Efficacy, Safety, and Tolerability of Atogepant for the Prevention of Chronic Migraine

Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days were 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 is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from Mixed-effects model for repeated measures (MMRM) was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB 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. The monthly (4-week) migraine days were 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 is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from Mixed-effects model for repeated measures (MMRM) was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline to Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment.

An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were 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 is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB treatment period.

An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were 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 is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline to Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment.

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 pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. 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 is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB 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 pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. 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 is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline to Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment.

The AIM-D is a 11-item patient-reported outcome (PRO) measure that assesses the impact of migraine on the performance of daily activities which include, 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head 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). A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB treatment period. Overall number analyzed are the number of participants with data available for analyses.

The AIM-D is a 11-item PRO measure that assesses the impact of migraine on the performance of daily activities which includes 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head 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). A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB treatment period. Overall number analyzed are the number of participants with data available for analyses.

The 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 3 domains: Role Function Restrictive (question numbers 1-7, score ranges 7 to 42) assesses how migraines limit one's daily social and work-related activities; Role Function Preventive (question numbers 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the Emotional Function (question numbers 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale ranging from none of the time to 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 indicate better quality of life. A contrast from MMRM was used to obtain the average treatment effects across the 12-week treatment period.

Time frame: At Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment. Overall number analyzed are the number of participants with data available for analyses.

HIT-6 is a 6-question assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home, and in social situations. It assesses the effect that headaches have on normal daily life and the participant's ability to function. Responses are based on frequency using a 5-point scale ranging from never to always. The HIT-6 total score, which ranges from 36 to 78, is the sum of the responses - each of which is assigned a score ranging from 6 points (never) to 13 points (always). MMRM was used for the analyses.

Time frame: At Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment. Overall number analyzed are the number of participants with data available for analyses.

Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50 percent reduction from baseline 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. 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. The values are rounded off to the first decimal value.

Time frame: Baseline 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 (Weeks 1 to 4, 5 to 8, and 9 to 12) of eDiary data during the DB treatment period.

Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50 percent reduction from baseline 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. 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. The values are rounded off to the first decimal value.

Time frame: Baseline to Week 12

Population: Off-treatment hypothetical estimand population included all randomized participants who received ≥ 1 dose of study intervention, had an evaluable baseline period of eDiary data and had ≥ 1 evaluable postbaseline 4-week period (Weeks 1 to 4, 5 to 8, 9 to 12) of eDiary data during the study, regardless of whether on study treatment or off study treatment.