This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine (NCT04408794), a na phase 2, phase 3 study. The primary outcome is Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04408794 |
| Phase | Phase 2, Phase 3 |
| Condition | Acute Migraine |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 974 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Participants with acute migraine who enrolled in the study and took study drug were included in the safety analysis set. The registry reports enrollment of 974 participants and defines the safety set as enrolled participants with a non-missing study-drug start date and time. The posted safety counts use a group of 603 participants at risk. The registry record does not provide further demographic or clinical detail about this group in the information reported.
Intervention
The intervention was zavegepant, identified in the study record as BHV-3500. The regimen was 10 mg intranasally, up to 8 times per month, for up to 1 year. The study evaluated long-term safety during acute treatment of migraine; the record does not describe a daily preventive regimen.
Comparator
There was no comparison group. The design is listed as a single-group study with no masking, and allocation is recorded as not applicable. Consequently, the results describe events among participants receiving zavegepant but do not provide a randomized or like-for-like comparison against placebo or another treatment.
Primary question
The primary question was how many participants experienced adverse events, serious adverse events, or adverse events leading to discontinuation from study-drug dosing through the end of the study, up to 52 weeks. An adverse event was defined as a new untoward medical occurrence or worsening of a pre-existing condition after administration of the investigational product; the definition does not require the event to be caused by treatment. Serious adverse events were defined using specified seriousness criteria, including death, life-threatening events, hospitalization, persistent or significant disability, congenital anomaly, and other medically important events.
3. Trial Design
The registry identifies this as a Phase 2/3, open-label, long-term safety trial of intranasal BHV-3500, now referred to as zavegepant, for acute migraine. The study is listed as completed. Its stated purpose was to evaluate long-term safety during acute treatment. The record gives a start date of 2020-06-29 and a primary completion date of 2021-12-09.
The study used a single-group design. Allocation is not applicable, and masking was absent. Participants received zavegepant 10 mg intranasally, up to 8 times per month, for up to 1 year. No concurrent control arm is described. This design can characterize events recorded while participants were exposed to the study drug, but it cannot establish how those events compare with events under a different treatment or with no study treatment.
Enrollment was 974. The primary safety population was defined as enrolled participants who took study drug, indicated by a non-missing study-drug start date and time. For the posted adverse-event results, the group at risk is listed as 603 participants. These figures refer to different registry descriptions: enrollment and the safety analysis population should not be treated as interchangeable. The record does not provide further information in these results about the reasons participants were not included in the safety population or their follow-up.
The primary outcome concerns the number of participants with adverse events, serious adverse events, and adverse events leading to discontinuation from dosing through the end of the study, up to 52 weeks. The registry lists two outcome measures, but the additional measure and its results are not reported in the registry record. A detailed statistical analysis plan, sample-size justification, or account of interim analyses is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 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.
Overall Study
| Stage | Zavegepant 10 mg |
|---|---|
| STARTED | 608 |
| Treated/Safety Analysis Set | 603 |
| COMPLETED | 341 |
| NOT COMPLETED | 267 |
Reasons for not completing this period:
| Reason | Zavegepant 10 mg |
|---|---|
| Adverse Event | 43 |
| Infrequent study drug usage | 43 |
| Lack of Efficacy | 61 |
| Lost to Follow-up | 33 |
| Non-compliance | 6 |
| Physician Decision | 1 |
| Pregnancy | 6 |
| Protocol Deviation | 9 |
| Sheehan-STS Result | 1 |
| Withdrawal by Subject | 57 |
| Terminated study prematurely due to COVID-19 - Adverse Event | 2 |
| Never Treated Migraine | 5 |
Analysis population for the primary outcome, as defined in the registry: Safety analysis set included participants in the enrolled analysis set who took the study drug, that is, non-missing study drug start date/time.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
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.
| Characteristic | Unit | Zavegepant 10 mg |
|---|---|---|
| Participants analysed | 603 | |
| Age, Continuous | years | 42.1 (SD 12.46) |
| Sex: Female, Male: Female | Participants | 517 |
| Sex: Female, Male: Male | Participants | 86 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 71 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 532 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 |
| Race (NIH/OMB): Asian | Participants | 23 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 2 |
| Race (NIH/OMB): Black or African American | Participants | 70 |
| Race (NIH/OMB): White | Participants | 502 |
| Race (NIH/OMB): More than one race | Participants | 4 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation, measured over From study drug dosing up to the end of the study (up to 52 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a safety endpoint: the number of participants who experienced adverse events, serious adverse events, or adverse events leading to discontinuation during the period from study-drug dosing through the end of the study, up to 52 weeks. The record defines an adverse event broadly as a new untoward medical occurrence or worsening of a pre-existing medical condition after administration of the investigational product. An event need not be judged to have been caused by the treatment to meet that definition.
Seriousness is based on the nature or consequences of an event, not simply on how often it occurs. The registry definition includes death, life-threatening events, inpatient hospitalization or prolonged hospitalization, persistent or significant disability, congenital anomaly, and other medically important events that may require intervention to prevent a serious outcome. Thus, serious adverse events are a subset defined by seriousness criteria, while the broader adverse-event measure captures occurrences that may be less serious.
Counting participants with events is useful in a long-term safety study because it gives a direct descriptive account of how many people in the analyzed group had recorded events. It does not by itself describe event severity beyond the separate serious-event classification, duration, recurrence, or causal relationship to treatment. The registry record does not report those details for the overall adverse-event count. Nor does a participant count indicate the rate of events per unit of exposure. These results should therefore be read as descriptive safety findings within the recorded follow-up, rather than as a comparative estimate of treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
Among the 603 participants listed as at risk in the zavegepant group, 7 participants had a serious adverse event, and 336 participants had other adverse events. The registry also reports 0 deaths. These are participant counts, not a randomized comparison between treatment groups. The results describe events recorded during study participation and do not show whether zavegepant caused an event.
The listed serious adverse-event terms include appendicitis, herpes zoster meningoencephalitis, pneumonia, bile duct stenosis, concussion, and fall. Each term is reported as 0.2%. The record does not state in this information whether a term could include more than one event per participant or give additional detail about each event, its timing, outcome, or relationship to treatment. The listed terms should not be interpreted as a complete clinical narrative of the serious events.
Because there is only one group, these counts cannot answer whether the observed events were more or less common than they would have been without zavegepant or with another treatment. Events can occur during a study regardless of whether study treatment is responsible. Without a concurrent comparator and an appropriate comparative analysis, the registry results support description, not attribution. The open-label design also means participants and investigators were not masked to treatment, which can influence reporting or assessment of some outcomes.
The follow-up period is described as extending from dosing to the end of the study, up to 52 weeks, while the regimen allowed use up to 8 times per month for up to 1 year. The registry does not report participant-level exposure duration, actual dosing frequency, or event timing in the record. As a result, the counts do not account for how long each participant was observed or how often each participant used the drug. A raw count cannot be interpreted as an exposure-adjusted rate.
The zero deaths figure means that no deaths are reported in the posted group results; it does not establish that all other serious risks are absent or that rare events could not occur. Similarly, the overall counts do not describe the clinical importance of each non-serious event. The registry record does not report inferential estimates such as confidence intervals or a comparative effect estimate for these safety counts. Their precision cannot therefore be judged from the counts alone. The interpretation is limited to the reported population, event definitions, and follow-up period.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is expressed as the number of participants with an event. This is a count of people meeting the outcome definition, rather than a count of every episode or a measure of events per unit of time. A participant who experiences more than one event can contribute to more than one event category in safety reporting; counts across categories therefore should not automatically be added. The posted information reports 7 participants with serious adverse events and 336 participants with other adverse events, with 603 listed at risk. It also reports 0 deaths. These values describe the recorded group and are not treatment-versus-control estimates.
In general, a proportion can be calculated by dividing the number of participants with an event by the number at risk. No additional proportions should be inferred unless they are explicitly reported, because the appropriate denominator and handling of follow-up must be clear. For studies with different observation times, a simple proportion can obscure unequal exposure. An exposure-adjusted rate instead relates events to accumulated time at risk, but participant-level time and such a rate are not reported in the registry record.
Why distinguish serious from other adverse events?
In general, seriousness classifies an event according to its consequences or medical importance, rather than its frequency or intensity alone. The registry definition includes events such as death, life-threatening events, hospitalization, persistent or significant disability, congenital anomaly, and other important medical events. The broader adverse-event definition includes new or worsening medical occurrences without requiring a causal relationship to study drug. Therefore, the serious-event count and the count for other adverse events answer related but different descriptive questions.
The distinction does not prove that an event was caused by the study drug. Causality is a separate assessment. The posted descriptions define adverse events and serious adverse events but do not report event-by-event causality assessments, severity grades, timing, duration, or outcomes. The reported counts should not be read as causal effects.
What can a single-group design estimate?
In general, a single-group safety study can describe events observed among participants who received the study intervention. It cannot by itself estimate the difference in risk between treatment and a comparator. A comparison would require a suitable control group and an analysis designed to account for differences between groups. This study is listed as single-group, open-label, and without a randomized comparison, so its event counts are descriptive rather than comparative.
Randomization can help balance known and unknown factors between groups, while masking can reduce some influences on reporting and assessment. Neither is present as a treatment comparison in this record. This does not make the descriptive counts uninformative; it defines the claims they can support. They characterize recorded safety experience under the study regimen, but they do not isolate the contribution of treatment from background illness, other exposures, or other causes.
How does follow-up affect interpretation?
In general, participants may have different amounts of time under observation or different exposure to a treatment. A participant-level event count does not represent these differences. Time-to-event or exposure-adjusted methods can incorporate follow-up time, but those approaches require data and analyses that are not reported in the registry record. Here, the outcome timeframe extends from dosing through study end, up to 52 weeks, and the regimen permits use up to 8 times per month for up to 1 year. The record does not report actual use or follow-up duration for each participant.
Confidence intervals are general statistical tools for expressing uncertainty around an estimated quantity. A wider interval usually indicates less precision, while a narrower interval indicates greater precision under the assumptions of the method. No confidence interval for the posted event counts is reported in the registry record. Without one, and without comparative estimates, the precision of differences or risks cannot be assessed from this information.
What analyses are reported?
The registry record reports the event counts and lists 0 analyses. It does not report a statistical analysis plan, adjusted analyses, hypothesis tests, or an account of interim analyses. These omissions mean there is no reported inferential framework to evaluate alongside the descriptive counts. A lack of a reported analysis should not be mistaken for evidence that an analysis found no difference; there is no randomized comparison in the design to assess in the first place.
In general, multiplicity arises when several outcomes or comparisons are tested, increasing the chance of a chance-positive finding if each test is interpreted separately. A plan for managing multiple tests is useful when confirmatory inference is intended. The information in the registry record does not state how multiplicity was handled. It also does not provide a sample-size justification or explain how the enrolled number was chosen. Those design details cannot be inferred from the observed event counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and reports 0 analyses. The primary safety outcome is described, but the other outcome measure and its result are not reported in the registry record. A prespecified analysis plan, including any hierarchy of outcomes or approach to multiple testing, is not reported in the registry record. Consequently, the record does not establish whether multiplicity was relevant to the intended analyses or how it would have been addressed. No confirmatory hypothesis tests or adjusted comparisons are reported.
Missing-data methods are also not reported in the registry record. The safety population is defined as enrolled participants who took study drug, identified by a non-missing start date and time. This definition indicates who was eligible for the safety analysis set, but it does not explain how missing event information, incomplete follow-up, or withdrawal was handled. The reasons that enrollment and the safety analysis population differ are not reported in the registry record. No imputation method, censoring approach, or sensitivity analysis is described.
The record's outcome timeframe is from dosing to study end, up to 52 weeks. The available counts alone do not show whether all participants had the same observation period or the same amount of drug exposure. Participant-level follow-up and dose use are not reported in the registry record, limiting assessment of how incomplete observation might affect the event counts.
The primary population is a safety analysis set rather than a randomized comparison population. No randomized allocation is described, and there is no control group. The registry record does not report a separate population for an efficacy analysis, a per-protocol analysis, or an intention-to-treat comparison. The results should therefore be understood in relation to the defined safety set and not generalized to an unreported analysis population.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Zavegepant 10 mg | 7 | 603 | 1.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Zavegepant 10 mg | 0 of 603 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Zavegepant 10 mg | 336 of 603 |
Most frequent serious adverse event terms
| Event term | Organ system | Zavegepant 10 mg |
|---|---|---|
| Appendicitis | Infections and infestations | 1 of 603 |
| Herpes zoster meningoencephalitis | Infections and infestations | 1 of 603 |
| Pneumonia | Infections and infestations | 1 of 603 |
| Bile duct stenosis | Hepatobiliary disorders | 1 of 603 |
| Concussion | Injury, poisoning and procedural complications | 1 of 603 |
| Fall | Injury, poisoning and procedural complications | 1 of 603 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 603 |
| Multiple sclerosis | Nervous system disorders | 1 of 603 |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | 1 of 603 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Zavegepant 10 mg |
|---|---|---|
| Dysgeusia | Nervous system disorders | 236 of 603 |
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | 62 of 603 |
| COVID-19 | Infections and infestations | 45 of 603 |
| Nausea | Gastrointestinal disorders | 37 of 603 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 33 of 603 |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | 33 of 603 |
| Back pain | Musculoskeletal and connective tissue disorders | 33 of 603 |
Serious events with the highest arm-level rate: appendicitis (0.2%), herpes zoster meningoencephalitis (0.2%), pneumonia (0.2%), bile duct stenosis (0.2%), concussion (0.2%).
The serious adverse-event results report 7 participants with at least one serious adverse event among 603 listed at risk in the zavegepant group. The registry reports 0 deaths. Seriousness follows the registry's criteria, which include death, life-threatening events, hospitalization, persistent or significant disability, congenital anomaly, and other important medical events. A serious adverse event is not automatically an event caused by the study drug; the adverse-event definition explicitly does not require a causal relationship.
The registry lists appendicitis, herpes zoster meningoencephalitis, pneumonia, bile duct stenosis, concussion, and fall as serious-event terms, each reported as 0.2%. These percentages are reproduced as recorded. The record does not give further details about timing, clinical course, causality, or whether the listed terms account for all serious events. They should not be interpreted as evidence that the drug caused those conditions.
The count of serious adverse events and the count of other adverse events are different safety summaries. They are not a comparative risk estimate and should not be combined into a new total. In general, a participant may be associated with multiple event categories, and a participant count does not convey event recurrence or exposure duration. The registry record does not report exposure-adjusted rates or confidence intervals, so the results are best read as descriptive counts within the reported safety group.
12. What the Result Does, and Does Not, Mean
The posted results show that adverse events and serious adverse events were recorded among participants in a long-term, open-label study of intranasal zavegepant. Specifically, the registry reports 7 participants with serious adverse events, 336 participants with other adverse events, and 0 deaths among 603 participants listed at risk. The serious-event terms and their reported percentages provide additional descriptive detail, but the record does not report event-level context or causal assessments.
These observations matter as a record of safety experience under the study regimen: 10 mg intranasally, up to 8 times per month, for up to 1 year. The primary outcome timeframe extended from dosing until study end, up to 52 weeks. However, the record does not provide individual exposure duration, actual dosing frequency, or event timing. Thus the counts do not indicate an event rate per participant-time or account for possible variation in follow-up.
The results do not establish that zavegepant caused the reported events. The adverse-event definition includes occurrences that do not necessarily have a causal relationship to treatment. The single-group design also has no control arm, so it cannot show whether event occurrence differed from what would have been observed under another treatment or without study drug. Open-label conduct means treatment was not masked, and no randomized comparison is reported.
The findings also do not establish that a risk is absent. A count of 0 deaths is a report about the observed group, not proof that deaths or other rare events could never occur. Nor do the counts establish the frequency or severity of every type of event. The registry record does not report confidence intervals or comparative statistical analyses that would quantify precision or differences.
In short, this is a descriptive account of recorded safety outcomes for the defined safety population and follow-up. It should not be interpreted as proof of benefit, proof of harm, or a comparison with an alternative. The registry record does not report a sample-size justification, detailed missing-data methods, or an analysis plan that would support broader inferential claims.
13. Why This Trial Matters Statistically
Long-term safety studies address a different statistical question from trials designed primarily to compare efficacy. For a treatment used intermittently over an extended period, documenting adverse events during ongoing use is important to describe the observed safety experience and identify events that warrant further evaluation. This study's primary endpoint captures participants with adverse events, serious adverse events, and events leading to discontinuation over a timeframe of up to 52 weeks.
The design also illustrates a key distinction in interpretation: descriptive surveillance and comparative inference are not the same. A single-group study can record the frequency and types of events observed during treatment, but without a control group it cannot estimate how those outcomes differ from a comparator. The open-label design and absence of randomized allocation further define the limits of causal interpretation. Statistical analysis cannot recover a treatment comparison that the design does not include.
The registry's separation of serious adverse events from other adverse events is useful because these categories have distinct definitions and clinical implications. The serious-event criteria include hospitalization, life-threatening events, and other medically important outcomes, while the broader adverse-event definition includes new or worsening medical occurrences without requiring causation. Reading both types of counts provides more context than treating all events as interchangeable.
The record also highlights why participant counts need context. The population at risk is reported, but individual follow-up and exposure are not. In general, counts alone do not account for differing time under observation, repeat events, or dosing patterns. Reporting exposure-adjusted estimates and uncertainty could help characterize those dimensions, but such results are not reported in the registry record.
Statistically, the value of this study is therefore its descriptive contribution: it documents a safety population, regimen, timeframe, and recorded event counts. Its results can inform the questions asked in later analyses, while remaining limited to the design and outcomes reported. They do not constitute a randomized estimate of comparative safety.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation is the single-group design. There is no control group, and allocation is listed as not applicable. The study is open-label, with no masking. As a result, the event counts cannot distinguish treatment-associated risk from background events or other influences, and reporting or assessment may be affected by knowledge of treatment.
The registry reports 974 enrolled participants but lists 603 at risk for the posted safety outcomes. The safety analysis set is defined by enrollment and a non-missing study-drug start date and time. The reasons for the difference between enrollment and the reported group at risk are not reported in the registry record. The record also does not explain whether participants had complete follow-up, how withdrawals were handled, or how missing event information was addressed.
Although the timeframe extends to the end of the study, up to 52 weeks, individual follow-up duration, actual dosing frequency, and cumulative exposure are not reported in the registry record. Therefore, the participant counts cannot account for differences in observation time or be interpreted as exposure-adjusted rates. Recurrence and timing of events are also not described in the posted information.
The registry lists serious-event terms and percentages but does not report their clinical course, outcome, causal assessment, or detailed event-level counts. It reports no confidence intervals or inferential analyses for these safety results. The statistical analysis plan, approach to multiplicity, sample-size justification, and interim-analysis procedures are not reported in the registry record. The information also does not describe the additional outcome measure among the two listed measures. These gaps limit assessment of precision, missingness, and the full prespecified analysis framework.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine — NCT04408794.
- Registry record last updated 2023-05-18; status last verified 2023-05.
- Results first posted 2023-03-16.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT04408794 is a completed Phase 2/3, open-label, single-group safety study of intranasal zavegepant, identified as BHV-3500 in the study title, for acute migraine. The regimen was 10 mg up to 8 times per month for up to 1 year. Enrollment was 974, and the safety population was defined as enrolled participants who took study drug. The posted safety group lists 603 participants at risk.
The primary outcome measured participants with adverse events, serious adverse events, and adverse events leading to discontinuation from dosing through study end, up to 52 weeks. The registry reports 7 participants with serious adverse events, 336 participants with other adverse events, and 0 deaths. Six serious-event terms are each reported as 0.2%. The design has no randomized comparator, and the reported counts are descriptive, not estimates of comparative treatment effects. Statistical analysis details, missing-data methods, and sample-size justification are not reported in the registry record.