Safety and Tolerability of POD-DHE (INP104) in Migraine (STOP 301): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of POD-DHE (INP104) in Migraine (STOP 301) (NCT03557333), a na phase 3 study. The primary outcome is Number of Participants With Serious Adverse Events (SAEs).

2. Clinical Question

STOP 301 therefore addresses a descriptive safety question: what serious adverse events were recorded during treatment and follow-up in this open-label study? The outcome is a participant count, not a measure of migraine symptom change or treatment benefit. It also does not, by itself, establish whether an event was caused by INP104. The endpoint explicitly includes serious adverse events regardless of their relationship to study drug.

The registry reports 5 participants with serious adverse events among 354 at risk in the 24-Week Treatment Group, and 3 among 73 at risk in the 52-Week Treatment Group. These figures describe the two recorded treatment-duration groups. Because the extension involved a subset and the study did not randomize participants between groups, the counts should not be interpreted as a controlled comparison of treatment duration.

3. Trial Design

STOP 301 is listed as a completed Phase 3, open-label, single-group study of INP104 in participants with migraine headache. The registry reports enrollment of 360. The trial began on 2018-07-13 and reached primary completion on 2020-03-17. Its official title describes chronic intermittent use of intranasal dihydroergotamine mesylate delivered with the I123 Precision Olfactory Delivery device.

The brief summary describes a 4-week screening period followed by a 24-week treatment period for all participants. A subset of at least 60 and up to 80 participants was to continue in a 28-week extension, reaching 52 weeks of treatment in total. A 2-week post-treatment follow-up period was also described. The arm description likewise identifies the extension as a continuation for a subset of participants.

The registry presents outcomes by the 24-Week Treatment Group and the 52-Week Treatment Group. These labels reflect treatment duration, not randomized treatment assignments. Allocation is recorded as not applicable, masking as none, and the design model as single group. The two groups therefore should not be treated as independent randomized arms or as intervention and control groups. The longer-duration group is described as a subset, and exposure and observation periods differ.

The primary outcome timeframe ends at Week 26 for the 24-Week Treatment Group and at Week 54 for the 52-Week Treatment Group. The registry lists four outcome measures and zero analyses. Detailed protocol procedures, the rationale for the planned enrollment, and a statistical analysis plan are not reported in the registry record. The posted results can be read as descriptive safety reporting, but the record does not establish a comparative design for evaluating differences between the duration groups.

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: 360 participants were enrolled and were dispensed INP104. Only those participants who dosed at least once with INP104 were included in the 24-Week Treatment Group, which was 354.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Adverse Events (SAEs), measured over From study enrollment up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group).

The primary endpoint is the number of participants with serious adverse events, whether or not those events were related to study drug. It is a count of participants, rather than a count of every event experienced by those participants. The registry gives the observation window as enrollment through Week 26 for the 24-Week Treatment Group and through Week 54 for the 52-Week Treatment Group.

Serious adverse events are an important safety outcome in clinical research because they capture events meeting seriousness criteria, rather than only routine symptoms or minor complaints. A participant count offers a direct description of how many participants in each recorded group had at least one such event during the stated timeframe. It does not describe the number of separate events per participant, their duration, or their severity beyond their classification as serious.

The endpoint includes events whether or not they were attributed to study drug. That broad definition can help describe the serious events observed during the study, but it does not answer whether treatment caused them. Attribution, clinical circumstances, and comparison with an appropriate control group would be needed to address causality. The registry record does not report a causal estimate for this endpoint.

Because the follow-up windows differ by group, the counts are not observations over identical periods. The endpoint is therefore most appropriately read as a safety count within each group’s specified follow-up, not as a direct estimate of the relative safety of shorter and longer treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: whether a participant was reported to have a serious adverse event during the stated observation period. The posted result gives the number of participants with an event and the number at risk in each treatment-duration group. These counts are useful for describing the study record, but they do not contain the participant-level timing or clinical detail needed for more elaborate analyses.

What does a participant count represent?

A participant count differs from an event count. If one participant has multiple serious adverse events, a count of participants with an event still represents that participant once for the outcome as defined. The registry labels the measure as a count of participants, but it does not report the number of separate serious events or how many participants experienced repeated events. Those details should not be inferred from the participant totals.

The denominator described as at risk identifies the group size used alongside the participant count in the registry’s safety reporting. Reading the count together with that denominator conveys how many participants in that recorded group had an event. It does not, by itself, account for differences in time under observation, participant characteristics, or the process by which participants entered the longer extension.

Why do observation windows matter?

The primary timeframe runs through Week 26 for the 24-Week Treatment Group and through Week 54 for the 52-Week Treatment Group. In general, a longer observation window can create more opportunity to detect an event. When groups have different follow-up durations, a simple comparison of participant counts does not isolate an effect of duration. Time-to-event methods can sometimes address differing follow-up, but they require suitable time-to-event data and a defined analysis. Such an analysis is not reported in the registry record.

The extension group is described as a subset, not as a separate randomized control group. In general, participants who continue into an extension may differ from those who do not, and that selection can make group comparisons difficult to interpret. The registry record does not report enough information to assess selection into the extension or adjust for potential differences.

What can confidence intervals add?

In general, a confidence interval expresses uncertainty around an estimate under a stated statistical method and its assumptions. It helps distinguish a relatively precise estimate from one compatible with a broad range of underlying values. The registry record does not report a confidence interval for the primary count or a comparative estimate between duration groups. No precision interval should therefore be inferred from the posted counts alone.

A count can be described without a formal hypothesis test, which is appropriate for a descriptive safety summary. A p-value would address a specified statistical comparison under a model; it would not establish causation or make a nonrandomized comparison equivalent to a randomized one. No p-value or primary-outcome analysis is listed in the registry record. The record’s listed outcome measure and posted counts should consequently be treated as descriptive rather than as a test of whether the groups differ.

Why is over-dispersion relevant in some analyses?

In general, over-dispersion occurs when observed variation in count data exceeds what a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not allow for that extra variation. The primary result is reported as participants with an event, not as a recurrent-event rate, and the registry does not report a model or an over-dispersion assessment. There is no basis in the record to claim that an over-dispersion adjustment was used or needed for the posted endpoint.

The registry describes planning illustrations based on a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not evidence of the trial’s design rationale or of observed power. The record does not report a sample-size justification, and planning calculations should not be interpreted as a retrospective probability that the trial detected an effect.

In general, planning sample sizes depend on assumptions about the target effect, variability, significance level, power, allocation, and analysis method. If the assumed effect is based on an observed effect, the resulting illustration is conditional on that observed estimate and may not represent a realistic target for a future study. The listed assumptions alone do not establish that these considerations were part of the original trial protocol. The statistical plan, interim analyses, and any prespecified methods beyond the posted descriptions are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("24-Week Treatment Group", "52-Week Treatment Group")
n      <- c(354, 73)
events <- c(5, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  24-Week Treatment Group  354  5  1.4  0.5  3.3  0.6  3.3  0.6  3.3
ARM  52-Week Treatment Group  73  3  4.1  0.9  11.5  1.4  11.4  1.5  11.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and zero analyses. It does not report a prespecified multiplicity strategy, such as a method for controlling error across multiple outcomes or comparisons. Without that information, the record does not show whether or how multiple testing was considered. The primary outcome can be described on its own, but no unreported adjustment should be assumed.

The registry record does not report a statistical analysis plan, interim analyses, or inferential results for the primary endpoint. It also does not report confidence intervals or p-values for the serious adverse event counts. The absence of such reporting should not be interpreted as evidence that a particular analysis was performed or that a result was statistically conclusive.

The analysis population for the primary outcome is not specified in the outcome description. The safety groups are reported with participants at risk, but the record does not explain in detail how participants with incomplete follow-up, discontinuation, or missing outcome information were handled. A missing-data method, imputation strategy, or sensitivity analysis is not reported in the registry record. The extent and pattern of missing safety data are also not reported.

These omissions limit assessment of how complete the endpoint data were and whether the posted counts represent all enrolled participants or a defined analysis population. They also limit evaluation of the robustness of the descriptive results. The observed counts remain interpretable as the figures reported for the listed groups and timeframes, but the record does not provide enough detail to extend them to a more complete statistical assessment.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intestinal obstruction (1.4%), abortion spontaneous (1.4%), ovarian mass (1.4%), visual impairment (0.3%), clavicle fracture (0.3%).

For serious adverse events, the registry reports 5 participants among 354 at risk in the 24-Week Treatment Group and 3 among 73 at risk in the 52-Week Treatment Group. Deaths are reported as 0 in each group. The outcome counts participants with serious adverse events, whether or not the event was related to study drug.

The registry also reports other adverse events for each group: 241 participants among 354 at risk in the 24-Week Treatment Group and 61 among 73 at risk in the 52-Week Treatment Group. These are not the primary serious-adverse-event outcome. The record lists Intestinal obstruction, Abortion spontaneous, and Ovarian mass at 1.4% each among the top serious terms; Visual impairment, Clavicle fracture, and Rib fracture are listed at 0.3% each.

These percentages and counts are registry descriptions, not evidence that INP104 caused the events. The groups have different follow-up windows, and the longer-duration group is a subset. Counts should not be compared as if they came from randomized groups observed for the same period. Zero recorded deaths means the registry lists none in these groups; it does not establish the absence of risk. The record does not provide detailed event-level narratives or a causal assessment.

13. What the Result Does, and Does Not, Mean

The posted results describe serious adverse events recorded during an open-label study of INP104. The primary measure is a count of participants with such events, with the event definition explicitly including cases whether or not they were considered related to study drug. The registry lists 5 participants with serious adverse events in the 24-Week Treatment Group and 3 in the 52-Week Treatment Group, alongside their respective at-risk group sizes and different endpoint timeframes.

Those results can support a descriptive account of reported safety events in the study population and during the specified follow-up. The accompanying serious-event terms offer some indication of the types of events listed in the record. Neither the counts nor the terms alone explain why events occurred, how they related to treatment, or whether similar events would have occurred without treatment.

The results do not establish that one treatment duration is safer than the other. The study was not randomized between the groups, the 52-Week Treatment Group is described as a subset, and the observation periods differ. No inferential comparison or precision interval for the primary endpoint is reported in the registry record. These limitations prevent a controlled interpretation of the apparent group counts.

The results also do not measure migraine improvement or establish treatment benefit. The primary endpoint is a safety outcome, and the registry record does not report a causal safety estimate. Likewise, the zero deaths recorded in each group should be read as a description of the posted data, not proof that the risk of death or other serious outcomes is absent. The appropriate conclusion is limited to what was recorded in this study, not a general claim about safety or effectiveness.

14. Why This Trial Matters Statistically

STOP 301 illustrates why a study’s design and outcome definition matter when interpreting safety counts. Its primary endpoint is a participant count for serious adverse events, which is straightforward to describe. However, the two reported duration groups have different follow-up windows, and the extended-treatment group is a subset rather than a randomized comparator. A simple numerical contrast cannot separate treatment duration from differences in exposure, follow-up, and participant selection.

The study also highlights the distinction between describing events and attributing them to treatment. The primary outcome includes serious adverse events whether or not they were related to study drug. This broad endpoint is useful for reporting events observed during the study, but it does not supply a causal estimate. The registry’s listed event terms add context without resolving attribution.

For biostatistical interpretation, the record is also a reminder that counts should be assessed alongside their denominators, timeframes, and uncertainty. Here, the registry reports the counts and at-risk groups but does not report a confidence interval, p-value, or inferential analysis for the primary outcome. The posted figures therefore support a descriptive reading, not a claim of a statistically demonstrated difference.

Finally, planning illustrations and observed trial results answer different questions. The listed planning assumptions describe a calculation framework, not the trial’s own sample-size rationale and not observed power. Distinguishing those concepts helps avoid overstating what a completed open-label safety study can establish from its registry record.

15. 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 study is open-label and has no randomized control group. Allocation is recorded as not applicable and masking as none. As a result, the duration groups are not a like-for-like comparison. The registry describes the 52-week treatment period as an extension for a subset, which may introduce selection differences that the posted summary does not address.

The endpoint windows differ: the 24-Week Treatment Group is followed through Week 26, while the 52-Week Treatment Group is followed through Week 54. The longer window allows more time for events to be recorded. The registry does not report a time-adjusted comparison or an analysis that accounts for these different follow-up periods.

The primary outcome counts participants with serious adverse events regardless of relationship to study drug. The record does not report a causal analysis or detailed clinical descriptions that would support an assessment of attribution. It lists zero deaths in each group, but the posted summary does not establish that rare outcomes are absent.

Several analysis details are not reported in the registry record, including a confidence interval or p-value for the primary outcome, a detailed analysis population, the handling of missing safety data, and the statistical analysis plan. Participant characteristics and detailed eligibility criteria are also not reported. These limitations constrain assessment of precision, generalizability, completeness, and causal interpretation. The results should therefore be read as registry-reported descriptive safety counts within the stated study groups and follow-up windows.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Tolerability of POD-DHE (INP104) in Migraine (STOP 301) — NCT03557333.
• Registry record last updated 2021-03-11; status last verified 2021-02.
• Results first posted 2021-02-12.
• 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.

19. Record Summary

STOP 301 is a completed, open-label, single-group Phase 3 study of INP104 in participants with migraine headache. The registry reports enrollment of 360 and describes a 24-week treatment period for all participants, with a 28-week extension for a subset and a 2-week post-treatment follow-up period.

The primary endpoint is the number of participants with serious adverse events, whether or not related to study drug. The registry reports 5 among 354 at risk in the 24-Week Treatment Group and 3 among 73 at risk in the 52-Week Treatment Group, with different follow-up windows. No randomized comparison or primary-outcome inferential analysis is reported. The counts are descriptive and do not establish causality or a comparative safety effect.