A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention

A migraine day was defined as any calendar day in which participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was defined as migraine with or without aura, lasting for greater than or equal to (>=) 30 minutes, and met at least one of following criteria (A and/or B): A. >=2 of following pain features: a. Unilateral location, b. Pulsating quality (throbbing), c. Moderate or severe pain intensity, d. Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs) B. >= 1 of the following associated symptoms: a. Nausea and/or vomiting b. Photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived as follows: 28*(total number of migraine days through Month 3[Weeks 1 to 12] in the on-DBT efficacy analysis period)/ (total number of eDiary efficacy data days through Month 3[Weeks 1 to 12] in on-DBT efficacy analysis period).

A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for greater than or equal to (>=) 30 minutes, and met at least one of the following criteria (A and/or B): A.>=2 of the following pain features: a. Unilateral location, b. Pulsating quality (throbbing), c. Moderate or severe pain intensity, d. Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs) B. >= 1 of the following associated symptoms: a. Nausea and/or vomiting b. Photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived for month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28* (total number of migraine days in the month[Week 9 to 12])/(total number of eDiary efficacy data days in the month[Week 9 to 12]).

A migraine day was defined as any calendar day in which participant experienced a qualified migraine headache (onset, continuation or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for greater than or equal to (>=) 30 minutes, and met at least one of the following criteria (A and/or B): A. >=2 of the following pain features: a. Unilateral location, b. Pulsating quality (throbbing), c. Moderate or severe pain intensity, d. Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs) B. >= 1 of the following associated symptoms: a. Nausea and/or vomiting b. Photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived for month (i.e., 4-week interval) in the on-DBT efficacy analysis period as follows: 28* (total number of migraine days in the month[Week 1 to 4])/ (total number of eDiary efficacy data days in the month[Week 1 to 4]).

Acute migraine (AM)-specific medication day was defined as any calendar day on which the participant took an acute migraine-specific medication during aura or to treat a headache. Acute migraine-specific medications were triptans and ergotamine. The number of acute migraine-specific medication days per month were prorated to 28 days and derived as follows: 28 * (total number of acute migraine-specific medication days through Month 3 [Week 1 to 12] in the on-DBT efficacy analysis period)/ (total number of eDiary efficacy data days through Month 3 [Week 1 to 12] in the on-DBT efficacy analysis period).

MSQ v 2.1 is 14-item questionnaire that assessed impact of treatment on participant-reported quality of life across 3 domains: role function-restrictive, preventive, and emotional function. Restrictive role function domain consists of 7 items that describe how migraine limits one's daily social, work-related activities. Participants respond to items using a 6-point scale ranging from 1 (none of the time) to 6 (all of the time), which are assigned scores of 1 to 6, respectively. Response from each item of restrictive role function domain were added providing a possible raw score range of 7 (no impairment) to 42 (maximum impairment). Raw score range of restrictive role function domain was then transformed to a 0 (no impairment) to 100 (maximum impairment), higher scores = higher impairment.

MIDAS is a retrospective, participant-reported, 5-item questionnaire that measured headache related disability as lost days due to headache from paid work or school, household work and non-work activities over past 3-months. The total score is calculated as the sum of item scores to all 5 questions on a scale of 0 (no disability) to 90 (maximum disability) resulting into overall possible MIDAS total score (range from 0 (no disability) to 450 (maximum disability). Higher scores = more severe disability.

AEs: new untoward medical occurrence or worsening of a pre-existing medical condition in participant or clinical investigation participant administered investigational product that does not necessarily have a causal relationship with treatment. AEs included both SAEs and all non-SAEs. Severity: Moderate=Alleviated with additional specific therapeutic intervention, interfered with activities of daily living, causing discomfort, but possessed no significant or permanent risk of harm. Severe= Interrupted activities of daily living significantly affected clinical status or required intensive therapeutic intervention.

AEs: new untoward medical occurrence or worsening of a pre-existing medical condition in participant or clinical investigation participant administered investigational product that does not necessarily have a causal relationship with treatment. SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

Laboratory tests included eosinophils, hemoglobin, leukocytes, lymphocytes, neutrophils, platelets; albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate, bilirubin, calcium, cholesterol, potassium, sodium, triglycerides, uric acid, urinalysis, urine protein, creatine kinase (CK), creatinine, glomerular filtration rate (GFR), glucose, glucose fasting, lactate dehydrogenase, low density lipoprotein (LDL) Cholesterol, LDL Cholesterol. Number of participants with grade 3 to 4 laboratory test abnormalities were evaluated in this outcome measure. Only rows which included at least 1 participant in any reporting group with grade 3 to 4 abnormality were reported in this outcome measure. As per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) Grade 3= severe and Grade 4= life-threatening or disabling.

AEs: new untoward medical occurrence or worsening of a pre-existing medical condition in participant or clinical investigation participant administered investigational product that does not necessarily have a causal relationship with treatment. AEs included both SAEs and all non-SAEs. Severity: Moderate=Alleviated with additional specific therapeutic intervention, interfered with activities of daily living, causing discomfort, but possessed no significant or permanent risk of harm. Severe= Interrupted activities of daily living significantly affected clinical status or required intensive therapeutic intervention.

AEs: new untoward medical occurrence or worsening of a pre-existing medical condition in participant or clinical investigation participant administered investigational product that does not necessarily have a causal relationship with treatment. SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

Laboratory tests included eosinophils, hemoglobin, leukocytes, lymphocytes, neutrophils, platelets; albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate, bilirubin, calcium, cholesterol, potassium, sodium, triglycerides, uric acid, urinalysis, urine protein, creatine kinase (CK), creatinine, glomerular filtration rate (GFR), glucose, glucose fasting, lactate dehydrogenase, low density lipoprotein (LDL) Cholesterol, LDL Cholesterol. Number of participants with grade 3 to 4 laboratory test abnormalities were evaluated in this outcome measure. Only rows which included at least 1 participant in any reporting group with grade 3 to 4 abnormality were reported in this outcome measure. As per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) Grade 3= severe and Grade 4= life-threatening or disabling.

Elevations of AST or alanine aminotransferase (ALT) > 3 *upper limit of normal (ULN) concurrent with total bilirubin (TBL) > 2 *ULN (elevations on the same laboratory collection date) were included.

Elevations of AST or ALT > 3 * ULN concurrent with TBL > 2 *ULN were defined as elevations on the same collection date.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. AEs by intensity: Mild: Transient and may require only minimal treatment or therapeutic intervention. Event did not interfere with activities of daily living. Moderate: Alleviated with additional specific therapeutic intervention. Event interfered with activities of daily living, causing discomfort, but possessed no significant or permanent risk of harm. Severe: Interrupted activities of daily living significantly affected clinical status or required intensive therapeutic intervention.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. AEs by intensity: Mild: Transient and may require only minimal treatment or therapeutic intervention. Event did not interfere with activities of daily living. Moderate: Alleviated with additional specific therapeutic intervention. Event interfered with activities of daily living, causing discomfort, but possessed no significant or permanent risk of harm. Severe: Interrupted activities of daily living significantly affected clinical status or required intensive therapeutic intervention.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.