Migraine
Conditions
Keywords
Migraine Prevention, Phonophobia, Photophobia, Nausea
Brief summary
The purpose of this is study is to compare the efficacy of BHV-3500 (zavegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.
Interventions
DRUGBHV-3500 (zavegepant)
BHV-3500 (zavegepant) softgel capsule.
DRUGPlacebo
Matching placebo softgel capsule.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following: 1. Age of onset of migraines prior to 50 years of age 2. Migraine attacks, on average, lasting 4 - 72 hours if untreated 3. Per subject report, at least 15 headache days per month, at lest 8 migraine days per month, and at least 1 headache-free day per month within the last 3 months prior to the Screening Visit 4. Eight or more migraine days during the Observation Period 5. 15 or more headache days during the Observation Period 6. One or more non-headache days during the Observation Period 7. Ability to distinguish migraine attacks from tension/cluster headaches 8. Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study.
Exclusion criteria
1. Subject with a history of HIV disease 2. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening 3. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to screening). 4. Subjects with major depressive episode or anxiety disorder which require more than 1 daily medication for each disorder or subjects with a major depressive episode within the last 12 months. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening Visit. 5. Subjects with active chronic pain syndromes, other pain syndromes (including trigeminal neuralgia), psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion interfere with study assessments of safety or efficacy. 6. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease or condition (e.g. chronic pancreatitis, ulcerative colitis, etc.) that causes malabsorption. 7. Body mass index \> 33 kg/m2 8. History of gallstones or cholecystectomy. 9. The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | Observation Phase: 28 days prior to randomization and baseline; Entire DBT Phase: 12 weeks (Week 1 through 12) | A migraine day was defined as any calendar day in which participant experienced a qualified migraine headache (onset, continuation or recurrence of 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 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 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 on-DBT efficacy analysis period)/ (total number of eDiary efficacy data days through Month 3\[Weeks 1 to 12\] in the on-DBT efficacy analysis period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase | Observation Phase: 28 days prior to randomization and baseline; DBT Phase: last 4 weeks (Week 9 through 12) | 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\[Week 9 to 12\]). |
| Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase | Observation Phase: 28 days prior to randomization and baseline; DBT Phase: first 4 weeks (Week 1 through 4) | 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\[Week 1 to 4\]). |
| Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | Entire DBT Phase: 12 weeks (Week 1 through 12) | 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). |
| Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12 | DBT Phase: Baseline (before dose on Day 1), Week 12 | 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. |
| Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 | DBT Phase: Baseline (before dose on Day 1), Week 12 | 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. |
| Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | DBT Phase: During 12 weeks of treatment | 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. |
| Number of Participants With Serious Adverse Events (SAEs): DBT Phase | DBT Phase: During 12 weeks of treatment | 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. |
| Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | DBT Phase: During 12 weeks of 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. |
| Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | DBT: During 12 weeks of 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. |
| Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | Entire DBT Phase: 12 weeks (Week 1 through 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 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). |
| Number of Participants With SAEs: OLE Phase | OLE: During 52 weeks of treatment | 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. |
| Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase | OLE: During 52 weeks of 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. |
| Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | OLE: During 52 weeks of 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. |
| Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | DBT: Over 12 weeks of treatment | 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. |
| Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: OLE Phase | OLE: Over 52 weeks of treatment | Elevations of AST or ALT \> 3 \* ULN concurrent with TBL \> 2 \*ULN were defined as elevations on the same collection date. |
| Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | DBT Phase: During 12 weeks of 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. |
| Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | DBT Phase: During 12 weeks of 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. |
| Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | OLE: Over 52 weeks of 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. |
| Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: OLE Phase | OLE: Over 52 weeks of 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. |
| Number of Participants With Moderate or Severe AEs: OLE Phase | OLE: During 52 weeks of treatment | 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. |
Countries
United States
Participant flow
Pre-assignment details
The study enrolled 1753 participants, out of which 1219 were not randomized. Only 534 participants were randomized in a 12-week double-blind treatment (DBT) phase. A total of 298 eligible participants then entered in a 52-week open-label extension (OLE) phase. Participants had a follow-up of 8 weeks after discontinuation or completion of treatment in DBT (if not entered OLE) or OLE phase.
Participants by arm
| Arm | Count |
|---|---|
| Zavegepant 100 mg (DBT) Participants were randomized to receive Zavegepant 100 milligrams (mg) orally as soft gelatin capsules (25 mg \*4 capsules) daily for 12 weeks in DBT phase. | 173 |
| Zavegepant 200 mg (DBT) Participants were randomized to receive Zavegepant 200 mg orally as soft gelatin capsules (25 mg \*8 capsules) daily for 12 weeks in DBT phase. | 175 |
| Placebo (DBT) Matched to Zavegepant 100 mg Participants were randomized to receive placebo matched to Zavegepant 100 mg daily for 12 weeks in DBT phase. | 86 |
| Placebo (DBT) Matched to Zavegepant 200 mg Participants were randomized to receive placebo matched to Zavegepant 200 mg daily for 12 weeks in DBT phase. | 88 |
| Total | 522 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1: DBT Phase | Adverse Event | 1 | 5 | 3 | 4 |
| Period 1: DBT Phase | Death | 1 | 0 | 0 | 0 |
| Period 1: DBT Phase | Lost to Follow-up | 3 | 7 | 1 | 3 |
| Period 1: DBT Phase | Non-compliance | 1 | 0 | 1 | 2 |
| Period 1: DBT Phase | Other | 0 | 1 | 0 | 0 |
| Period 1: DBT Phase | Pregnancy | 2 | 0 | 0 | 0 |
| Period 1: DBT Phase | Randomized but not treated | 5 | 5 | 2 | 0 |
| Period 1: DBT Phase | Study terminated by sponsor | 15 | 16 | 5 | 9 |
| Period 1: DBT Phase | Withdrawal by Subject | 6 | 12 | 7 | 6 |
| Period 2: OLE Phase | Adverse Event | 3 | 4 | 2 | 0 |
| Period 2: OLE Phase | Failure to meet continuation criteria | 0 | 0 | 1 | 1 |
| Period 2: OLE Phase | Lost to Follow-up | 8 | 4 | 3 | 4 |
| Period 2: OLE Phase | Non-compliance | 2 | 2 | 0 | 1 |
| Period 2: OLE Phase | Not reported | 0 | 2 | 0 | 0 |
| Period 2: OLE Phase | Other | 0 | 2 | 0 | 0 |
| Period 2: OLE Phase | Physician Decision | 1 | 1 | 0 | 0 |
| Period 2: OLE Phase | Pregnancy | 0 | 0 | 2 | 0 |
| Period 2: OLE Phase | Study terminated by sponsor | 41 | 37 | 17 | 19 |
| Period 2: OLE Phase | Withdrawal by Subject | 16 | 8 | 3 | 7 |
| Period 3: Follow-up Phase | Lost to Follow-up | 5 | 9 | 0 | 1 |
| Period 3: Follow-up Phase | Not reported | 18 | 15 | 1 | 4 |
| Period 3: Follow-up Phase | Other | 0 | 1 | 2 | 1 |
| Period 3: Follow-up Phase | Withdrawal by Subject | 7 | 6 | 3 | 4 |
Baseline characteristics
| Characteristic | Zavegepant 100 mg (DBT) | Zavegepant 200 mg (DBT) | Placebo (DBT) Matched to Zavegepant 100 mg | Placebo (DBT) Matched to Zavegepant 200 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41.7 Years STANDARD_DEVIATION 12.85 | 43.2 Years STANDARD_DEVIATION 13.3 | 41.7 Years STANDARD_DEVIATION 13.15 | 41.5 Years STANDARD_DEVIATION 13.14 | 42.2 Years STANDARD_DEVIATION 13.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants | 47 Participants | 26 Participants | 27 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 128 Participants | 60 Participants | 61 Participants | 374 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 3 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 35 Participants | 16 Participants | 17 Participants | 103 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 130 Participants | 132 Participants | 66 Participants | 63 Participants | 391 Participants |
| Sex: Female, Male Female | 127 Participants | 144 Participants | 72 Participants | 70 Participants | 413 Participants |
| Sex: Female, Male Male | 46 Participants | 31 Participants | 14 Participants | 18 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 173 | 0 / 175 | 0 / 348 | 0 / 86 | 0 / 88 | 0 / 174 | 0 / 155 | 0 / 143 | 0 / 154 | 0 / 162 | 0 / 47 | 0 / 48 | 0 / 70 |
| other Total, other adverse events | 14 / 173 | 8 / 175 | 22 / 348 | 13 / 86 | 11 / 88 | 24 / 174 | 12 / 155 | 12 / 143 | 0 / 154 | 0 / 162 | 0 / 47 | 0 / 48 | 0 / 70 |
| serious Total, serious adverse events | 1 / 173 | 1 / 175 | 2 / 348 | 0 / 86 | 1 / 88 | 1 / 174 | 1 / 155 | 3 / 143 | 0 / 154 | 1 / 162 | 1 / 47 | 0 / 48 | 0 / 70 |
Outcome results
Primary
Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
A migraine day was defined as any calendar day in which participant experienced a qualified migraine headache (onset, continuation or recurrence of 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 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 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 on-DBT efficacy analysis period)/ (total number of eDiary efficacy data days through Month 3\[Weeks 1 to 12\] in the on-DBT efficacy analysis period).
Time frame: Observation Phase: 28 days prior to randomization and baseline; Entire DBT Phase: 12 weeks (Week 1 through 12)
Population: Migraine analysis set included participants in the DBT efficacy analysis set with \>= 14 days of e-diary efficacy data in both the observation phase and \>= 1 month (4-week interval) in the DBT phase. DBT efficacy analysis set: participants who were enrolled and randomized only once and took \>=1 dose of DB study drug (zavegepant or placebo). Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ statistical analysis plan (SAP).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | -7.0 Migraine Days per Month |
| Zavegepant 200 mg (DBT) | Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | -6.3 Migraine Days per Month |
| Placebo Pooled (DBT) | Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | -5.6 Migraine Days per Month |
97.5% CI: [-2.72, -0.12]
97.5% CI: [-2.07, 0.69]
Secondary
Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12
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.
Time frame: DBT Phase: Baseline (before dose on Day 1), Week 12
Population: DBT efficacy analysis set included participants in the full analysis set who were randomized only once and took \>= 1 dose of DB study drug (zavegepant or placebo). Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 | -26.8 Scores on a scale |
| Zavegepant 200 mg (DBT) | Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 | -27.1 Scores on a scale |
| Placebo Pooled (DBT) | Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 | -17.9 Scores on a scale |
97.5% CI: [-18.1, 0.19]
97.5% CI: [-18.95, 0.41]
Secondary
Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12
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.
Time frame: DBT Phase: Baseline (before dose on Day 1), Week 12
Population: DBT efficacy analysis set included participants in the full analysis set who were randomized only once and took \>= 1 dose of DB study drug (zavegepant or placebo). Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12 | 24.5 Scores on a scale |
| Zavegepant 200 mg (DBT) | Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12 | 20.6 Scores on a scale |
| Placebo Pooled (DBT) | Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12 | 20.5 Scores on a scale |
97.5% CI: [-1.5, 9.39]
97.5% CI: [-5.66, 5.86]
Secondary
Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase
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\[Week 1 to 4\]).
Time frame: Observation Phase: 28 days prior to randomization and baseline; DBT Phase: first 4 weeks (Week 1 through 4)
Population: Migraine analysis set analyzed. Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase | -5.7 Migraine Days per Month |
| Zavegepant 200 mg (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase | -5.1 Migraine Days per Month |
| Placebo Pooled (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase | -3.9 Migraine Days per Month |
97.5% CI: [-3.16, -0.42]
97.5% CI: [-2.53, 0.22]
Secondary
Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase
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\[Week 9 to 12\]).
Time frame: Observation Phase: 28 days prior to randomization and baseline; DBT Phase: last 4 weeks (Week 9 through 12)
Population: Migraine analysis set analyzed. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase | -7.8 Migraine Days per Month |
| Zavegepant 200 mg (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase | -7.2 Migraine Days per Month |
| Placebo Pooled (DBT) | Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase | -6.8 Migraine Days per Month |
97.5% CI: [-2.68, 0.58]
97.5% CI: [-2.1, 1.31]
Secondary
Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
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).
Time frame: Entire DBT Phase: 12 weeks (Week 1 through 12)
Population: Migraine analysis set included participants in the DBT efficacy analysis set with \>= 14 days of e-diary efficacy data in both the observation phase and \>= 1 month (4-week interval) in the DBT phase. DBT efficacy analysis set: participants who were enrolled and randomized only once and took \>=1 dose of DB study drug (zavegepant or placebo). Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 2.4 AM-specific Medication Days per Month |
| Zavegepant 200 mg (DBT) | Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 3.0 AM-specific Medication Days per Month |
| Placebo Pooled (DBT) | Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 3.2 AM-specific Medication Days per Month |
97.5% CI: [-1.59, 0.05]
97.5% CI: [-1.06, 0.74]
Secondary
Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase
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.
Time frame: DBT Phase: During 12 weeks of treatment
Population: DBT safety analysis set included the participants in the who were enrolled and who took \>=1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 2 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 5 Participants |
| Placebo Pooled (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 7 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 3 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 4 Participants |
| Placebo Pooled (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | 7 Participants |
Secondary
Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase
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.
Time frame: OLE: During 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase | 2 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase | 4 Participants |
Secondary
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase
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.
Time frame: DBT: During 12 weeks of treatment
Population: DBT safety analysis set included the participants in the who were enrolled and who took \>=1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date. Participants reported under Overall Number of Participants Analyzed contributed data but may not be evaluable for every row and Number Analyzed signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 7 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 5 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 4 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 7 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 6 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 3 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 3 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 13 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 5 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 12 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 2 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 3 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 5 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 3 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, fasting | 4 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Urinalysis | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Triglycerides | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol | 7 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Creatine Kinase | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Hemoglobin | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | Potassium, high | 3 Participants |
| Placebo Pooled (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase | LDL Cholesterol, not fasting | 1 Participants |
Secondary
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase
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.
Time frame: OLE: During 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date. Here, Number Analyzed signifies participants evaluable for the specified rows. Overall Number of Participants Analyzed contributed data to table but may not have evaluable data for every row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol, fasting | 4 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Creatine Kinase | 10 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol, not fasting | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Hemoglobin | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Potassium, high | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Glucose fasting, low | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | AST | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides, fasting | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides, not fasting | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol | 7 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Urinalysis | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Neutrophils | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Urinalysis | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Hemoglobin | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Neutrophils | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | AST | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Creatine Kinase | 7 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Glucose fasting, low | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol | 8 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol, fasting | 4 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | LDL Cholesterol, not fasting | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Potassium, high | 2 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides, not fasting | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase | Triglycerides, fasting | 1 Participants |
Secondary
Number of Participants With Hepatic-related AEs by Intensity: DBT Phase
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.
Time frame: DBT Phase: During 12 weeks of treatment
Population: DBT safety analysis set included the participants in the who were enrolled and who took \>=1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 0 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 1 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Moderate | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Severe | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs by Intensity: DBT Phase | Mild | 1 Participants |
Secondary
Number of Participants With Hepatic-related AEs by Intensity: OLE Phase
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.
Time frame: OLE: Over 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Moderate | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Mild | 1 Participants |
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Severe | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Mild | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Moderate | 2 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs by Intensity: OLE Phase | Severe | 1 Participants |
Secondary
Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase
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.
Time frame: DBT Phase: During 12 weeks of treatment
Population: DBT safety analysis set included the participants in the who were enrolled and who took \>=1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
| Placebo Pooled (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase | 0 Participants |
Secondary
Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: OLE Phase
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.
Time frame: OLE: Over 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: OLE Phase | 0 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: OLE Phase | 1 Participants |
Secondary
Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase
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.
Time frame: DBT Phase: During 12 weeks of treatment
Population: DBT safety analysis set included the participants who were enrolled and took \>= 1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 20 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 25 Participants |
| Placebo Pooled (DBT) | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 45 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 13 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 9 Participants |
| Placebo Pooled (DBT) | Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase | 22 Participants |
Secondary
Number of Participants With Moderate or Severe AEs: OLE Phase
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.
Time frame: OLE: During 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Moderate or Severe AEs: OLE Phase | 29 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Moderate or Severe AEs: OLE Phase | 37 Participants |
Secondary
Number of Participants With SAEs: OLE Phase
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.
Time frame: OLE: During 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With SAEs: OLE Phase | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With SAEs: OLE Phase | 3 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs): DBT Phase
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.
Time frame: DBT Phase: During 12 weeks of treatment
Population: DBT safety analysis set included the participants who were enrolled and took \>= 1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 1 Participants |
| Zavegepant 200 mg (DBT) | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 2 Participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 0 Participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 1 Participants |
| Placebo Pooled (DBT) | Number of Participants With Serious Adverse Events (SAEs): DBT Phase | 1 Participants |
Secondary
Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 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 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).
Time frame: Entire DBT Phase: 12 weeks (Week 1 through 12)
Population: Migraine analysis set included participants in the DBT efficacy analysis set with \>= 14 days of e-diary efficacy data in both the observation phase and \>= 1 month (4-week interval) in the DBT phase. DBT efficacy analysis set: participants who were enrolled and randomized only once and took \>=1 dose of DB study drug (zavegepant or placebo). Results were summarized by treatment group and the 2 matching placebo groups were pooled as pre-specified in protocol/ SAP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 56.1 Percentage of participants |
| Zavegepant 200 mg (DBT) | Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 46.6 Percentage of participants |
| Placebo Pooled (DBT) | Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12) | 40.0 Percentage of participants |
97.5% CI: [4.4, 28.8]
97.5% CI: [-5.6, 18.9]
Secondary
Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase
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.
Time frame: DBT: Over 12 weeks of treatment
Population: DBT safety analysis set included the participants in the who were enrolled and who took \>=1 dose of DB study drug (zavegepant or placebo), i.e., non-missing study drug start date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
| Zavegepant 200 mg (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
| Placebo Pooled (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
| Placebo (DBT) Matched to Zavegepant 100 mg | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
| Placebo (DBT) Matched to Zavegepant 200 mg | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
| Placebo Pooled (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase | 0 Percentage of participants |
Secondary
Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: OLE Phase
Elevations of AST or ALT \> 3 \* ULN concurrent with TBL \> 2 \*ULN were defined as elevations on the same collection date.
Time frame: OLE: Over 52 weeks of treatment
Population: OL safety analysis set included the participants who took \>= 1 dose of OL zavegepant, i.e., nonmissing OL zavegepant start date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 100 mg (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: OLE Phase | 0 Percentage of participants |
| Zavegepant 200 mg (DBT) | Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: OLE Phase | 0 Percentage of participants |