A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine (NCT04153409), a randomized phase 2 study. The primary outcome is Change in Migraine Headache Pain Score From Time of Dosing (0 Minutes).

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, placebo-controlled, quadruple-masked crossover proof-of-concept study of oral LAT8881 for acute migraine. The registry lists enrollment of 21 and a completed status. The recorded start date is 2019-09-24 and the primary completion date is 2020-02-15. These dates describe the study record; they do not supply outcome findings.

In a crossover design, participants can receive more than one study treatment in separate periods, allowing comparisons that use information from the same participant under different treatments. That general feature can make within-person comparisons informative because stable differences between people do not necessarily drive the treatment contrast. The registry record does not report the treatment sequence, period structure, washout interval, or how any period effects were addressed. It is therefore not possible to assess those design details from the record.

Randomization is intended to reduce systematic differences in treatment assignment. Masking is intended to limit the influence of expectations or knowledge of assigned treatment on participant experience, study conduct, and outcome assessment. The record labels the study quadruple-masked but does not specify which roles were masked or how masking was maintained.

For the active treatment, participants were instructed to take two 30 mg capsules within the first hour of a moderate-to-severe migraine onset. The placebo instructions used two capsules with the same timing and symptom-intensity description. The registry record does not report adherence, treatment sequence, discontinuations, or the number of participants who completed each treatment period.

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

Analysis population for the primary outcome, as defined in the registry: Per protocol population

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 Change in Migraine Headache Pain Score From Time of Dosing (0 Minutes), measured over 0 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours and 24 hours post dose.

The primary endpoint was change in migraine headache pain score from the time of dosing, defined as 0 minutes. Pain was recorded in a subject diary using an 11-point numeric rating scale, with 0 representing no pain and 10 the worst imaginable pain. The record states that a lower score indicates less pain intensity. The scheduled assessment times were 0 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours and 24 hours post dose.

Change from a starting measurement is used to describe how a continuous measure moves over time relative to its reference point. It can make the direction and magnitude of within-person symptom movement easier to interpret than an isolated follow-up score. In this trial, the endpoint concerns headache pain intensity, not every migraine symptom or a global judgment of recovery. The secondary outcomes separately concern nausea, photophobia, phonophobia, each subject's most troublesome symptom, and achieving no headache pain.

The record identifies the primary measure as a mean with standard deviation and names the per-protocol population. It does not report the observed mean changes, standard deviations, treatment contrast, confidence interval, or p-value at any assessment time. Without those results, the endpoint definition alone cannot show whether pain scores changed differently under LAT8881 and placebo, or how precisely any contrast was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary measure summarized as a mean and standard deviation. A mean represents the average value in a group or set of observations. A standard deviation describes how dispersed observations are around that mean. The two quantities answer different questions: the mean locates the center, while the standard deviation describes variability among measurements. Neither quantity is reported for the primary outcome in the registry record.

What does change from baseline mean?

Change scores compare a later measurement with a reference measurement. Here, the reference is the pain score at dosing, defined as 0 minutes, and later diary scores were planned at several post-dose times. A negative or positive change has meaning only with the scale direction and subtraction convention clearly stated. The record says that a reduction in the numeric rating scale score indicates reduced pain intensity, but does not provide the actual changes or detail how the change values were calculated for the reported analyses.

Why does a crossover design matter?

In general, a crossover trial compares treatment experiences within the same participant across separate periods. This can account for some stable between-person variation because each participant can serve as their own reference. It also makes period order and timing important. Symptoms may vary over time, and treatment effects could potentially carry into a later period. A washout interval, treatment sequence, period-specific analyses, and handling of carryover are relevant design details. They are not reported in the registry record, so the suitability of any particular crossover analysis cannot be assessed.

Repeated measurements can be analyzed in several ways. A method might compare change at a prespecified time, assess several times separately, or model the repeated observations together. Those approaches can differ in assumptions and in the way they use incomplete records. The registry record does not describe the statistical model, covariance assumptions, handling of repeated measures, or the exact contrast used. It would be inappropriate to attribute any of these approaches to this trial without a report of the analysis plan.

What do a confidence interval and a p-value convey?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the method. Its width conveys precision: a wider interval indicates less precision than a narrower one. A p-value summarizes how unusual the data would be under a specified null hypothesis and statistical model. It does not give the probability that a treatment works, and it does not measure the size or clinical importance of an effect. No primary-outcome confidence interval or p-value is reported in the registry record.

Statistical significance and practical importance are distinct. A small estimated difference can be estimated precisely, while a potentially important difference can remain uncertain when data are limited. Judging either requires the estimated contrast, uncertainty, and a clinically meaningful context. The registry record does not report a threshold for meaningful change or the estimates needed to make that assessment.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a model understates variability, its uncertainty estimates can be too small and its tests too optimistic. This issue is most familiar in count-data models, and it is not a claim about the continuous pain-score analysis in this trial. The registry record does not report an over-dispersion assessment or any model diagnostics.

The record lists a mean and standard deviation for the primary measure but does not state whether the final inference used a model, a direct comparison, or another method. It also does not report covariate adjustment, treatment-period adjustment, or how repeated observations from the same participant were accounted for. These distinctions matter because observations from one participant are generally not independent of one another. A valid analysis needs to reflect the design and the data structure; the exact method used is not reported in the registry record.

Planning illustrations based on an observed effect are conceptually different from observed trial findings. Such illustrations depend on assumptions about the significance level, allocation, distributional approximation, and the fraction of an observed effect one wishes to detect. The registry record states assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation for the planning illustration. It does not report a trial-specific sample-size justification, and the illustration should not be read as observed power or as evidence that the study was adequately sized.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was measured at several post-dose times, and the registry lists multiple secondary outcomes. Testing treatment differences repeatedly can increase the chance of obtaining a seemingly notable result by chance if no allowance is made for the number of comparisons. In general, multiplicity approaches include defining a hierarchy of tests, adjusting significance thresholds, or treating analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among outcomes or time points, or which comparisons were prespecified for formal inference.

The record identifies the per-protocol population for the primary outcome, but does not report the population definition, analysis size, or whether other analysis populations were used. It does not report how protocol deviations, incomplete treatment periods, or participants with no usable diary measurements were handled. The amount and pattern of missing outcome data are not reported in the registry record.

Missingness can affect interpretation when the likelihood of an unrecorded measurement relates to symptoms, treatment experience, or other factors. Complete-case analyses, imputation, and model-based approaches each rely on assumptions, and different assumptions can lead to different estimates. These are general considerations, not a description of methods used in this study. The registry record does not report a missing-data method, sensitivity analysis, or assessment of the assumptions behind any such method.

Because this is a crossover study, missing data may also differ across treatment periods or assessment times. The record does not explain how incomplete paired treatment observations were handled. Consequently, the effect of missingness on the reported comparison cannot be evaluated from the registry record.

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 registry record lists 17 participants at risk in the Active group and 17 in the Placebo group for both serious and other adverse events. It records zero serious adverse events in each group and 3 participants affected by other adverse events in each group. No serious adverse-event terms are listed.

These are counts as recorded, not a complete account of the types, timing, duration, or severity of all events. The record does not identify the other adverse events, say whether any led to treatment discontinuation, or describe how participants exposed to both treatments in a crossover design were assigned to safety groups. The at-risk counts should not be treated as the total enrolled population or as the number analyzed for efficacy.

Zero recorded serious events does not establish that the risk is absent. Counts from a small study can be imprecise, and this record does not provide uncertainty estimates for safety outcomes. The equal recorded counts of participants affected by other adverse events do not by themselves establish equivalence between treatments. Exposure, event definitions, event timing, and fuller safety data would be needed for a more detailed comparison. These figures are descriptive registry entries, not a basis for medical advice.

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

The trial record asks a focused question about oral LAT8881 for acute migraine and defines a diary-based pain measure over a sequence of post-dose times. It also identifies placebo as the comparator and describes randomized, quadruple-masked, crossover conduct. Those details clarify the intended comparison and the planned measurement, but they do not reveal the outcome.

The registry record does not report primary endpoint values, treatment contrasts, confidence intervals, or p-values. As a result, it cannot show whether the posted pain scores favored either treatment, how large a difference may have been, or how precisely a difference was estimated. The absence of reported efficacy results is not evidence that there was no effect; it means the effect cannot be evaluated from this record.

The listed safety counts are limited descriptive information. They record no serious adverse events and 3 participants affected by other adverse events in each group, among 17 at risk in each. They do not characterize the events or establish that the safety experience was the same. A small proof-of-concept study can provide information about study conduct and generate questions, but its design label alone does not establish efficacy or safety.

Interpretation also depends on information not reported in the registry record, including the full analysis plan, handling of repeated measurements and crossover periods, participant flow, missing data, and multiplicity. These details affect how the estimates should be understood. No treatment recommendation follows from the available information. The record supports a precise description of what was planned and which safety counts were entered, while leaving the primary treatment comparison unresolved.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a crossover design with repeated symptom measurements after treatment of an acute episode. A crossover structure can support within-person comparisons, while the sequence of post-dose diary assessments can describe symptom trajectories. Both features also create analytical requirements: treatment period, sequence, within-person dependence, and repeated observations may need to be considered. The registry record does not report how these features were addressed in analysis.

The endpoint is continuous and has an explicitly described scale, which makes the direction of score movement interpretable. At the same time, the primary measure is assessed at multiple times. Multiple assessments can answer different clinical questions, such as early change or later persistence, but they also raise the question of which comparisons were intended to carry confirmatory weight. The registry record does not report how that issue was handled.

The record also illustrates the distinction between a study plan and evidence about an effect. A clearly specified outcome and design do not replace estimates and uncertainty. Since primary results are not reported, the numerical treatment comparison cannot be assessed. Similarly, the safety counts offer a limited description but not a precise comparative safety analysis.

For readers evaluating clinical trial statistics, the main lesson is to separate design information, outcome definitions, and observed results. Here, the first two are described, while the primary outcome findings and key analytic details are not reported in the registry record. That boundary limits conclusions regardless of the study's phase or proof-of-concept purpose.

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 principal limitation for interpretation is that the registry record does not report numerical results for the primary pain-score endpoint. It gives no means, standard deviations, treatment contrasts, confidence intervals, or p-values at the scheduled assessment times. Efficacy and precision therefore cannot be assessed.

Enrollment was 21, while the primary endpoint is specified for the per-protocol population. The number contributing to the primary analysis, participant flow, treatment completion, and outcome completeness are not reported in the registry record. This prevents assessment of how closely the analyzed population matches enrollment and whether missing observations may have affected the findings.

Important crossover details are also absent, including treatment sequence, period structure, washout, and handling of potential period or carryover effects. The statistical model, repeated-measure handling, multiplicity strategy, and missing-data methods are not reported. Without these details, the robustness of any primary comparison cannot be evaluated.

The safety information is restricted to counts of serious and other adverse events. Event descriptions, exposure details, timing, and the basis for group attribution are not reported. The registry record also does not give a detailed sample-size justification or interim-analysis plan. No such design or analysis details should be inferred from the trial's phase or proof-of-concept description.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine — NCT04153409.
• Registry record last updated 2021-04-28; status last verified 2021-04.
• Results first posted 2021-03-30.
• 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

NCT04153409 is a completed phase 2 randomized, quadruple-masked, placebo-controlled crossover proof-of-concept study of oral LAT8881 for acute migraine, with or without aura. The registry lists enrollment of 21. Active-treatment instructions specified two 30 mg capsules within the first hour after onset of a moderate-to-severe migraine; placebo instructions used two capsules on the same schedule.

The primary outcome was change in migraine headache pain score from dosing, measured on an 11-point numeric rating scale at multiple post-dose times, in the per-protocol population. Numerical primary results and key analysis details are not reported in the registry record. Safety entries list 17 at risk in each group, zero serious adverse events in each, and 3 participants affected by other adverse events in each.