Study of Oral Atogepant Tablets to Assess Change in Disease Activity in Adult Japanese Participants With Episodic Migraine (JPN PIVOTAL)

A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With An Active Treatment Extension to Evaluate the Efficacy, Safety, and Tolerability of Oral Atogepant for the Prevention of Migraine in Japanese Subjects With Episodic Migraine

A migraine is a moderate to severe headache on one side of the head. A migraine attack is a headache that may be accompanied by throbbing, nausea, vomiting, sensitivity to light and sound, or other symptoms. This study will assess how safe and effective three different doses of atogepant is compared to placebo in adult Japanese participants. Change in migraine symptoms will be assessed.

Atogepant (Qulipta) is an approved drug to treat adults with episodic migraine in the United States. Participants are randomly assigned to one of the 4 treatment groups called Arms to receive atogepant or matching placebo. There is 1 in a 4 chance for the participant to receive placebo. This is double-blinded study which means neither study doctor not the participant will know if the participant received atogepant or placebo. Approximately 520 adult participants with episodic migraine will be enrolled in approximately 50 sites across Japan.

Participants will receive oral atogepant or matching placebo tablets once daily for 12 weeks. At 12 weeks participants assigned to atogepant dose A, dose B or dose C will continue to receive same treatment for 12 additional weeks and participants assigned to placebo will be re-randomized to receive atogepant dose A, dose B or dose C for 12 additional weeks. All participants will be followed for 30 days following last dose of study drug.

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 safety and tolerability of the treatment will be checked by medical assessments, blood tests, checking for adverse events and completing questionnaires.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 524
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan, 730-0031
    • DOI Internal Medicine-Neurology Clinic /ID# 245661
  • Kagoshima, Japan, 890-0052
    • Tanaka Neurosurgery & Headache Clinic /ID# 245488
  • Kyoto, Japan, 600-8811
    • Tatsuoka Neurology Clinic /ID# 245328
  • Tokyo, Japan, 108-0075
    • Shinagawa Strings Clinic /ID# 245665
  • Chiba
    • Ichikawa-shi, Chiba, Japan, 272-0824
      • Tokyo Dental College Ichikawa General Hospital /ID# 247436
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0925
      • Takanoko Hospital /ID# 245658
  • Fukui
    • Fukui-shi, Fukui, Japan, 918-8503
      • Fukuiken Saiseikai Hospital /ID# 245662
  • Fukuoka
    • Kasuga-shi, Fukuoka, Japan, 816-0802
      • Jinnouchi Neurosurgical Clinic /ID# 245510
    • Kasuga-shi, Fukuoka, Japan, 816-0824
      • Ikeda Neurosurgical Clinic /ID# 245881
  • Gunma
    • Ota-shi, Gunma, Japan, 373-8585
      • SUBARU Health Insurance Society Ota Memorial Hospital /ID# 247948
  • Hiroshima
    • Hiroshima, Hiroshima, Japan, 730-8518
      • Hiroshima City Hiroshima Citizens Hospital /ID# 246683
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0003
      • Higashi Sapporo Neurology And Neurosurgery Clinic /ID# 245667
    • Sapporo, Hokkaido, Japan, 060-8570
      • Nakamura Memorial Hospital /ID# 247379
  • Hyōgo
    • Kobe, Hyōgo, Japan, 658-0064
      • Konan Medical Center /ID# 245557
    • Nishinomiya-shi, Hyōgo, Japan, 663-8014
      • Nishinomiya Municipal Central Hospital /ID# 246571
    • Nishinomiya-shi, Hyōgo, Japan, 663-8204
      • Yamaguchi Clinic /ID# 246370
  • Ibaraki
    • Mito, Ibaraki, Japan, 310-0015
      • Mito Kyodo General Hospital /ID# 245487
    • Tsukuba, Ibaraki, Japan, 305-0822
      • Tsukuba Neurosurgery/Headache Clinic /ID# 254665
  • Ishikawa-ken
    • Kahoku-gun, Ishikawa-ken, Japan, 929-0342
      • Kijima Neurosurgery Clinic /ID# 245758
    • Nonoichi-shi, Ishikawa-ken, Japan, 921-8841
      • Kanazawa Neurosurgical Hospital /ID# 254210
  • Kagawa-ken
    • Takamatsu, Kagawa-ken, Japan, 769-0103
      • Kokubu Clinic /ID# 245810
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital /ID# 245971
    • Kawasaki-shi, Kanagawa, Japan, 211-8588
      • Fujitsu Clinic /ID# 245811
  • Kochi
    • Kochi, Kochi, Japan, 780-0051
      • Atago Hospital /ID# 245818
    • Kochi, Kochi, Japan, 780-8011
      • Umenotsuji Clinic /ID# 246103
  • Kumamoto
    • Kumamoto, Kumamoto, Japan, 861-4101
      • Saiseikai Kumamoto Hospital /Id# 253546
  • Miyagi
    • Sendai, Miyagi, Japan, 981-3126
      • Narikawa Neurological Clinic /ID# 254023
    • Sendai, Miyagi, Japan, 982-0014
      • Sendai Headache and Neurology Clinic Medical Corporation /ID# 245664
  • Oita Prefecture
    • Ōita, Oita Prefecture, Japan, 8700831
      • Ooba Clinic for Neurosurgery & Headache /ID# 246201
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 700-0964
      • Makabe Clinic /ID# 246621
    • Okayama, Okayama-ken, Japan, 700-8557
      • Okayama City General Medical Center /ID# 246007
  • Osaka
    • Osaka, Osaka, Japan, 532-0003
      • Gokeikai Osaka Kaisei Hospital /ID# 246623
    • Osaka, Osaka, Japan, 555-0034
      • Chibune General Hospital /ID# 245973
    • Osaka, Osaka, Japan, 5560015
      • Tominaga Clinic /ID# 245812
    • Toyonaka-shi, Osaka, Japan, 560-0012
      • Takase Internal Medicine Clinic /ID# 245532
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital /ID# 245663
    • Tokorozawa-shi, Saitama, Japan, 359-1141
      • Saino Clinic /ID# 245921
  • Shizuoka
    • Shizuoka, Shizuoka, Japan, 420-0853
      • Japanese Red Cross Shizuoka Hospital /ID# 246204
  • Tochigi
    • Mibu, Tochigi, Japan, 321-0293
      • Dokkyo Medical University Hospital /ID# 246472
  • Tokyo
    • Hachioji-shi, Tokyo, Japan, 192-0032
      • Tokai University Hachioji Hospital /ID# 248326
    • Minato-ku, Tokyo, Japan, 108-8642
      • Kitasato University Kitasato Institute Hospital /ID# 246470
    • Setagaya-ku, Tokyo, Japan, 156-0043
      • Usuda Clinic Of Internal Medicine /ID# 246166
    • Shibuya-ku, Tokyo, Japan, 151-0051
      • Tokyo Headache Clinic /ID# 245486
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital /ID# 245660
    • Tachikawa-shi, Tokyo, Japan, 190-0001
      • Suzuki Kei Yasuragi Clinic /ID# 253493
  • Toyama
    • Toyama, Toyama, Japan, 930-0803
      • Sakura neuro Clinic /ID# 248320
  • Yamagata
    • Tendo-shi, Yamagata, Japan, 994-0083
      • Tendo Brain Clinic /ID# 246205
  • Yamanashi
    • Kai, Yamanashi, Japan, 400-0124
      • Nagaseki Headache Clinic /ID# 245485

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least a 1-year history of migraine (with or without aura).
• Less than 50 years of age at the time of migraine onset.
• History of 4 to 14 migraine days per month in the 3 months prior to screening.
• 4 to 14 migraine days in the baseline period and completed at least 20 out of 28 days at the baseline period per the eDiary.

Exclusion Criteria:

• Difficulty with distinguishing migraine headaches from tension-type or other headaches.
• Clinically significant hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atogepant Dose A; Participants will receive atogepant dose A once daily (QD) for 24 weeks.	Drug: Atogepant; Oral Tablet; Other Names: Qulipta
Experimental: Atogepant Dose B; Participants will receive atogepant dose B QD for 24 weeks.	Drug: Atogepant; Oral Tablet; Other Names: Qulipta
Experimental: Atogepant Dose C; Participants will receive atogepant dose C QD for 24 weeks.	Drug: Atogepant; Oral Tablet; Other Names: Qulipta
Experimental: Placebo; Participants will receive placebo QD for 12 weeks. Participants will be re-randomized at week 12 to receive atogepant dose A, dose B or dose C QD for 12 weeks.	Drug: Atogepant; Oral Tablet; Other Names: Qulipta; Drug: Placebo for Atogepant; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Migraine Days	Participants recorded daily duration of migraine in an eDiary. 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 eDiary divided by total number of days with eDiary 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 Measure (MMRM) was used for analysis.	Up to Week 12
Number of Participants Experiencing 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.	Up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the Activity Impairment in Migraine - Diary (AIM-D)	The AIM-D is an 11-item daily diary measure that assesses the impact of migraine and is comprised of two domains that evaluate performance of daily activities (7 items) and physical impairment (4 items). Participants are asked to rate the level of difficulty experienced in the past 24 hours with performance of daily activities and physical impairment using a 6 point rating scale ranging from "Not difficult at all" to "I could not do it at all." Scores range from 0-100 scale, with higher scores indicating greater impact of migraine.	Up to Week 12
Change From Baseline in Mean Monthly Physical Impairment Domain Score of the AIM-D	The AIM-D is an 11-item daily diary measure that assesses the impact of migraine and is comprised of two domains that evaluate performance of daily activities (7 items) and physical impairment (4 items). Participants are asked to rate the level of difficulty experienced in the past 24 hours with performance of daily activities and physical impairment using a 6 point rating scale ranging from "Not difficult at all" to "I could not do it at all." Scores range from 0-100 scale, with higher scores indicating greater impact of migraine.	Up to Week 12
Change From Baseline in Mean Monthly Headache Days	Participants recorded daily total duration of a headache in an eDiary. 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 eDiary divided by the total number of days with eDiary 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.	Up to Week 12
Change From Baseline in Mean Monthly Acute Medication Use Days	Participants recorded allowed medication(s) to treat an acute migraine in the daily eDiary. The monthly (4-week) acute medication use days was defined as the total number of reported acute medication use days in the eDiary divided by the total number of days with eDiary 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.	Up to Week 12
Percentage of Participants Achieving At Least 50% Reduction in the 3-month Average of Monthly Migraine Days	Participants recorded daily duration of migraine in an eDiary. 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 eDiary divided by total number of days with eDiary records in each 4-week period multiplied by 28. Each 4-week period was averaged.	Up to Week 12
Change From Baseline in Migraine Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score	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.	Up to Week 12

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Matsumori Y, Yamada H, Nagaseki Y, Shimizu K, Nagy K, Matsuzawa R, Otani T, He MY, Guo H, Ahmadyar G, Takeshima T. Atogepant for the preventive treatment of episodic migraine in Japanese participants: A phase 2/3, randomized, double-blind, placebo-controlled trial with an active treatment extension (RELEASE). Cephalalgia. 2025 Sep;45(9):3331024251374569. doi: 10.1177/03331024251374569. Epub 2025 Sep 26.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2023
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Migraine; Episodic Migraine; Atogepant
• 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: M22-056

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

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.: Yes