Study of BOTOX Injections in Prevention of Migraine in Adult Participants With Episodic Migraine

Primary Outcome Measures

1. Change From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6
   The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.
2. Number of Participants With Treatment-Emergent 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. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Secondary Outcome Measures

1. Change From Baseline in the Frequency of Monthly Headache Days Across Months 5 and 6
   The frequency of monthly headache days across Months 5 and 6 is calculated by taking the 2-month average of monthly headache days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.
2. Percentage of Participants With ≥ 50% Reduction From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6
   The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. The responder status of 50% reduction from Baseline is defined as a participant with at least a 50% reduction from Baseline in the 2-month average of monthly migraine days over Months 5 and 6.
3. Change From Baseline in the Frequency of Monthly Acute Headache Medication Days Across Months 5 and 6
   Monthly acute headache medication days across Months 5 and 6 is calculated by taking the 2-month average of monthly acute headache medication days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.
4. Change From Baseline in Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) Role Function - Restrictive (RFR) Domain Score At Month 6
   The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine over the past 4 weeks. It is divided into 3 domains, and the Role Function Restrictive (RFR) assesses how migraines limit one's daily social and work-related activities 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. Positive changes from Baseline indicate improvement.
5. Change From Baseline in the Activity Impairment in Migraine - Diary (AIM-D) Physical Impairment Domain Score Across Months 5 and 6
   AIM-D Physical Impairment Domain score is calculated based on the summation of AIM-D items 6-9. Participants answer each question based on the level of difficulty experienced in the 24 hours prior, with "during your headache" indicated for when they reported a headache, using a 6-point rating scale ranging from "not difficult at all" to "extremely difficult". The raw daily score is transformed to a 0-100 scale, and the monthly score is calculated using the average daily scores, where a higher score indicates worse physical impairment. AIM-D Physical Impairment domain score across Months 5 and 6 is calculated by taking the 2-month average of AIM-D Physical Impairment domain scores over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.
6. Change From Baseline in the Total 6-item Headache Impact Test (HIT-6) Score Across Months 5 and 6
   The HIT-6 is a 6-item 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 subject'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). The Total 6-item Headache Impact Test (HIT-6) score across Months 5 and 6 is calculated by taking the 2-month average of total 6-item Headache Impact Test (HIT-6) scores over Months 5 and 6. Negative changes from Baseline in the HIT-6 score indicate improvement.