A Study of Lasmiditan in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Lasmiditan in Healthy Participants (NCT03182920), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, crossover Phase 1 study in healthy participants. The registry describes two groups: an elderly group and a young group. The elderly group had two dosing periods, one with 200 mg lasmiditan and one with placebo. The young group received 200 mg lasmiditan on Day 1. The record does not describe the sequence assigned to the elderly group, the washout interval between periods, or the precise randomization procedure.

Enrollment was 35. The registry reports 18 participants in the elderly lasmiditan group and 17 in the young lasmiditan group for the primary endpoint. For adverse-event reporting, the elderly placebo group and elderly lasmiditan group each have 18 participants at risk, while the young lasmiditan group has 17. These are group-specific registry counts; they should not be added to infer a count of distinct participants in a crossover study.

The study began on 2017-06-16, had primary completion on 2017-08-14, and is listed as completed. The record describes a study lasting up to approximately 19 days, excluding screening. It also describes clinic stays, screening within 28 days prior to Day 1, and a follow-up seven days after the last dose. The detailed schedule of dosing and visits beyond the listed pharmacokinetic sampling times is not reported in the registry record.

The design combines a within-participant treatment comparison in the elderly group with an age-group comparison among participants receiving lasmiditan. Those are different comparisons. The primary endpoint analysis reported by the registry is the comparison of lasmiditan geometric least squares means between the elderly and young groups; it is not a placebo-controlled estimate of an age 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.

Period 1

Washout Period

Period 2

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

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan, measured over Day 1:Predose,0.5, 1, 1.5,2, 2.5, 3, 4,6, 8, 12 hours; Day 2: 24,36 hours; Day 3:48 hours.

The primary endpoint is the maximum observed drug concentration, or Cmax, of lasmiditan, measured in nanograms per millilitre. It captures the highest concentration observed in blood among the scheduled pharmacokinetic samples. The registry lists sampling from predose through 48 hours, including Day 1 samples through 12 hours and later samples on Day 2 and Day 3.

Cmax is used in pharmacokinetic research to describe peak systemic drug exposure. Comparing this measure between the elderly and young groups can help characterize whether the observed peak concentration differs by age group under the study conditions. It is one part of a pharmacokinetic profile; it does not by itself describe the full concentration-time course, the time at which the peak occurred, or how quickly concentrations declined.

The registry reports geometric means and geometric coefficients of variation for the treatment groups. Geometric summaries are often used for concentration data because such measurements can be skewed, with some values much larger than others. The coefficient of variation describes relative spread around the geometric mean. The primary endpoint population is defined as all participants who received at least one dose of study drug.

Cmax is a drug-concentration outcome, not a direct measure of symptom relief or clinical benefit. The record’s study purpose also included tolerability and collection of side-effect information, but those are separate from the primary pharmacokinetic endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a ratio of geometric least squares means for the primary comparison. It does not identify the statistical model, covariates, treatment of period or sequence, or method used to calculate the confidence interval. Those details are not reported in the registry record, so the posted estimate can be described but not fully reconstructed from the record.

What does a geometric mean describe?

A geometric mean is a way of summarizing positive measurements that may be skewed. In general, it is based on transforming values to a logarithmic scale, averaging on that scale, and transforming back. This can make a central summary less dominated by unusually high observations than an arithmetic mean. The reported geometric means for the elderly and young lasmiditan groups are 368 ng/mL and 304 ng/mL, respectively.

The registry also reports geometric coefficients of variation of 43% and 40% for those groups. In general, a coefficient of variation expresses spread relative to a mean, rather than spread in the original measurement units. A geometric coefficient of variation is suited to summaries on a multiplicative scale. It describes variability, but it is not a confidence interval for the group mean and does not show the full range of participant values.

Why report a ratio?

A ratio of geometric least squares means compares model-based group summaries on a multiplicative scale. Least squares means are generally estimates from a statistical model, which may account for features of the design or other terms. The registry does not report the model specification for this analysis, so it is not possible to identify which adjustments were made. The reported ratio is 1.21, and its 90% confidence interval is 0.962 to 1.52.

For a ratio, the equality reference is the point at which the two group summaries are the same. The reported interval extends across that reference. In general, a confidence interval describes values that are reasonably compatible with the data and the assumptions of the analysis; it does not provide the probability that a fixed true value lies inside the interval. Here, the interval leaves substantial uncertainty about the magnitude of the group contrast. No p-value is reported for this analysis.

Why does the study design matter?

A crossover design gives participants more than one treatment condition, which can allow within-participant comparisons. The elderly group had lasmiditan and placebo dosing periods. However, the primary reported comparison is between the elderly and young groups receiving lasmiditan. The registry does not report whether the primary model incorporated crossover-period information, how the treatment sequence was handled, or whether any carryover considerations were addressed. The young group’s listed regimen is a single lasmiditan dose on Day 1.

General statistical interpretation of crossover studies depends on how repeated observations and period effects are handled. A within-participant treatment contrast and a between-group age contrast are not interchangeable. The registry’s reported ratio is an age-group contrast for Cmax; it should not be described as a placebo comparison.

What can planning calculations tell readers?

Sample-size illustrations based on an observed effect are planning exercises, not observed power. In general, such illustrations show how a future study’s required number of participants might vary under stated assumptions about the effect to detect, significance level, allocation, and statistical approximation. The record describes an illustration based on the observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation. It specifies that the target effect is a stated fraction of the observed effect. These assumptions do not establish that the original study was planned that way, and the registry does not report the trial’s own sample-size justification.

Planning values should not be read as evidence that this completed study had a particular probability of detecting its effect. That probability, often called power, depends on the design assumptions and the true effect, which is unknown. The record does not report the original sample-size calculation or a statistical plan for the trial. No additional inference about planned power or interim monitoring is warranted from the posted summary.

How should uncertainty and variability be kept separate?

The coefficients of variation describe variability in concentrations among observations under the reporting scale. The confidence interval describes uncertainty about the estimated group ratio. Greater participant-level variability can make a group comparison less precise, but the coefficient of variation is not itself a measure of uncertainty in the ratio. A confidence interval also depends on the analysis model and data structure, details that are not reported in the registry record.

10. Analyses Reported by the Sponsor

The sponsor’s reported analysis gives a ratio of geometric least squares means of 1.21, with a 90% confidence interval from 0.962 to 1.52. This is the registry’s model-based comparison of the lasmiditan Cmax results in the elderly and young groups. The record does not report a p-value or the model specification.

The group summaries are geometric means of 368 ng/mL for the elderly group and 304 ng/mL for the young group, with geometric coefficients of variation of 43% and 40%. These summaries offer context for the reported comparison, but they are not a replacement for the sponsor’s ratio estimate. The registry does not provide sufficient analysis detail to reproduce the sponsor’s model-based ratio from those summaries alone.

No separate recalculated comparative estimate is stated in the registry record. Accordingly, the sponsor’s estimate and confidence interval are the reported inferential result. The confidence interval includes the equality value, and its range leaves uncertainty about the size of the contrast. No conclusion of equivalence follows because an equivalence margin is not reported.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, but it reports no secondary outcome results. It identifies the primary outcome as maximum observed lasmiditan concentration. For another endpoint, values are missing or not estimable for a two-arm comparison. The registry does not report the name and numerical results for a secondary endpoint comparison in the posted outcome information.

When a study considers multiple outcomes or analyses, the chance of a false-positive finding can increase if many results are tested without accounting for multiplicity. In general, methods such as a prespecified hierarchy or adjustment can address that issue. The statistical plan, any multiplicity procedure, and the intended family of comparisons are not reported in the registry record. The record therefore does not establish whether or how multiplicity was controlled.

The primary endpoint analysis population is all participants who received at least one dose of study drug. The registry does not provide a participant-level accounting of exclusions from the analysis, missing concentration measurements, or reasons for missing data. It does not report an imputation method, a sensitivity analysis, or how incomplete sampling was handled. These details matter because missing pharmacokinetic measurements can affect which observations contribute to a maximum concentration and to a group comparison.

The posted analysis should therefore be read as the reported result for the stated population, with important analysis details unavailable. The record does not report interim analyses, stopping rules, or a full prespecified statistical analysis plan. Those omissions prevent a detailed assessment of outcome selection and missing-data handling, but they do not alter the numerical result that the registry reports.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event listings report zero affected participants in the elderly placebo group, the elderly lasmiditan group, and the young lasmiditan group. Deaths are listed as zero in each group. No serious adverse event terms are listed in the registry’s serious-event summary.

For other adverse events, the record reports 3 affected participants among 18 at risk in the elderly placebo group, 8 among 18 at risk in the elderly lasmiditan group, and 8 among 17 at risk in the young lasmiditan group. These are group-specific counts, not a basis for adding participants across the elderly crossover conditions. The record does not provide event terms or further details in the registry record for this summary.

Zero recorded serious events in these groups does not show that serious events cannot occur. A small, short study in healthy participants cannot characterize uncommon risks with precision. The adverse-event counts also do not by themselves establish a causal treatment difference. They should be read as descriptive observations during this study, alongside the registry’s stated follow-up and study duration, rather than as a complete safety assessment.

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

The result describes a pharmacokinetic comparison in healthy elderly and young participants who received 200 mg lasmiditan. The primary measure was maximum observed concentration. The registry reports group geometric means and a sponsor-estimated ratio with a confidence interval, providing both a central summary and an indication of uncertainty about the age-group comparison.

The confidence interval spans the equality value, so the posted result does not sharply distinguish equality from a difference in the ratio. It does not prove that the groups have identical concentrations, and it does not establish that one group’s peak concentration is definitively higher. The registry gives no equivalence margin, so the result cannot support a formal equivalence conclusion. It also does not report a p-value for this comparison.

These findings are specific to the study’s healthy-participant groups, dose, and sampling schedule. Cmax describes a peak concentration, not the full pharmacokinetic profile. The comparison does not directly answer questions about symptom outcomes, clinical effectiveness, or treatment decisions. The study’s stated purpose was research into pharmacokinetics, safety, and tolerability, not treatment of a medical condition.

The adverse-event listings are descriptive and do not establish the absence of risk. Zero serious adverse events were recorded in the reported groups, while other adverse events were recorded in each group. The limited study size and duration constrain what can be learned about uncommon or delayed events. The registry does not report enough detail about event types or statistical comparisons to support a broader safety conclusion.

Overall, the record offers a bounded estimate of peak drug concentration by age group, accompanied by uncertainty that remains meaningful. It should not be extended beyond this population and endpoint, or treated as a general claim about lasmiditan’s clinical effects.

14. Why This Trial Matters Statistically

This study illustrates how pharmacokinetic outcomes can be summarized and compared when the measurements are concentrations rather than clinical events. A geometric mean and geometric coefficient of variation describe the scale and relative spread of concentration measurements. A ratio of geometric least squares means expresses a group contrast on a multiplicative scale, while its confidence interval communicates uncertainty around that contrast.

It also highlights that a study design can contain more than one kind of comparison. The elderly group had both lasmiditan and placebo dosing periods, whereas the young group received lasmiditan. The primary reported comparison is between age groups after lasmiditan, not between active drug and placebo. Keeping those comparisons separate is essential when interpreting crossover studies and registry results.

The confidence interval is important because the point estimate alone can suggest more certainty than the data support. Here, the reported interval extends across the equality value and covers a range of possible ratios. That uncertainty is relevant even though the point estimate is above equality. The registry’s lack of model details also shows why a published numerical estimate may not be reproducible from group summaries alone.

Finally, the study demonstrates the limits of small, focused pharmacokinetic trials. A peak-concentration endpoint can inform characterization of drug exposure, but it does not substitute for clinical outcomes or comprehensive safety evidence. Registry reporting of sample definitions, analysis methods, missing data, and secondary outcomes helps readers judge which conclusions are supported and which remain unanswered.

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 registry does not report age ranges for the elderly and young categories, so the population contrast cannot be translated into a specific age threshold. The detailed sequence of elderly-group dosing periods, washout interval, and handling of period or sequence effects are also not reported. These details are relevant to understanding a crossover design and its analysis.

The sponsor’s model specification, covariates, and method for constructing the confidence interval are not reported. The record therefore does not permit full reproduction of the ratio estimate from the listed group summaries. It also does not report a p-value, an equivalence margin, a multiplicity strategy, the original sample-size justification, or a complete statistical analysis plan.

For the primary endpoint, the registry defines the analysis population as participants who received at least one dose, but does not explain missing concentration observations, exclusions, or sensitivity analyses. It lists another endpoint for which values are missing or not estimable for a two-arm comparison, and reports no secondary outcome results. This limits assessment of how complete the outcome reporting is.

The study focused on healthy participants and a single 200 mg dose for the groups in the primary comparison. The record describes a study lasting up to approximately 19 days, excluding screening, and a follow-up seven days after the last dose. Such a study cannot characterize longer-term outcomes or provide precise information about uncommon safety events. The posted adverse-event counts are not accompanied by event terms for the non-serious events in the available record. These limitations confine interpretation to the measured pharmacokinetic endpoint and the short-term observations reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Lasmiditan in Healthy Participants — NCT03182920.
• Registry record last updated 2020-01-07; status last verified 2017-10.
• Results first posted 2019-12-06.
• 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

NCT03182920 is a completed randomized, double-blind, crossover Phase 1 study of lasmiditan in healthy elderly and young participants. Enrollment was 35. The primary endpoint was maximum observed lasmiditan concentration, measured in ng/mL, after a 200 mg dose.

The registry reports geometric mean Cmax values of 368 ng/mL for the elderly group and 304 ng/mL for the young group. The sponsor’s ratio of geometric least squares means is 1.21, with a 90% confidence interval from 0.962 to 1.52. The interval spans the equality value, and the registry does not report a p-value or equivalence margin.

Serious adverse events and deaths are listed as zero in each reported group. Other adverse events are reported descriptively. Details of the statistical model, missing-data handling, multiplicity procedures, and secondary outcome results are not reported in the registry record.