Trial Outcomes & Findings for Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine (NCT NCT04408794)

Last Updated: 2023-05-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

974 participants

Primary outcome timeframe

From study drug dosing up to the end of the study (up to 52 weeks)

Results posted on

2023-05-18

Participant Flow

The study was conducted at 63 sites in the United States.

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.

Participant milestones

Participant milestones
Measure	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 Unidose System (UDS) liquid spray device.
Overall Study STARTED	608
Overall Study Treated/Safety Analysis Set	603
Overall Study COMPLETED	341
Overall Study NOT COMPLETED	267

Reasons for withdrawal

Reasons for withdrawal
Measure	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 Unidose System (UDS) liquid spray device.
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 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 Withdrawal by Subject	57
Overall Study Terminated study prematurely due to COVID-19 - Adverse Event	2
Overall Study Never Treated Migraine	5

Baseline Characteristics

Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zavegepant 10 mg n=603 Participants 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.
Age, Continuous	42.1 years STANDARD_DEVIATION 12.46 • n=5 Participants
Sex: Female, Male Female	517 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	71 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	532 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	23 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	70 Participants n=5 Participants
Race (NIH/OMB) White	502 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Zavegepant 10 mg n=603 Participants 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.
Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation AEs	460 Participants
Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation SAEs	7 Participants
Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation AEs leading to discontinuation	41 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Zavegepant 10 mg n=579 Participants 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.
Number Of Participants With Clinically Significant Laboratory Abnormalities Aspartate Aminotransferase	5 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Albumin	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Alkaline Phosphatase	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Bicarbonate	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Biliburin	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Calcium, low	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Calcium, high	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Cholesterol	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Creatine Kinase (All Methods)	13 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Creatine Kinase	13 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Creatinine	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Glomerular Filtration Rate, Estimated	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities LDL-cholesterol	21 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities LDL-cholesterol, fasting	6 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities LDL-cholesterol, not fasting	15 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Lactate Dehydrogenase	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Potassium, low	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Potassium, high	1 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Sodium, low	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Sodium, high	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Triglycerides	1 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Triglycerides, fasting	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Triglycerides, not fasting	1 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Uric Acid	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Eosinophils	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Hemoglobin	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Lymphocytes, low	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Lymphocytes, high	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Neutrophils	2 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Platelets	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities White Blood Cells	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Qualitative Glucose	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Qualitative Protein	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Urine Erythrocytes	0 Participants
Number Of Participants With Clinically Significant Laboratory Abnormalities Alanine Aminotransferase	3 Participants

Adverse Events

Zavegepant 10 mg

Serious events: 7 serious events

Other events: 336 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zavegepant 10 mg n=603 participants at risk 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.
Infections and infestations Appendicitis	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Infections and infestations Herpes zoster meningoencephalitis	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Infections and infestations Pneumonia	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Hepatobiliary disorders Bile duct stenosis	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Injury, poisoning and procedural complications Concussion	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Injury, poisoning and procedural complications Fall	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Musculoskeletal and connective tissue disorders Back pain	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Nervous system disorders Multiple sclerosis	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Respiratory, thoracic and mediastinal disorders Pleurisy	0.17% 1/603 • From study drug dosing up to the end of the study (up to 52 weeks)

Other adverse events

Other adverse events
Measure	Zavegepant 10 mg n=603 participants at risk 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.
Nervous system disorders Dysgeusia	39.1% 236/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Respiratory, thoracic and mediastinal disorders Nasal discomfort	10.3% 62/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.5% 33/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Respiratory, thoracic and mediastinal disorders Throat irritation	5.5% 33/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Infections and infestations COVID-19	7.5% 45/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Gastrointestinal disorders Nausea	6.1% 37/603 • From study drug dosing up to the end of the study (up to 52 weeks)
Musculoskeletal and connective tissue disorders Back pain	5.5% 33/603 • From study drug dosing up to the end of the study (up to 52 weeks)

Additional Information

Chief Medical Officer

Biohaven Pharmaceuticals, Inc.

Phone: 203-404-0410

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60