Acute Migraine
Conditions
Keywords
migraine, headache, intranasal
Brief summary
The purpose of this study is to evaluate the long-term safety of BHV-3500/vazegepant intranasal in the acute treatment of migraine. \* BHV-3500, formerly vazegepant, is now referred to as zavegepant (za ve' je pant). The World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee revised the name to zavegepant which was accepted by the United States Adopted Names (USAN ) Council for use in the U.S. and is pending formal adoption by the INN for international use.
Interventions
10 mg IN up to 8 times per month, up to 1 year
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 2-8 moderate to severe migraines/month within the last 3 months * Migraine attacks present for more than 1 year with age of onset of migraines prior to 50 years of age * Migraine attacks, on average, lasting about 4-72 hours if untreated * Less than 15 days with headaches (migraine or non-migraine) per month in each of the 3 months prior to the screening visit * Ability to distinguish migraine attacks from tension/cluster headaches * Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria
Exclusion criteria
* History of human immunodeficiency virus disease * History of basilar or hemiplegic migraine * Current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder * History of nasal surgery in the 6 months preceding the screening visit * History of gallstones or cholecystectomy * History of gastric, or small intestinal surgery (including gastric bypass, gastric banding, gastric sleeve, gastric balloon, etcetera), or other disease or condition (for example, chronic pancreatitis, ulcerative colitis, etcetera) that causes malabsorption. * Body mass index ≥ 33 * Hemoglobin A1c ≥6.5%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation | From study drug dosing up to the end of the study (up to 52 weeks) | An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product that does not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria at any dose: 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 who received study drug; 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 to prevent one of the other serious outcomes. |
| Number Of Participants With Clinically Significant Laboratory Abnormalities | From study drug dosing up to the end of the study (up to 52 weeks) | Clinically significant laboratory abnormalities were defined as Grades 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome. Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, low-density lipoprotein (LDL)-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in to be included for a given parameter. Laboratory results were presented in US units. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 63 sites in the United States.
Pre-assignment details
A total of 974 participants were enrolled for this open-label study, of which 900 participants entered the observational phase (OP) and 608 participants entered the long-term treatment (LTT) phase, of whom 603 participants received treatment with zavegepant. A total of 286 participants failed to enter the LTT phase after the OP due to failure to meet inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Zavegepant 10 mg Participants self-administered zavegepant 10 mg nasal spray, taken up to 8 times per month (28 days), for up to 52 weeks. The dose was self-administered using an Aptar UDS liquid spray device. | 603 |
| Total | 603 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 43 |
| Overall Study | Infrequent study drug usage | 43 |
| Overall Study | Lack of Efficacy | 61 |
| Overall Study | Lost to Follow-up | 33 |
| Overall Study | Never Treated Migraine | 5 |
| Overall Study | Non-compliance | 6 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Pregnancy | 6 |
| Overall Study | Protocol Deviation | 9 |
| Overall Study | Sheehan-STS Result | 1 |
| Overall Study | Terminated study prematurely due to COVID-19 - Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 57 |
Baseline characteristics
| Characteristic | Zavegepant 10 mg |
|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 532 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 70 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 502 Participants |
| Sex: Female, Male Female | 517 Participants |
| Sex: Female, Male Male | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 603 |
| other Total, other adverse events | 336 / 603 |
| serious Total, serious adverse events | 7 / 603 |
Outcome results
Primary
Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product that does not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria at any dose: 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 who received study drug; 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 to prevent one of the other serious outcomes.
Time frame: From study drug dosing up to the end of the study (up to 52 weeks)
Population: Safety analysis set included participants in the enrolled analysis set who took the study drug, that is, non-missing study drug start date/time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zavegepant 10 mg | Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation | AEs | 460 Participants |
| Zavegepant 10 mg | Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation | SAEs | 7 Participants |
| Zavegepant 10 mg | Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation | AEs leading to discontinuation | 41 Participants |
Primary
Number Of Participants With Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities were defined as Grades 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome. Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, low-density lipoprotein (LDL)-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in to be included for a given parameter. Laboratory results were presented in US units.
Time frame: From study drug dosing up to the end of the study (up to 52 weeks)
Population: Safety analysis set included participants in the enrolled analysis set who took the study drug, that is, non-missing study drug start date/time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Alanine Aminotransferase | 3 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Uric Acid | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Eosinophils | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Hemoglobin | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Lymphocytes, low | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Albumin | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Aspartate Aminotransferase | 5 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Alkaline Phosphatase | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Bicarbonate | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Biliburin | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Calcium, low | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Calcium, high | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Cholesterol | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Creatine Kinase (All Methods) | 13 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Creatine Kinase | 13 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Creatinine | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Glomerular Filtration Rate, Estimated | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | LDL-cholesterol | 21 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | LDL-cholesterol, fasting | 6 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | LDL-cholesterol, not fasting | 15 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Lactate Dehydrogenase | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Potassium, low | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Potassium, high | 1 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Sodium, low | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Sodium, high | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides | 1 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides, fasting | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Triglycerides, not fasting | 1 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Lymphocytes, high | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Neutrophils | 2 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Platelets | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | White Blood Cells | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Qualitative Glucose | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Qualitative Protein | 0 Participants |
| Zavegepant 10 mg | Number Of Participants With Clinically Significant Laboratory Abnormalities | Urine Erythrocytes | 0 Participants |