Therapy for Migraine Prevention in Children 6-11 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Therapy for Migraine Prevention in Children 6-11 Years of Age (NCT04050293), a randomized phase 4 study. The primary outcome is Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine..

2. Clinical Question

3. Trial Design

The registry record describes a phase 4 randomized, quadruple-masked, parallel-group study of SPN-538 and placebo. Its official title identifies it as a multicenter study. The planned comparison was between participants assigned to SPN-538 and participants assigned to placebo, with migraine prevention in children ages 6 to 11 as the clinical focus. The record lists an enrollment of 26 participants.

The study began on 2020-07-14, and the primary completion date is listed as 2023-03-01. Its current status is terminated. The reason for termination and the timing of the termination relative to primary completion are not reported in the registry record. The record does not state whether the enrollment reached a target or whether a particular operational or scientific reason led to termination. These details should not be inferred from the status alone.

The intervention is identified as SPN-538, with the arm description specifying a topiramate XR capsule; the other arm received placebo. The registry record does not report treatment dose, titration instructions, adherence, or the actual exposure duration for participants. The primary endpoint description refers to a 20-week double-blind treatment phase, but this does not establish how long each participant remained in treatment.

Randomization is listed, but the method used to generate the allocation sequence, the allocation ratio, and any stratification factors are not reported in the registry record. Quadruple masking is recorded, while the identities of the masked roles are not specified. The record also does not report details of recruitment, participating centers, eligibility criteria beyond the age and migraine framing, or the planned sample-size justification. The design label alone cannot fill in these protocol details.

The record lists one primary outcome measure and no posted analyses. As a result, the design can be described, but the intended between-arm estimate cannot be evaluated from reported efficacy results. The record’s terminated status is relevant context, but it does not itself indicate the direction or size of any treatment effect.

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: Total of 60 participants were screened for eligibility; 26 participants randomized to receive double-blind treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included participants who received at least one dose of study medication and have a baseline and at least one valid post-baseline assessment of monthly migraine based on the headache diary data. The number of participants in some rows differs from the overall number as some participants discontinued the study before the specific time points.

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 includes all randomized participants who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine., measured over Baseline, Titration Period 1 (Month 1), Titration Period 2 (Month 2), Maintenance Period 1 (Month 3), Maintenance Period 2 (Month 3), Maintenance Period 2 (Month 4) and Maintenance Period 3 (Month 5).

The primary endpoint is change from baseline in monthly migraine days in children ages 6 to 11 with migraine. It is a continuous measure summarized as a mean, with standard deviation named as the dispersion measure. The endpoint description defines the primary efficacy measure as change in the rate of monthly migraine days relative to the prospective baseline period.

The 28-day rate is defined using migraine days during the last four weeks of the prospective baseline period and non-missing headache diary days during the last four weeks of the 20-week double-blind treatment phase, scaled to a 28-day rate. The endpoint was recorded using a headache electronic diary uploaded through a patient-reported outcome application. The registry describes the diary as the primary tool for collecting daily headache information.

Using a rate expressed on a common 28-day basis can make diary periods with different numbers of recorded days more comparable. More generally, repeated daily records can capture changes in symptom frequency over time that a single retrospective report may not represent as directly. Those are general measurement considerations; the registry record does not establish how complete or reliable the diary data were in this study.

The listed timeframe includes baseline and titration and maintenance periods, with the registry wording naming Titration Period 1 (Month 1), Titration Period 2 (Month 2), Maintenance Period 1 (Month 3), Maintenance Period 2 (Month 3), Maintenance Period 2 (Month 4), and Maintenance Period 3 (Month 5). No endpoint values at these timepoints are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be identified from the registry record are the randomized, masked, parallel-group design and the continuous primary endpoint. The endpoint is a mean change in monthly migraine days, with standard deviation specified as its dispersion measure. The record does not report a detailed statistical analysis plan, so the exact model, covariates, handling of repeated measurements, or method for comparing arms is not reported in the registry record.

What does a mean represent?

In general, a mean is the arithmetic average of the values included in an analysis. For a change-from-baseline endpoint, the value for a participant is based on a post-baseline measure relative to that participant’s baseline measure; an arm-level mean then summarizes the participant-level values used in the analysis. A mean is useful for describing the average change, but it can be influenced by unusually large or small observations. It should therefore be read with information about variability and uncertainty, not as a complete description of every participant’s experience.

The standard deviation describes the spread of observed values around a mean. It is not the same as the uncertainty in the estimated mean or in a between-arm contrast. The standard error and confidence interval are ways to express uncertainty in estimates, but the registry record does not report either for this outcome. No variation or uncertainty can be reconstructed from the enrollment total alone.

Why express diary counts as a rate?

The endpoint description uses a 28-day rate and accounts for the number of days with non-missing diary records in the treatment-period denominator. In general, this approach places diary data on a common time basis when the number of recorded days may vary. It can make the measure easier to interpret as migraine frequency over a standard period. It does not, by itself, eliminate bias that could occur if diary completion is related to migraine symptoms, treatment, or other participant characteristics. The registry record does not report diary completion rates or analyses of missing diary data.

The endpoint is described as a change relative to the prospective baseline period, while its rate definition compares the baseline diary period with the end-of-treatment diary period. The record lists several titration and maintenance timepoints as part of the outcome timeframe. Repeated measurements may be analyzed in different ways, for example by comparing a prespecified timepoint or by modeling measurements across time. Those are general possibilities, not claims about this trial’s analysis. The actual approach is not reported in the registry record.

How should a treatment comparison be read?

A randomized comparison is intended to contrast outcomes between assigned groups. In general, randomization can help balance measured and unmeasured participant characteristics across groups at assignment, but it does not guarantee balance in a small enrolled sample, nor does it correct problems arising after assignment such as missing outcomes. A sound interpretation depends on the analysis population, the way missing data are handled, and the estimate’s uncertainty. The registry record identifies a Full Analysis Set definition but does not report the number analyzed or the model used.

A confidence interval would help show the range of treatment differences reasonably compatible with the data under the analysis assumptions. A p-value addresses compatibility with a null hypothesis, not the size or clinical meaning of the contrast. These general interpretations cannot be applied to a trial-specific estimate because no efficacy estimate, interval, or p-value is reported. No claim about benefit, lack of benefit, or equivalence can be drawn from an absent analysis.

What can sample-size calculations tell readers?

Sample-size calculations are planning exercises: they assess how many participants might be needed under specified assumptions about the effect, variability, significance level, allocation, and statistical method. They are not a measure of the probability that a completed study found a true effect. In particular, planning illustrations should not be described as observed power. The registry record does not report a sample-size justification for the trial, and no trial-specific planning assumptions beyond the stated generic illustration assumptions are available for evaluation. Without posted outcome estimates, the assumptions behind an effect-based planning illustration cannot be checked against reported efficacy results.

More generally, a statistical test’s result depends on both the estimated effect and its uncertainty. A small estimate with a narrow interval and a larger estimate with a wide interval can lead to different interpretations even if a single significance label were similar. Statistical significance, when available, does not automatically convey practical importance. For this study, the registry record contains no inferential result to interpret, so these concepts serve only as general guidance for reading a future or separately reported analysis.

Finally, no analysis of over-dispersion is reported. In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes; if unaccounted for, uncertainty estimates can be too small. Whether that issue is relevant depends on the model and data structure. Since the registry record does not identify the fitted model or report participant-level endpoint data, it is not possible to assess over-dispersion or determine whether any adjustment was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, but it describes several periods and timepoints within that outcome. It does not identify a single reported comparison across those periods, and no primary efficacy analysis is posted. The record does not describe a hierarchy of hypotheses, an adjustment for multiple comparisons, or a strategy for selecting among timepoints. These multiplicity details are not reported in the registry record.

Multiplicity matters generally when several outcomes, timepoints, or subgroup comparisons are tested. More opportunities to identify a nominally unusual result can increase the chance of a false-positive finding if the analyses are treated as independent tests without an appropriate plan. This is a general concern, not a claim that any particular multiplicity procedure was needed or omitted in the trial. The available record is insufficient to determine how the investigators intended to control or interpret multiple testing.

The Full Analysis Set is defined as participants who received at least one dose and had a baseline and at least one valid post-baseline assessment based on headache diary data. The record does not report how many participants met this definition, how the analysis population differed from the randomized groups, or whether other populations were used. A participant count in some rows is noted to differ from the overall number, but the explanation is incomplete in the registry record.

Missing-data methods are also not specified. The endpoint rate uses the number of non-missing headache diary days in its denominator, but the record does not report diary completion by arm or timepoint, reasons for missing entries, or any imputation or sensitivity analysis. In general, using recorded days in a rate calculation does not establish that unrecorded days are comparable to recorded days. Missingness can affect interpretation if it is related to symptoms or treatment. Without the missing-data details and results, the robustness of any endpoint estimate cannot be assessed.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event entries list 13 participants at risk in the placebo group and 13 in the SPN-538 group. Zero participants are listed as affected by serious adverse events in either group. The death count is zero in both groups. For other adverse events, four participants are listed as affected in each group, with 13 at risk in each group.

These figures are counts in the registry record, not estimates of comparative risk adjusted for follow-up time or other factors. The record does not provide event descriptions for serious adverse events, and the list of top serious event terms is empty. It also does not report the duration of observation, the number of events per affected participant, severity or relatedness for the other adverse events, or whether adverse-event collection was complete for all participants.

Equal counts across the groups do not establish equal safety profiles. Counts can be imprecise in a small study, and interpretation depends on definitions, follow-up, event details, and data completeness. The figures should be read as the posted safety counts only; they do not establish a treatment effect on safety or address risks not captured in the record.

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

The registry record establishes that a randomized, placebo-controlled study of SPN-538 for migraine prevention in children ages 6 to 11 was registered and that its primary endpoint concerned change in monthly migraine days. It also records an enrollment of 26, a terminated status, and safety counts for serious and other adverse events. These are relevant details about the study record, but they do not provide an efficacy result.

The primary outcome is not accompanied by arm-level values or a comparative analysis. As a result, the posted results do not show the magnitude or direction of change in monthly migraine days for either group, the difference between groups, or the precision of that difference. There is no confidence interval or p-value to interpret. The absence of those results does not establish that SPN-538 did or did not change migraine frequency relative to placebo.

The listed safety counts are limited to the events recorded in the registry. They show zero serious adverse events and zero deaths in each group, alongside four participants with other adverse events in each group. They do not describe event types or observation time and cannot establish that the groups had equivalent safety outcomes.

More broadly, a registered endpoint is not the same as a reported result. Evaluation of an efficacy finding would require the outcome values, analysis population, statistical method, and uncertainty estimates. Interpretation would also depend on missing diary data, timepoint selection, and any prespecified handling of multiple analyses. Those details are not reported in the registry record. The termination status alone gives no basis for attributing a reason or inferring an outcome. The appropriate statistical reading is therefore limited: the intended question and broad design are identifiable, while the primary treatment comparison remains unquantified in the posted results.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry record specifies a continuous diary-based endpoint but does not include the corresponding efficacy analysis. The distinction between an endpoint definition and an endpoint result is central to evidence appraisal. A detailed outcome description can explain what investigators intended to measure, but without numerical results it cannot answer whether the randomized groups differed or how precisely any difference was estimated.

The study also illustrates why an overall enrollment figure is not enough to judge the information available for a primary analysis. The endpoint population required at least one dose, a baseline assessment, and a valid post-baseline diary assessment. The number meeting these criteria is not reported. Nor are the numbers contributing data at each listed timepoint. For repeated diary outcomes, both the number of participants and the completeness of their observations matter to interpretation.

The diary-based rate has a clear measurement purpose: it expresses migraine frequency over a 28-day basis while using non-missing diary days in the denominator. General statistical reasoning also highlights a limitation: rate scaling does not remove concerns about selective diary completion. The record does not provide the completion information needed to assess that issue.

Finally, a terminated study with no posted efficacy analysis cannot be classified from its status alone as positive, negative, or inconclusive in the statistical sense. The record contains no treatment-effect estimate, uncertainty interval, or analysis plan to support such a classification. Keeping those distinctions explicit helps prevent a design description or a safety count from being mistaken for evidence about the primary efficacy question.

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 most consequential limitation of the available record is the absence of posted efficacy analyses for the primary endpoint. No mean changes, between-group estimate, uncertainty interval, or inferential result is reported. This prevents assessment of effect direction, size, and precision and means the trial’s primary question cannot be answered from the registry results.

The enrollment is listed as 26, but the primary endpoint’s Full Analysis Set count is not reported. The numbers contributing to each listed timepoint are also not available. The registry’s note that some row counts differ from the overall number is incomplete, so the reasons for those differences cannot be determined. Participant characteristics, baseline migraine frequency, diary completion, and treatment adherence are not reported in the registry record.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record also does not establish whether termination affected recruitment, follow-up, or analysis. The primary completion date is listed, but that date does not by itself explain how the study proceeded or why it ended.

Further trial-specific limitations include absent detail on allocation procedures, masking roles, treatment dosing, missing-data handling, model choice, multiplicity, and the statistical analysis plan. The endpoint timeframe names several periods, including Maintenance Period 2 at both Month 3 and Month 4; the registry wording does not clarify this. Safety details are limited to counts, without event descriptions or observation duration. These gaps restrict interpretation of both efficacy and safety and should not be filled by assumptions about the protocol or conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Therapy for Migraine Prevention in Children 6-11 Years of Age — NCT04050293.
• Registry record last updated 2026-01-22; status last verified 2025-12.
• Results first posted 2025-11-21.
• 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.

18. Record Summary

This phase 4 study evaluated SPN-538 for migraine prevention in children ages 6 to 11, with placebo as the comparator. The record describes a randomized, quadruple-masked, parallel-group, multicenter study and lists enrollment of 26. The study began on 2020-07-14, has a primary completion date of 2023-03-01, and is marked terminated.

The primary endpoint was change from baseline in monthly migraine days, assessed using headache electronic diary data and expressed as a 28-day rate. The Full Analysis Set required at least one dose, baseline data, and at least one valid post-baseline assessment. No primary efficacy analyses are posted, and the number included in that endpoint population is not reported in the registry record.

Serious adverse events and deaths are listed as zero in each group; four participants in each group are listed with other adverse events. These counts do not resolve the unanswered efficacy question. The registry record does not report the reason for termination or the detailed statistical plan.