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

• ClinicalTrials.gov Identifier: NCT03777059
• Recruitment Status: Completed
• First Posted: December 17, 2018
• Results First Posted: July 9, 2021
• Last Update Posted: July 9, 2021
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Tracking Information

• First Submitted Date: December 13, 2018
• First Posted Date: December 17, 2018
• Results First Submitted Date: June 18, 2021
• Results First Posted Date: July 9, 2021
• Last Update Posted Date: July 9, 2021
• Actual Study Start Date: December 14, 2018
• Actual Primary Completion Date: June 19, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 18, 2021)

Change From Baseline in Mean Monthly Migraine Days Across the 12-Week Treatment Period [ Time Frame: Baseline (Day -28 to Day -1) to Week 12 ]

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.

Original Primary Outcome Measures (submitted: December 13, 2018)

Change from baseline in mean monthly migraine days across the 12-week treatment period [ Time Frame: 12 weeks ]

Baseline is defined as the number of migraine days during the last 28 days of the baseline phase, ie, Day -28 to -1.

Current Secondary Outcome Measures (submitted: June 18, 2021)

• Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period [ Time Frame: Baseline (Day-28 to Day -1) to Week 12 ]
  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.
• Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period [ Time Frame: Baseline (Day-28 to Day -1) to Week 12 ]
  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.
• Percentage of Participants With at Least a 50% Reduction (Improvement) in 3-month Average of Monthly Migraine Days [ Time Frame: Baseline (Day -28 to Day -1) to Week 12 ]
  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.
• Change From Baseline in Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score at Week 12 [ Time Frame: Baseline (Day 1) to 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.
• 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 [ Time Frame: Baseline (Day -28 to Day -1) to Week 12 ]
  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.
• 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 [ Time Frame: Baseline (Day -28 to Day -1) to Week 12 ]
  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.

Original Secondary Outcome Measures (submitted: December 13, 2018)

• Change from baseline in mean monthly headache days across the 12-week treatment period. [ Time Frame: 12 Weeks ]
  Baseline is defined as the number of migraine days during the last 28 days of the baseline phase, ie, Day -28 to -1.
• Change from baseline in mean monthly acute medication use days across the 12-week treatment period. [ Time Frame: 12 weeks ]
  Baseline is defined as the number of acute medication use days during the last 28 days of the baseline phase, ie, Day-28 to -1.
• Proportion of participants with at least a 50% reduction in mean monthly migraine days across the 12-week treatment period. [ Time Frame: 12 weeks ]
  Defined as participants with at least a 50% reduction from baseline in monthly migraine days,
• Change from baseline in mean monthly performance of daily activities domain score of the AIM-D across the 12-week treatment period. [ Time Frame: 12 weeks ]
  Baseline is defined as the monthly performance of daily activities domain score during the last 28 days of the baseline phase, ie, Day -28 to -1. The Activity Impairment in Migraine - Diary (AIM-D) is a 9-item Patient Reported Outcome (PRO) measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale ranging from "Not difficult at all," "A little difficult," "Somewhat difficult," "Verydifficult," "Extremely difficult," and "I could not do it at all."
• Change from baseline in mean monthly physical impairment domain score of the AIM-D across the 12-week treatment period. [ Time Frame: 12 weeks ]
  Baseline is defined as the monthly physical impairment domain score during the last 28 days of the baseline phase, ie, Day -28 to -1. The Activity Impairment in Migraine - Diary (AIM-D) is a 9-item Patient Reported Outcome (PRO) measure that assesses the impact of migraine on the performance of daily activities and physical impairment using a 6-point rating scale ranging from "Not difficult at all," "A little difficult," "Somewhat difficult," "Verydifficult," "Extremely difficult," and "I could not do it at all."

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 12-Week Placebo-controlled Study of Atogepant for the Preventive Treatment of Migraine in Participants With Episodic Migraine
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Episodic Migraine

Intervention

• Drug: Atogepant
  Atogepant tablet
• Drug: Placebo
  Placebo-matching atogepant tablets

Study Arms

• Placebo Comparator: Placebo
  Placebo-matching atogepant tablets orally once daily for 12 weeks.
  Intervention: Drug: Placebo
• Experimental: Atogepant 10 mg
  Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo
• Experimental: Atogepant 30 mg
  Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo
• Experimental: Atogepant 60 mg
  Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
  Interventions:

  • Drug: Atogepant
  • Drug: Placebo

Publications *

• Lipton RB, Pozo-Rosich P, Blumenfeld AM, 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. 2023 Feb 21;100(8):e764-e777. doi: 10.1212/WNL.0000000000201568. Epub 2022 Nov 17.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 10, 2020): 910
• Original Estimated Enrollment (submitted: December 13, 2018): 872
• Actual Study Completion Date: June 19, 2020
• Actual Primary Completion Date: June 19, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03777059
• Other Study ID Numbers: 3101-301-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Allergan
• Original Responsible Party: Same as current
• Current Study Sponsor: Allergan
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Joel Trugman, MD; Allergan

• PRS Account: Allergan
• Verification Date: June 2021