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65810
      • Clinvest Research LLC.
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Synexus Clinical Research US, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Nevada Headache Institute
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Great Neck, New York, United States, 11021
      • Northwell Health
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • PMG Research of Charlotte, LLC
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Associates, Inc
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh, LLC
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates, P.A.
    • Rocky Mount, North Carolina, United States, 27804
      • PMG Research of Rocky Mount, LLC
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research of Winston-Salem
  • Ohio
    • Akron, Ohio, United States, 44311
      • Synexus Clinical Research US, Inc.
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites
    • Cincinnati, Ohio, United States, 45242
      • Sentral Clinical Research Services
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
    • Lyndhurst, Ohio, United States, 44124
      • Family Physicians Associates
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research, LLC
    • Norman, Oklahoma, United States, 73069
      • Lynn Institute of Norman
    • Oklahoma City, Oklahoma, United States, 73111
      • Centennial Health-Synexus
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research
  • Oregon
    • Portland, Oregon, United States, 97214
      • Oregon Center for Clinical Investigations
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research, LLC
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians, Jacob Murphy
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Partners in Clinical Research
    • Lincoln, Rhode Island, United States, 02865
      • Ocean State Clinical Research Partners
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Primary Care Associates/Synexus Clinical
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research US, Inc
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • Simpsonville, South Carolina, United States, 29681
      • Hillcrest Family Practice
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare - Memphis
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Austin, Texas, United States, 78737
      • Psychiatry & Psychotherapy Partners Austin
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75234
      • Synexus-US
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • San Antonio, Texas, United States, 78229
      • Synexus Clinical Research US, Inc.
    • Waxahachie, Texas, United States, 75165
      • ClinPoint Trials
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus-US
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc.
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Family Medicine Physicians
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Clinical Research Center
    • Everett, Washington, United States, 98201
      • Eastside Therapeutic Resource and Core Clinical Research
    • Seattle, Washington, United States, 98104
      • The Polyclinic
    • Tacoma, Washington, United States, 25328
      • Puget Sound Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least a 1-year history of migraine with or without aura consistent with a diagnosis.
• Age of the participant at the time of migraine onset <50 years.

Exclusion Criteria:

• Has a history of migraine accompanied by diplopia or decreased level of consciousness or retinal migraine.
• Has a current diagnosis of chronic migraine, new persistent daily headache, trigeminal autonomic cephalgia (e.g., cluster headache), or painful cranial neuropathy.
• History of an inadequate response to >4 medications (2 of which have different mechanisms of action) prescribed for the prevention of migraine.
• Participants with clinically significant hematologic, endocrine, cardiovascular, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo-matching atogepant tablets orally once daily for 12 weeks.	Drug: Placebo; Placebo-matching atogepant tablets
Experimental: Atogepant 10 mg; Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Drug: Placebo; Placebo-matching atogepant tablets; Drug: Atogepant; Atogepant tablet
Experimental: Atogepant 30 mg; Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Drug: Placebo; Placebo-matching atogepant tablets; Drug: Atogepant; Atogepant tablet
Experimental: Atogepant 60 mg; Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Drug: Placebo; Placebo-matching atogepant tablets; Drug: Atogepant; Atogepant tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Migraine Days Across the 12-Week Treatment Period	Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days was defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. A Mixed-effects model for repeated measures (MMRM) was used for analysis.	Baseline (Day -28 to Day -1) to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period	Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache qualified by duration or acute symptomatic medication use. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of migraine days during the last 28 days of the Baseline phase, from Day -28 to -1. Negative change from Baseline indicates improvement. MMRM was used for analysis.	Baseline (Day-28 to Day -1) to Week 12
Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period	Participants recorded allowed medication(s) to treat an acute migraine in the daily diary. The monthly (4-week) acute medication use days was defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline was defined as the number of acute medication use days during the last 28 days of the Baseline phase, from Day -28 to -1. A negative change from Baseline indicates improvement. MMRM was used for the analysis.	Baseline (Day-28 to Day -1) to Week 12
Percentage of Participants With at Least a 50% Reduction (Improvement) in 3-month Average of Monthly Migraine Days	Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache qualified by duration or acute symptomatic medication use. The monthly (4-week) migraine days is equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28. Each 4-week period was averaged.	Baseline (Day -28 to Day -1) to Week 12
Change From Baseline in Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score at Week 12	MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality-of-life impairments attributed to migraine in the past 4 weeks. It is divided into three domains: role function-restrictive (questions 1-7, score range 7 to 42) assesses how migraines limit one's daily social and work-related activities; role function-preventive (questions 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the emotional function (questions 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale where 1=none of the time and 6=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 from Baseline indicate better quality of life. MMRM was used for the analysis.	Baseline (Day 1) to Week 12
Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the Activity Impairment in Migraine-Diary (AIM-D) Across the 12-Week Treatment Period	The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw performance of daily activities domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). Baseline was defined as the monthly (averaged for a month) performance of daily activities domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis.	Baseline (Day -28 to Day -1) to Week 12
Change From Baseline in Mean Monthly Physical Impairment Domain Score of the Activity Impairment in Migraine- Diary (AIM-D) Across the 12-Week Treatment Period	The AIM-D is a 9-item PRO measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw physical impairment domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden). Baseline was defined as the monthly (averaged for a month) physical impairment domain score during the last 28 days of the Baseline period from Day -28 to -1. MMRM was used for the analysis.	Baseline (Day -28 to Day -1) to Week 12

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

General Publications

• Boinpally R, McNamee B, Yao L, Butler M, McGeeney D, Borbridge L, Periclou A. A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single-Dose, Phase 1 Crossover Trial. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1099-1107. doi: 10.1002/cpdd.940. Epub 2021 May 4.
• Min KC, Kraft WK, Bondiskey P, Colon-Gonzalez F, Liu W, Xu J, Panebianco D, Mixson L, Dockendorf MF, Matthews CZ, Boinpally R. Atogepant Is Not Associated With Clinically Meaningful Alanine Aminotransferase Elevations in Healthy Adults. Clin Transl Sci. 2021 Mar;14(2):599-605. doi: 10.1111/cts.12917. Epub 2020 Nov 24.
• Lipton RB, Pozo-Rosich P, Blumenfeld A, Li Y, Severt L, Stokes JT, Creutz L, Gandhi P, Dodick D. Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial. Neurology. 2022 Nov 17:10.1212/WNL.0000000000201568. doi: 10.1212/WNL.0000000000201568. Online ahead of print.
• Lipton RB, Pozo-Rosich P, Blumenfeld AM, Dodick DW, McAllister P, Li Y, Lu K, Dabruzzo B, Miceli R, Severt L, Finnegan M, Trugman JM. Rates of Response to Atogepant for Migraine Prophylaxis Among Adults: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Jun 1;5(6):e2215499. doi: 10.1001/jamanetworkopen.2022.15499.
• Schwedt TJ, Lipton RB, Ailani J, Silberstein SD, Tassorelli C, Guo H, Lu K, Dabruzzo B, Miceli R, Severt L, Finnegan M, Trugman JM. Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial. Cephalalgia. 2022 Jan;42(1):3-11. doi: 10.1177/03331024211042385. Epub 2021 Sep 14.
• Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706. doi: 10.1056/NEJMoa2035908.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Actual): June 19, 2020
• Study Completion (Actual): June 19, 2020

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Migraine; Aura
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 3101-301-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No