A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine (NCT03282227), a na phase 3 study. The primary outcome is Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months.

2. Clinical Question

3. Trial Design

This was a Phase 3, completed, open-label study of M207 for acute treatment of migraine. The registry describes a long-term safety study lasting up to 12 months. It began on 2017-11-07, and primary completion was recorded as 2019-05-17. The sponsor was Zosano Pharma Corporation.

The study used a single-group design rather than a randomized comparison. Allocation is listed as not applicable, masking as none, and no control group was included. Participants and study staff were therefore not masked to the study treatment, as reflected by the open-label design. The registry lists enrollment of 342, while the safety population included 335 participants who received any amount of study drug, meaning at least one patch was applied.

The intervention was M207 Microneedle System 3.8 mg, described as 1.9 mg per patch with two patches. After screening, participants entered a run-in period to record migraine activity. Qualified participants used the medication for multiple attacks, with an electronic diary used to confirm a qualified migraine and collect post-treatment responses. Application-site skin reactions were collected systematically through the diary and/or investigator skin assessment at study visits. Other adverse events were reported spontaneously by participants or observed on examination.

The primary safety outcome concerned the number of participants with any treatment-emergent adverse event over 12 months. The registry also lists attack-level secondary outcomes concerning pain freedom, most bothersome symptom freedom, pain relief, nausea freedom, photophobia freedom, and phonophobia freedom at 2 hours after dosing. Results for these secondary outcomes are not reported in the registry record. The record states that no statistical analyses were performed.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population included 335 subjects (98.0%) who received any amount of study drug (applied at least 1 patch).

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 population included 335 subjects (98.0%) who received any amount of study drug (applied at least 1 patch).

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months, measured over 0 to 12 months.

The primary endpoint is the number of participants in the safety population who had any treatment-emergent adverse event during the study timeframe of 0 to 12 months. The registry defines a treatment-emergent adverse event as a new adverse event that started after the first patch application. It reports 323 participants in the any-adverse-event count, with a safety population of 335 participants who received at least one patch.

This endpoint is used to describe the occurrence of adverse events after treatment exposure. A participant count is a direct descriptive measure of how many people met the endpoint definition in the safety population. It does not, by itself, establish that treatment caused an event: the definition specifies when an event began, while the open-label, single-group design has no control group for comparison. Nor does the count describe how often an individual experienced an event, how long events lasted, or their severity, unless those details are reported separately.

The endpoint is distinct from the listed attack-level secondary outcomes, which concern symptom responses after dosing. The registry record does not report results for those secondary outcomes. It also states that no statistical analyses were performed, so the primary endpoint is presented descriptively rather than as a modeled or adjusted comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, open-label study and states that no statistical analyses were performed. The primary outcome is a count of participants with any treatment-emergent adverse event. The posted information is therefore best understood as descriptive safety reporting, rather than as an inferential comparison between treatments.

What does a participant count represent?

A participant count indicates how many people in the defined analysis population met the endpoint definition. For this outcome, the safety population included participants who received any amount of study drug, operationalized as applying at least one patch. The endpoint counts participants with a new adverse event starting after first patch application during the study timeframe. The record reports 323 participants in the any-adverse-event count and identifies 335 participants in the safety population.

A count is not the same as an event total. One participant may have experienced more than one event, but the primary endpoint is framed around participants with any event. The registry record does not report event recurrence or the number of events per participant in the information. A participant count also does not convey duration, severity, or the clinical context of each event unless those are reported in additional detail.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. It can indicate which values are reasonably compatible with the observed data, rather than treating the point estimate as exact. A confidence interval does not correct limitations in study design, remove bias, or establish causation.

No confidence interval for the primary endpoint is reported in the registry record, and the record explicitly states that no statistical analyses were performed. Consequently, the posted count should not be interpreted as a model-based estimate with quantified sampling uncertainty. It is a descriptive result for the participants included in the stated safety population.

Why does the study design matter?

In general, a control group can provide a concurrent reference for interpreting outcomes, while random allocation can help make comparison groups similar in expectation. This study had no control group and was not a randomized comparison. It is recorded as single-group, with allocation listed as not applicable and masking listed as none. As a result, the data describe events observed during exposure in this study but do not estimate a treatment contrast against a concurrent alternative.

Open-label status is also relevant to interpretation. In general, awareness of treatment can affect reporting, observation, and assessment. The registry says application-site skin reactions were collected systematically through participant electronic diaries and/or investigator assessment at study visits, while other adverse events were spontaneously reported by participants or observed on examination. These different collection approaches are part of the outcome ascertainment context; the record does not report an analysis that adjusts for them.

How should the other outcomes be understood?

The registry identifies secondary outcomes concerning the percentage of migraine attacks with pain freedom, most bothersome symptom freedom, pain relief, nausea freedom, photophobia freedom, and phonophobia freedom at 2 hours after dosing. These are attack-level outcomes, unlike the primary endpoint’s participant-level count. In general, attack-level summaries depend on how attacks and their post-dose observations are defined and handled. The registry record does not report results for these secondary outcomes in the information, so no response estimates or uncertainty measures can be described.

In general, over-dispersion matters when observed variability exceeds what a statistical model expects. It can make standard errors too small if a model assumes less variability than the data contain. That issue is relevant to some repeated or clustered outcome data, but no such modeling or variance analysis is reported for this study. No model specification, adjustment method, or inferential procedure is reported in the registry record.

The record contains 7 outcome measures and lists 0 analyses. It explicitly states that no statistical analyses were performed for the primary safety outcome. A sample-size justification, interim analysis plan, and statistical analysis plan are not reported in the registry record. No claim about observed power or a prespecified analytical strategy can be drawn from the reported information.

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("M207 Microneedle System 3.8 mg")
n      <- c(335)
events <- c(323)
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  M207 Microneedle System 3.8 mg  335  323  96.4  93.8  98.1  93.8  97.9  93.8  97.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 7 outcome measures, including the primary safety endpoint and secondary outcomes concerning migraine-attack symptoms at 2 hours after dosing. The record lists 0 analyses and states that no statistical analyses were performed. A multiplicity adjustment or a strategy for controlling the risk of false-positive findings across outcomes is not reported in the registry record. Because secondary outcome results are not reported in the available record, no multiplicity-aware interpretation of those results is possible.

Missing-data handling is not reported in the registry record. The description does not specify how missing diary entries, incomplete follow-up, or unavailable adverse-event assessments were handled in the endpoint summaries. It also does not describe imputation, sensitivity analyses, or rules for participants who stopped treatment or left the study. These omissions limit assessment of whether the reported summaries could be affected by incomplete observation.

The primary outcome population is identified as the safety population, which included 335 participants who received any amount of study drug, defined as applying at least one patch. The registry lists enrollment of 342. The primary endpoint description refers to the safety population; a separate analysis population for the secondary outcomes is not reported in the registry record. The record does not report how participants outside the safety population were handled for other outcomes.

Because the study had no control group and no statistical analyses were performed, the main interpretive limits concern descriptive reporting, outcome ascertainment, and the completeness of follow-up information. Details of a sample-size justification, interim analyses, and a statistical analysis plan are not reported in the registry record.

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: hypokalaemia (0.3%), foetal disorder (0.3%), procedural pain (0.3%), breast cancer stage ii (0.3%), pneumonia (0.3%).

The registry lists 5 under serious adverse events for the M207 Microneedle System 3.8 mg group, with 335 participants at risk, and reports 0 deaths. The listed serious adverse-event terms are Hypokalaemia, Foetal disorder, Procedural pain, Breast cancer stage II, Pneumonia, and Asthma. Each term is paired with 0.3% in the record.

These figures are descriptive. The listed terms and percentages do not establish whether an event was caused by study treatment, and the study had no control group for comparison. The registry record does not provide a comparative estimate or statistical analysis for the serious-event figures. The listed categories should not be treated as a complete account of all event details, including timing, duration, or recurrence, unless such information is separately reported.

The count of 5 is reported under serious adverse events; it is distinct from the primary endpoint count of 323 participants with any treatment-emergent adverse event. The primary endpoint covers any new event starting after first patch application, while the serious-event summary is a separate safety listing. The record does not describe further analyses connecting these summaries.

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

The result describes treatment-emergent adverse events recorded among participants in an open-label, single-group study of M207 for acute migraine treatment. The registry reports 323 participants with any treatment-emergent adverse event in a safety population of 335. The endpoint counts new adverse events that started after first patch application over the 0 to 12 months timeframe. The registry separately lists 5 under serious adverse events and 0 deaths.

These results can be used to understand what was recorded during the study in the defined safety population. They do not show how event occurrence compares with a control group, because none was included. They also do not establish that treatment caused an event simply because it began after treatment started. The record describes timing as part of its endpoint definition, not as proof of causation.

The reported counts do not, by themselves, describe event severity beyond the separate serious-event listing, how long events lasted, whether participants had repeated events, or how events varied over the observation period. No confidence interval or statistical analysis for the primary endpoint is reported. The results therefore do not quantify statistical uncertainty around the count or support an adjusted comparison.

The study also lists secondary outcomes concerning migraine symptoms at 2 hours after dosing, but their results are not reported in the registry record. The safety endpoint does not answer those symptom questions. Likewise, the study’s design and results do not establish a comparative treatment effect. The appropriate reading is limited to the descriptive safety information and the population and timeframe defined in the registry.

14. Why This Trial Matters Statistically

This study illustrates why the design and analysis context matter when reading safety results. A participant count can describe what was observed in a defined safety population, but its meaning depends on the endpoint definition, how events were collected, and who was included. Here, the primary endpoint counts participants with a new adverse event beginning after first patch application, and the safety population consists of those who received any amount of study drug.

The study’s open-label, single-group design is central to interpretation. Without a control group, the safety counts do not provide a concurrent reference for judging whether event occurrence differs under another treatment or without study treatment. The record also states that no statistical analyses were performed. Readers should therefore distinguish a descriptive count from a comparative estimate or a causal conclusion.

Outcome collection was not identical for all event types: application-site skin reactions were collected systematically through electronic diaries and/or investigator assessments, while other adverse events were spontaneously reported or observed on examination. That distinction helps explain how the endpoint information was gathered and is relevant when considering how completely different event types may have been captured.

The record’s limits are also informative. It identifies secondary attack-level symptom outcomes but does not report their results in the information. It does not report a statistical analysis plan, missing-data methods, or multiplicity procedures. Recognizing what is recorded and what remains unreported helps keep conclusions aligned with the evidence: the trial offers descriptive safety observations, not a randomized comparison or a complete account of comparative efficacy.

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 absence of a control group is a major limitation for comparative interpretation. The study is single-group, open-label, and not a randomized comparison. Consequently, the registry results describe events observed among participants who received study drug but do not provide a concurrent estimate for another treatment or no study treatment. The design cannot separate treatment-related effects from background events through a controlled contrast.

The primary endpoint is based on whether a participant had any new adverse event after first patch application. A binary participant-level count does not show the number of events per participant, their duration, or their distribution over time. The registry record does not report those details in the information, and it does not report a confidence interval or statistical analysis for the endpoint.

Ascertainment differed by event type. Application-site skin reactions were collected systematically through participant electronic diaries and/or investigator skin assessment at study visits. Other adverse events were spontaneously reported by participants or observed upon examination. The record does not report an analysis of how these collection approaches may affect event capture.

The registry does not report missing-data handling, a sample-size justification, interim analyses, or a statistical analysis plan. Results for the listed secondary outcomes are not reported in the registry record, and multiplicity procedures are not reported. These gaps constrain assessment of completeness, uncertainty, and the intended analytical framework. The safety findings should be interpreted within the stated safety population and the study’s 0 to 12 months timeframe.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine — NCT03282227.
• Registry record last updated 2020-08-19; status last verified 2020-08.
• Results first posted 2020-08-19.
• 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

NCT03282227 is a completed Phase 3, open-label, single-group study of M207 Microneedle System 3.8 mg for acute migraine treatment. The registry lists enrollment of 342 and a safety population of 335 participants who received at least one patch. The study began on 2017-11-07, and primary completion was recorded as 2019-05-17.

The primary endpoint counted participants with any treatment-emergent adverse event over 0 to 12 months. The registry reports 323 in the any-adverse-event count, 5 under serious adverse events, and 0 deaths. It states that no statistical analyses were performed and identifies no control group. Secondary outcomes concerned migraine symptoms at 2 hours after dosing, but their results are not reported in the registry record.