Trial Outcomes & Findings for 12-Week Placebo-controlled Study of Atogepant for the Preventive Treatment of Migraine in Participants With Episodic Migraine (NCT NCT03777059)

Last Updated: 2021-07-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

910 participants

Primary outcome timeframe

Baseline (Day -28 to Day -1) to Week 12

Results posted on

2021-07-09

Participant Flow

Participants diagnosed with episodic migraine were enrolled in one of 4 treatment arms: placebo, or atogepant 10 mg once daily (QD), 30 mg QD, 60 mg QD in Double-blind (DB) Treatment Period.

Participant milestones

Participant milestones
Measure	Placebo Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
DB Treatment Period (Up to Week 12) STARTED	223	222	230	235
DB Treatment Period (Up to Week 12) Treated: Safety Population	222	221	228	231
DB Treatment Period (Up to Week 12) COMPLETED	201	193	207	204
DB Treatment Period (Up to Week 12) NOT COMPLETED	22	29	23	31
Follow-Up Period (Weeks 12 to 16) STARTED	46	54	38	45
Follow-Up Period (Weeks 12 to 16) COMPLETED	41	49	32	36
Follow-Up Period (Weeks 12 to 16) NOT COMPLETED	5	5	6	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
DB Treatment Period (Up to Week 12) Adverse Event	6	9	4	6
DB Treatment Period (Up to Week 12) Lack of Efficacy	1	0	0	1
DB Treatment Period (Up to Week 12) Withdrawal by Subject	8	9	8	10
DB Treatment Period (Up to Week 12) Lost to Follow-up	3	3	4	5
DB Treatment Period (Up to Week 12) Pregnancy	0	1	0	0
DB Treatment Period (Up to Week 12) Protocol Deviation	4	5	7	8
DB Treatment Period (Up to Week 12) Reason Not Specified	0	2	0	1
Follow-Up Period (Weeks 12 to 16) Withdrawal by Subject	5	3	4	5
Follow-Up Period (Weeks 12 to 16) Lost to Follow-up	0	1	0	3
Follow-Up Period (Weeks 12 to 16) Protocol Deviation	0	1	1	0
Follow-Up Period (Weeks 12 to 16) Reason Not Specified	0	0	1	1

Baseline Characteristics

mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=222 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=221 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=228 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=231 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Total n=902 Participants Total of all reporting groups
Age, Continuous	40.3 years STANDARD_DEVIATION 12.81 • n=222 Participants	41.4 years STANDARD_DEVIATION 12.05 • n=221 Participants	42.1 years STANDARD_DEVIATION 11.68 • n=228 Participants	42.5 years STANDARD_DEVIATION 12.41 • n=231 Participants	41.6 years STANDARD_DEVIATION 12.25 • n=902 Participants
Sex: Female, Male Female	198 Participants n=222 Participants	200 Participants n=221 Participants	204 Participants n=228 Participants	199 Participants n=231 Participants	801 Participants n=902 Participants
Sex: Female, Male Male	24 Participants n=222 Participants	21 Participants n=221 Participants	24 Participants n=228 Participants	32 Participants n=231 Participants	101 Participants n=902 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=222 Participants	1 Participants n=221 Participants	1 Participants n=228 Participants	1 Participants n=231 Participants	3 Participants n=902 Participants
Race (NIH/OMB) Asian	2 Participants n=222 Participants	2 Participants n=221 Participants	1 Participants n=228 Participants	7 Participants n=231 Participants	12 Participants n=902 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=222 Participants	0 Participants n=221 Participants	0 Participants n=228 Participants	0 Participants n=231 Participants	0 Participants n=902 Participants
Race (NIH/OMB) Black or African American	24 Participants n=222 Participants	34 Participants n=221 Participants	38 Participants n=228 Participants	28 Participants n=231 Participants	124 Participants n=902 Participants
Race (NIH/OMB) White	194 Participants n=222 Participants	181 Participants n=221 Participants	185 Participants n=228 Participants	192 Participants n=231 Participants	752 Participants n=902 Participants
Race (NIH/OMB) More than one race	2 Participants n=222 Participants	3 Participants n=221 Participants	3 Participants n=228 Participants	2 Participants n=231 Participants	10 Participants n=902 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=222 Participants	0 Participants n=221 Participants	0 Participants n=228 Participants	1 Participants n=231 Participants	1 Participants n=902 Participants
Race/Ethnicity, Customized Hispanic	23 Participants n=222 Participants	21 Participants n=221 Participants	19 Participants n=228 Participants	14 Participants n=231 Participants	77 Participants n=902 Participants
Race/Ethnicity, Customized Non-Hispanic	199 Participants n=222 Participants	200 Participants n=221 Participants	209 Participants n=228 Participants	217 Participants n=231 Participants	825 Participants n=902 Participants
Monthly Migraine Days	7.5 migraine days per month STANDARD_DEVIATION 2.39 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	7.5 migraine days per month STANDARD_DEVIATION 2.46 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	7.9 migraine days per month STANDARD_DEVIATION 2.32 • n=223 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	7.8 migraine days per month STANDARD_DEVIATION 2.31 • n=222 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	7.6 migraine days per month STANDARD_DEVIATION 2.37 • n=873 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Monthly Headache Days	8.4 headache days per month STANDARD_DEVIATION 2.55 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	8.4 headache days per month STANDARD_DEVIATION 2.75 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	8.8 headache days per month STANDARD_DEVIATION 2.62 • n=223 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	9.0 headache days per month STANDARD_DEVIATION 2.56 • n=222 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	8.7 headache days per month STANDARD_DEVIATION 2.63 • n=873 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
Monthly Acute Medication Use	6.5 acute medication use days per month STANDARD_DEVIATION 3.15 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	6.6 acute medication use days per month STANDARD_DEVIATION 2.99 • n=214 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	6.7 acute medication use days per month STANDARD_DEVIATION 3.02 • n=223 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	6.9 acute medication use days per month STANDARD_DEVIATION 3.17 • n=222 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.	6.7 acute medication use days per month STANDARD_DEVIATION 3.08 • n=873 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.
MSQ v2.1 Role Function-Restrictive Domain Score	46.8 score on a scale STANDARD_DEVIATION 19.67 • n=213 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	44.9 score on a scale STANDARD_DEVIATION 21.37 • n=212 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	44.0 score on a scale STANDARD_DEVIATION 19.61 • n=222 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	46.8 score on a scale STANDARD_DEVIATION 20.36 • n=222 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	45.6 score on a scale STANDARD_DEVIATION 20.26 • n=869 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.
Daily Activities Domain Score of the Activity Impairment in Migraine- Diary (AIM-D)	15.2 score on a scale STANDARD_DEVIATION 8.25 • n=188 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	15.5 score on a scale STANDARD_DEVIATION 8.85 • n=191 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	16.9 score on a scale STANDARD_DEVIATION 8.02 • n=188 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	15.9 score on a scale STANDARD_DEVIATION 8.34 • n=192 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	15.9 score on a scale STANDARD_DEVIATION 8.38 • n=759 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.
Monthly Physical Impairment Domain Score of the AIM-D	11.2 score on a scale STANDARD_DEVIATION 8.11 • n=188 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	11.7 score on a scale STANDARD_DEVIATION 8.46 • n=191 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	13.0 score on a scale STANDARD_DEVIATION 8.00 • n=188 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	11.6 score on a scale STANDARD_DEVIATION 7.85 • n=192 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.	11.9 score on a scale STANDARD_DEVIATION 8.12 • n=759 Participants • mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period. Number analyzed is the number of participants available for the analyses at Baseline.

PRIMARY outcome

Timeframe: Baseline (Day -28 to Day -1) to Week 12

Population: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period of eDiary data, and had at least 1 evaluable post-baseline 4-week period of eDiary data during the Double-blind Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=214 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=223 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=222 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Change From Baseline in Mean Monthly Migraine Days Across the 12-Week Treatment Period	-2.48 migraine days per month Standard Error 0.210	-3.69 migraine days per month Standard Error 0.210	-3.86 migraine days per month Standard Error 0.206	-4.20 migraine days per month Standard Error 0.206

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=214 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=223 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=222 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Change From Baseline in Mean Monthly Headache Days Across the 12-Week Treatment Period	-2.52 headache days per month Standard Error 0.225	-3.94 headache days per month Standard Error 0.225	-4.04 headache days per month Standard Error 0.221	-4.23 headache days per month Standard Error 0.221

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=214 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=223 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=222 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-Week Treatment Period	-2.35 acute medication use days per month Standard Error 0.184	-3.66 acute medication use days per month Standard Error 0.183	-3.68 acute medication use days per month Standard Error 0.180	-3.85 acute medication use days per month Standard Error 0.180

SECONDARY outcome

Timeframe: Baseline (Day -28 to Day -1) to Week 12

Population: mITT Population included all randomized participants who received at least 1 dose of study intervention, had an evaluable Baseline period (Day -28 to Day -1) of eDiary data, and had at least 1 evaluable post-baseline 4-week period (Weeks 1-4, 5-8, and 9-12) of eDiary data during the Double-blind Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=214 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=223 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=222 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Percentage of Participants With at Least a 50% Reduction (Improvement) in 3-month Average of Monthly Migraine Days	29.0 percentage of participants	55.6 percentage of participants	58.7 percentage of participants	60.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=198 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=186 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=203 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=201 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Change From Baseline in Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Role Function-Restrictive Domain Score at Week 12	20.45 score on a scale Standard Error 1.617	30.35 score on a scale Standard Error 1.639	30.53 score on a scale Standard Error 1.593	31.25 score on a scale Standard Error 1.591

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=178 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=182 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=181 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=178 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
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	-6.09 score on a scale Standard Error 0.504	-7.28 score on a scale Standard Error 0.500	-8.63 score on a scale Standard Error 0.502	-9.41 score on a scale Standard Error 0.504

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=178 Participants Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=182 Participants Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=181 Participants Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=178 Participants Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
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	-4.03 score on a scale Standard Error 0.439	-5.11 score on a scale Standard Error 0.436	-6.02 score on a scale Standard Error 0.438	-6.49 score on a scale Standard Error 0.439

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Atogepant 10 mg

Serious events: 2 serious events

Other events: 34 other events

Deaths: 0 deaths

Atogepant 30 mg

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Atogepant 60 mg

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=222 participants at risk Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=221 participants at risk Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=228 participants at risk Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=231 participants at risk Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.45% 1/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Nervous system disorders Brain injury	0.45% 1/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Nervous system disorders Optic neuritis	0.00% 0/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.45% 1/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.45% 1/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Respiratory, thoracic and mediastinal disorders Negative pressure pulmonary oedema	0.45% 1/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.

Other adverse events

Other adverse events
Measure	Placebo n=222 participants at risk Placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 10 mg n=221 participants at risk Atogepant 10 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 30 mg n=228 participants at risk Atogepant 30 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.	Atogepant 60 mg n=231 participants at risk Atogepant 60 mg tablet orally once daily and placebo-matching atogepant tablets orally once daily for 12 weeks.
Gastrointestinal disorders Constipation	0.45% 1/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	7.7% 17/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	7.0% 16/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	6.9% 16/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Gastrointestinal disorders Nausea	1.8% 4/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	5.0% 11/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	4.4% 10/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	6.1% 14/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Infections and infestations Upper respiratory tract infection	4.5% 10/222 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	4.1% 9/221 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	5.7% 13/228 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	3.9% 9/231 • From first dose of study drug through end of study (Up to 16 weeks) All-Cause Mortality is reported for all randomized participants. Safety Population, all participants who received at least 1 dose of study intervention, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER