Trial Outcomes & Findings for Efficacy and Tolerability of Rimegepant for the Prevention of Migraine in Adults With History of Inadequate Response to Oral Preventive Medications (NCT NCT05518123)

A total of 962 participants signed the informed consent form and were enrolled in the study. Of the enrolled participants, 658 participants were randomized in the study and 304 were not randomized (due to failure to meet eligibility criteria at screening \[282 participants\], withdrawal of consent \[21 participants\], or adverse event \[1 participant\]).

Here "Number Analyzed" signifies number of participants evaluable for this baseline characteristic.

A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days.

Moderate or severe MD: a MD of moderate or severe headache pain intensity. MD: any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. Qualified migraine headache: migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of moderate or severe MD per month were prorated to 28 days and derived from data in the on-DBT efficacy analysis period as follows: 28\*(total number of moderate or severe MD through Month 3 \[Weeks 1 to 12\])/(total number of e-diary efficacy data days through Month 3 \[Weeks 1 to 12\]).

A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days.

A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days.

MSQ version 2.1 was a self-administered, 14-item instrument validated in 3 domains: role function-restrictive (7 items), role function-preventive (4 items), emotional function (3 items). The restrictive role function domain consisted of 7 items that described how migraine limited one's daily social and work-related activities. Each item was scored on a 6-point scale ranging from 1 to 6, where "1: none of the time," "2: a little bit of the time," "3: some of the time," "4: a good bit of the time," "5: most of the time," and "6: all of the time,". Item scores were recoded using (7 - original score). Raw dimension scores for restrictive role function domain were computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that lower score (0) indicated poor quality of life and higher scores (100) indicated better quality of life.

MIBS was a 4-item self-administered questionnaire that measures: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Each item was rated on a 6-point scale as: don't know/ not applicable; never; rarely; some of the time; much of the time; most or all of the time. The MIBS score was the weighted sum of the item scores and ranged from 0 to 12. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks.

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 did not necessarily have a causal relationship with this treatment. AE intensity included mild, moderate and severe, where Mild: usually transient and required only minimal treatment or therapeutic intervention. Event did not generally interfere with usual activities of daily living. Moderate: usually alleviated with additional specific therapeutic intervention. Event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to participant. Severe: interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. Participants were counted once in each intensity category based on greatest intensity of unique adverse event preferred terms.

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 did not necessarily have a causal relationship with this treatment. AE intensity included mild, moderate and severe, where Mild: usually transient and required only minimal treatment or therapeutic intervention. Event did not generally interfere with usual activities of daily living. Moderate: usually alleviated with additional specific therapeutic intervention. Event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to participant. Severe: interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. Participants were counted once in each intensity category based on greatest intensity of unique adverse event preferred terms.

A serious adverse event (SAE) was any event that met any of the following criteria at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect in the offspring who received rimegepant and other important medical events.

A SAE was any event that met any of the following criteria at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect in the offspring who received rimegepant and other important medical events.

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 did not necessarily have a causal relationship with this treatment. In this outcome measure, participants with AEs leading to discontinuation of study drug were reported.

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 did not necessarily have a causal relationship with this treatment. In this outcome measure, participants with AEs leading to discontinuation of study drug were reported.

Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1. Only those Grade 3 or 4 laboratory tests with non-zero values in any of treatment arms are reported in this outcome measure.

Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to NCI CTCAE v5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1. Only those Grade 3 or 4 laboratory tests with non-zero values in any of treatment arms are reported in this outcome measure.

A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days and derived from data in the on-DBT efficacy analysis period as follows: 28\*(total number of migraine days through Month 3 \[Weeks 1 to 12\])/(total number of e-diary efficacy data days through Month 3 \[Weeks 1 to 12\]).

An acute migraine-specific medication day was defined as any calendar day during which a participant took a migraine-specific acute migraine medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. The number of acute migraine-specific medication days per month were prorated to 28 days.

MIBS was a 4-item self-administered questionnaire that measures: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Each item was rated on a 6-point scale as: don't know/ not applicable; never; rarely; some of the time; much of the time; most or all of the time. The MIBS score was the weighted sum of the item scores and ranged from 0 to 12. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks.

MSQ was a self-administered, 14-item instrument validated in 3 domains: role function-restrictive (7 items), role function-preventive (4 items), emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 to 6, where "1: none of the time," "2: a little bit of the time," "3: some of the time," "4: a good bit of the time," "5: most of the time," and "6: all of the time,". Item scores were recoded using (7 - original score). Raw domain scores are computed as a sum of item responses and rescaled to a 0 to 100 scale such that lower score (0) indicated poor quality of life and higher scores (100) indicated better quality of life.

MFIQ was a 26-item participant-report questionnaire. It is designed to measure the subjective impact of migraine on physical, social, and emotional functioning over 5 domains: physical function (5 items), usual activities (10 items), social function (5 items), emotional function (5 items) and overall impact on usual activities (16 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the past 7 days.

The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The absenteeism score was calculated from Q2 and Q4 for participants who responded "yes" to Q1 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity.

The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The presenteeism score was calculated using Q5 for participants who responded "yes" to Q1 and had Q4\>0 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity.

The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The work productivity loss score was calculated using Q2, Q4, and Q5 for participants who responded "yes" to Q1 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity.

The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The activity impairment score was calculated using Q6 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity.

The PGA scale was a single item assessment that measured the participant's overall assessment of migraine on a 5-point scale as: (1) very good: asymptomatic and no limitation of normal activities; (2) good: mild symptoms and no limitation of normal activities; (3) fair: moderate symptoms and limitation of some normal activities; (4) poor: severe symptoms and inability to carry out most normal activities; (5) very poor: very severe symptoms which are intolerable and inability to carry out all normal activities. Lower scores indicated fewer symptoms and less disability to carry out normal activities.