A Study of Lasmiditan in Healthy Japanese and Caucasian Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Lasmiditan in Healthy Japanese and Caucasian Participants (NCT03579940), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration.

2. Clinical Question

The study addressed safety, tolerability, and pharmacokinetics of lasmiditan in healthy Japanese and Caucasian participants. Its primary outcome was the number of participants with one or more serious adverse events considered by the investigator to be related to study drug administration, from baseline up to Day 20. The registry also lists pharmacokinetic outcomes for lasmiditan, including area under the concentration-versus-time curve from zero to infinity and maximum observed concentration in each period.

This is a safety and pharmacokinetic study in healthy participants, not a trial of clinical benefit in a patient population. The posted primary result is a count rather than an estimated treatment effect from a single placebo-versus-lasmiditan comparison. Because the design is crossover and includes multiple dose periods, a participant may contribute to more than one listed exposure group. The registry record does not report a single pooled contrast between lasmiditan and placebo.

3. Trial Design

The registry identifies this as a Phase 1, randomized, double-blind, crossover study. It records a total enrollment of 27 and a completed status. The study began on 2018-06-27, and primary completion was recorded as 2018-08-09. Participants were healthy Japanese or Caucasian individuals. The study description says participation could last up to 47 days for each participant.

The intervention descriptions indicate oral study drug administration across study periods. Japanese participants had listed single-dose lasmiditan regimens of 50 mg, 100 mg, 200 mg, and 400 mg, as well as a repeated 2 × 200 mg regimen. Caucasian participants had listed single doses of 50 mg, 100 mg, and 200 mg. Placebo regimens were also listed, including repeated placebo for Japanese participants. The descriptions say participants received treatments in up to three study periods; they do not give a complete sequence schedule or period-level allocation details.

A crossover design means treatment comparisons can involve observations from the same participants across different periods. That structure differs from a parallel-group design in which each participant remains in one treatment group. Consequently, the exposure-group counts in the registry should not be treated as mutually exclusive participant groups or added to infer a unique-participant total. The record does not report the randomization sequence, washout details, or how period and sequence effects were handled in statistical analyses.

The sponsor is Eli Lilly and Company. The registry lists lasmiditan and placebo as drug interventions. The stated study purpose was to evaluate safety and tolerability and to investigate the amount of lasmiditan entering the bloodstream and how long it takes the body to eliminate it. The record does not report a detailed statistical analysis plan or a sample-size justification.

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: Crossover study with three study periods, each participant received single/repeated oral doses of 50, 100, 200, 400, or 2 X 200 milligram (mg) lasmiditan, placebo, or 2 X placebo, according to their assigned treatment sequence, on Day 1 of each Period. The washout period between dosing in consecutive study periods was approximately 72 hours.

Only the first 6 of 11 groups are shown.

Period 1

Period 2

Reasons for not completing this period:

Period 3

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of study drug.

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: All enrolled participants who received at least one dose of study drug.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration, measured over Baseline up to Day 20.

The primary endpoint counts participants who had one or more serious adverse events that the investigator considered related to study drug administration. The registry defines the observation window as baseline up to Day 20 and identifies the population as enrolled participants who received at least one dose of study drug. A participant with multiple qualifying events is counted as a participant with an event, rather than contributing a separate count for each event.

Serious adverse events are tracked in clinical studies because their severity makes them important for safety monitoring. Restricting this endpoint to events considered related by the investigator adds a causal-attribution judgment to the event classification. That judgment is not the same as demonstrating that a drug caused an event. The registry describes separate adverse-event summaries that include serious and other non-serious events regardless of causality.

The primary measure is a count, not a continuous measurement or a time-to-event estimate. Counts are useful for describing whether any participants in an exposure group experienced the defined event during the stated window. They do not, on their own, quantify the timing, recurrence, clinical course, or severity of each event. The record does not provide event-level descriptions for this primary outcome.

The posted primary counts are zero for each listed exposure group. With no observed events in those groups, the posted result describes what was recorded during the study; it does not establish that the underlying risk is zero. Precision is limited by the small exposure-group counts and by the absence of a posted comparative estimate with an uncertainty interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: a participant either had one or more serious adverse events considered related to study drug administration during the stated timeframe or did not. The reported statistic is a count in each listed exposure group. Counts are direct descriptions of recorded events; they are not adjusted effects, model estimates, or evidence of a statistically significant difference.

What does a zero count convey?

A zero count says that no participants in the reported group met the endpoint definition in the observation window. It is not the same as proving that the event is impossible or that the underlying event probability is zero. General statistical explanation: data from a finite number of observations leave uncertainty about the rate that would be seen in a broader population. When events are rare, that uncertainty can remain substantial even when no events are observed.

The record gives no confidence interval or other uncertainty interval for the primary outcome. A confidence interval is a range calculated by a statistical method to describe uncertainty around an estimate under that method’s assumptions. Without a posted interval or analysis, the zero counts should be read descriptively rather than as precise estimates of risk.

Why is a two-arm comparison unavailable?

The registry indicates that values are missing or not estimable for a two-arm comparison of this binary endpoint. It does not post a comparative estimate, test statistic, or p-value for the primary result. The study has multiple dose-specific exposure groups and a crossover design, rather than one straightforward lasmiditan group and one mutually exclusive placebo group. Participants may contribute observations across periods, so treating all listed exposure counts as independent parallel groups would not reflect the described design.

General statistical explanation: a comparison requires a clearly specified contrast and an analysis that accounts for how observations were collected. In a crossover study, within-participant relationships and period structure may matter. The registry record does not report the method used to account for those features, so no such adjustment or comparison can be inferred from the displayed counts alone.

How should repeated exposure counts be understood?

The arm descriptions refer to study periods and to single or repeated dosing. Counts differ across the listed groups, and a participant may contribute to more than one exposure group. These counts therefore describe the number of participants represented in each reported exposure category, not separate group sizes that can be added to obtain the number of unique participants. The registry records enrollment of 27, but the exposure-specific counts should not be summed to reconstruct enrollment.

The primary outcome is a participant count, not an event count. If one participant had more than one qualifying serious adverse event, the endpoint would still count that participant once under the stated “one or more” definition. The record does not supply event-level details that would allow the number, timing, or pattern of qualifying events to be examined separately.

What can be said about statistical planning?

A sample-size planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with planning scenarios based on a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. No resulting planning figures or trial-specific sample-size justification are reported in the registry record.

General statistical explanation: power is a design concept describing the chance that a specified analysis will detect a specified effect under assumed conditions. It is not a measure of how persuasive an observed result is after data have been collected. A planning estimate based on an observed effect also should not be mistaken for an independently established effect size. The posted results do not include a comparative effect estimate for the primary binary outcome.

Why do the PK outcomes need separate interpretation?

The registry lists area under the concentration-versus-time curve from zero to infinity and maximum observed concentration in each period as secondary pharmacokinetic outcomes. These measures describe drug concentration over time and the highest observed concentration, respectively. They are distinct from the participant-level serious adverse event count. The numerical PK results and their statistical analyses are not reported in the registry record, so no comparison or interpretation of those measures can be made from the posted primary results.

Overall, the available statistical information supports a descriptive account of the primary outcome by exposure group. Details of a formal model, variance estimates, confidence intervals, hypothesis tests, and adjustments for crossover structure 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("Placebo: Japanese", "Placebo: Caucasian", "2 x Placebo: Japanese", "50 mg Lasmiditan: Japanese", "50 mg Lasmiditan: Caucasian", "100 mg Lasmiditan: Japanese")
n      <- c(10, 8, 2, 6, 8, 7)
events <- c(0, 0, 0, 0, 0, 0)
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  Placebo: Japanese  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Placebo: Caucasian  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  2 x Placebo: Japanese  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  50 mg Lasmiditan: Japanese  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  50 mg Lasmiditan: Caucasian  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  100 mg Lasmiditan: Japanese  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and two secondary pharmacokinetic outcomes: area under the concentration-versus-time curve from zero to infinity and maximum observed concentration of lasmiditan in each period. It does not report a plan for controlling multiplicity across these outcomes, dose groups, or participant groups. Multiplicity refers generally to the added chance of a false-positive finding when several hypotheses are tested; whether and how that issue was addressed is not reported in the registry record.

The primary population is defined as all enrolled participants who received at least one dose of study drug. The record does not provide a more detailed analysis-population definition, such as a separate pharmacokinetic population or rules for including incomplete period data. The disposition of participants with missing endpoint observations is not reported in the registry record, nor are methods for handling missing data.

The record reports no posted analyses for the primary endpoint and indicates that a two-arm comparison is not estimable for this binary outcome. It does not provide a statistical analysis plan, planned hypothesis tests, covariate adjustments, or rules for handling multiple exposure periods. Numerical results for the listed secondary pharmacokinetic outcomes are also not reported in the registry record. These omissions mean that the posted material supports descriptive reading of the recorded counts but does not support reconstruction of a prespecified inferential analysis.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

For the primary endpoint, every listed exposure group has a value of zero for participants with one or more serious adverse events considered related to study drug administration. The timeframe is baseline up to Day 20. This endpoint is based on investigator attribution and is distinct from counts of serious adverse events regardless of causality.

The adverse-event summary also records zero participants affected by a serious adverse event in each listed group. It reports non-serious adverse-event participant counts by exposure group: 6 for Japanese participants receiving placebo, 4 for Caucasian participants receiving 50 mg lasmiditan, 5 for Japanese participants receiving 100 mg lasmiditan, 3 for Caucasian participants receiving 100 mg lasmiditan, 6 for Japanese participants receiving 200 mg lasmiditan, 3 for Caucasian participants receiving 200 mg lasmiditan, 6 for Japanese participants receiving 400 mg lasmiditan, and 5 for Japanese participants receiving 2 x 200 mg lasmiditan. The counts are 0 for Caucasian participants receiving placebo, Japanese participants receiving 2 x placebo, and Japanese participants receiving 50 mg lasmiditan.

These group counts are not independent totals because the design is crossover and participants may contribute across periods. They also do not establish that any non-serious event was caused by study drug. The registry states that adverse-event summaries include events regardless of causality. A zero serious-event count describes what was recorded; it does not demonstrate absence of risk.

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

The posted primary result establishes a narrow descriptive fact: no participant in any listed exposure group was recorded as having a serious adverse event considered by the investigator to be related to study drug administration during baseline up to Day 20. The adverse-event summary likewise reports zero participants affected by a serious adverse event in each listed group. This is the direct scope of the result.

It does not establish that lasmiditan has no serious risks. Zero observed events in a limited study cannot rule out events that were not observed, and the registry provides no uncertainty interval for the primary outcome. Nor does it establish that lasmiditan and placebo are equivalent. The registry does not report a comparative estimate or test for the primary endpoint, and its note says values are missing or not estimable for a two-arm comparison.

The result also should not be generalized beyond the study population and conditions. The participants were healthy Japanese and Caucasian individuals in a Phase 1 study. The posted record does not establish how these findings apply to people with a medical condition, to other populations, or to circumstances outside the studied doses and periods. The primary safety window is explicitly limited to baseline up to Day 20.

The study’s stated aims included pharmacokinetics, but numerical results for the listed concentration measures are not reported in the registry record. Thus, the primary safety counts do not answer how exposure differed between participant groups or dosing periods. They also do not provide a complete account of non-serious event characteristics, since event-level descriptions and relatedness assessments are not available in these posted results.

In practical statistical terms, the findings are descriptive and limited in precision. They should be interpreted alongside the crossover design, the multiple dose-period groups, and the absence of a reported inferential analysis. They do not constitute medical advice or a general conclusion about treatment effects.

14. Why This Trial Matters Statistically

This study illustrates why design details matter when reading a safety count. A crossover study can record participants under multiple dose or placebo exposures, so exposure-group counts are not necessarily counts of separate, non-overlapping groups. Reading them as if they were independent parallel arms, or adding them to recover the number of participants, would misrepresent the design. The registry records enrollment of 27, while the exposure counts vary by group.

It also demonstrates the distinction between a descriptive result and a comparative estimate. The posted primary result consists of zero counts for the defined related serious adverse event outcome. The record does not report a two-arm estimate, confidence interval, or hypothesis test for that endpoint. A count can faithfully describe observed data without answering whether groups differ or how precisely an underlying risk has been estimated.

The endpoint definition is also important: it concerns serious adverse events judged by the investigator to be related to study drug, within a specified timeframe. That is not interchangeable with the broader adverse-event summary, which includes events regardless of causality and separately reports non-serious events. Clear separation of endpoint definition, attribution, and observation window prevents overstatement.

Finally, the registry lists pharmacokinetic outcomes alongside safety outcomes, but the numerical PK findings are not reported in the registry record. This reinforces that a study can have multiple aims while the posted results address only some of them. For biostatistical interpretation, design, estimand, analysis, and reporting must be read together; descriptive counts alone cannot fill gaps in the analysis 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.

This is a small Phase 1 study in healthy Japanese and Caucasian participants. Although enrollment is recorded as 27, the counts represented in the individual exposure groups vary, and crossover participation means they should not be regarded as separate, non-overlapping sets of participants. The record does not give enough detail to reconstruct the number of participants contributing complete data to each period or endpoint.

The primary result is limited to serious adverse events that the investigator considered related to study drug administration, during baseline up to Day 20. It does not provide event-level information, timing, or details about seriousness and clinical course. The registry separately reports non-serious adverse-event counts, but the posted record does not provide a complete event-by-event account in the primary results.

No comparative estimate or uncertainty interval is reported for the primary binary endpoint, and the record indicates that a two-arm comparison is not estimable. The statistical analysis plan, handling of missing observations, crossover-period methods, and multiplicity approach are not reported in the registry record. These omissions limit assessment of how a formal treatment comparison might have been made.

Although pharmacokinetic outcomes are listed, their numerical results are not reported in the registry record. The safety counts therefore cannot address differences in drug exposure. Findings from healthy participants and the listed regimens also cannot, on their own, establish what would occur in other populations or settings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Lasmiditan in Healthy Japanese and Caucasian Participants — NCT03579940.
• Registry record last updated 2019-11-29; status last verified 2018-08.
• Results first posted 2019-11-29.
• 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

The registry describes NCT03579940, a completed Phase 1 randomized, double-blind crossover study of oral lasmiditan and placebo in healthy Japanese and Caucasian participants. Enrollment was 27. The study began on 2018-06-27, and primary completion was recorded as 2018-08-09. Its stated aims were safety, tolerability, and pharmacokinetics.

The primary outcome counted participants with one or more serious adverse events considered related to study drug administration from baseline up to Day 20. The posted count is zero in each listed exposure group. Non-serious adverse-event counts are reported by group, while numerical results for the two listed pharmacokinetic outcomes are not reported in the registry record.

The registry does not report a comparative analysis for the primary binary endpoint, and notes that values are missing or not estimable for a two-arm comparison. Because the design is crossover, exposure-group counts should not be treated as distinct participant groups. The record does not report a detailed analysis plan, missing-data methods, or multiplicity procedures.