A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia (NCT04009577), a randomized phase 3 study. The primary outcome is Percentage of Overall Participants Who Transitioned to LEM at the End of the Titration Period of Core Study.

2. Clinical Question

The clinical question is about whether participants could make a next-dose transition from zolpidem to lemborexant and remain on lemborexant through the end of the 2-week titration period. It is not framed as a comparison of lemborexant with placebo, continued zolpidem, or another insomnia treatment. The listed primary outcome is a participant percentage, rather than a continuous measure of sleep or a time-to-event outcome.

The trial included people who used zolpidem on different schedules. The registry describes Cohort 1 as participants using zolpidem at least 3 but fewer than 5 nights per week during at least 2 weeks of the 3-week screening period. Cohort 2A and Cohort 2B involved use on at least 5 nights per week during at least the last 2 weeks of screening. Cohort 2A initially received lemborexant 5 mg, while Cohort 2B initially received lemborexant 10 mg. The available description does not fully define the distinction between Cohort 1A and Cohort 1B.

In this setting, a transition percentage can describe whether participants met the registry’s continuation criterion after starting lemborexant. It does not, on its own, establish comparative benefit or explain why a participant did or did not continue. The registry record does not report the primary outcome result, so the percentage and its precision cannot be interpreted from the posted information.

3. Trial Design

This was a randomized, open-label, parallel study listed as Phase 3 and described in its official title as a multicenter pilot study. The registry reports enrollment of 53 participants and a completed status. The study began on 2019-07-15, and primary completion was recorded as 2020-03-17. The registry identifies Eisai Inc. as sponsor.

Randomization was reported, but the record does not report the randomization procedure, allocation ratio, or whether allocation was stratified. Masking was listed as none. This means the study was open-label as recorded; the registry does not describe additional steps to conceal treatment assignment from participants, investigators, or outcome assessors. The parallel model indicates that the listed treatment groups were compared as separate groups, rather than through a crossover design.

The study focused on adults with insomnia who had been taking zolpidem tartrate immediate release or extended release. The registry’s study summary describes intermittent or frequent use, followed by lemborexant 5 mg or 10 mg for 2 weeks. The cohort descriptions indicate that initial dose and zolpidem-use pattern were linked to cohort. Cohort 1 involved less frequent use, while Cohort 2A and Cohort 2B involved use on at least 5 nights per week. Cohort 2A initially received lemborexant 5 mg and Cohort 2B initially received lemborexant 10 mg.

The primary outcome was defined for the overall participant group and was assessed at the end of the titration period, up to 2 weeks. The registry also lists secondary outcomes concerning transition within each cohort, dose increases or decreases, and positive medication-effect ratings on Patient Global Impression of Insomnia items. However, it reports no analyses for these outcomes. The primary outcome is marked as having fewer than two arms, so a comparative primary-outcome estimate is not available in the registry record. A detailed protocol, conduct of the randomization, and statistical analysis plan are not reported in the registry record.

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: A total of 99 participants were screened, of which 46 were screen failures and 53 participants were enrolled and randomized into the Core study. Out of 53 randomized and treated participants in the Core Study, 43 participants entered Extension Phase and 41 participants received study drug.

Core Study

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The FAS included participants who received at least 1 dose of lemborexant.

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: The full analysis set (FAS) included participants who received at least 1 dose of lemborexant.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Overall Participants Who Transitioned to LEM at the End of the Titration Period of Core Study, measured over Up to 2 Weeks.

The primary endpoint is the percentage of overall participants who transitioned to lemborexant at the end of the titration period. The registry defines transition as remaining on lemborexant at the end of the 2-week period and either entering the extension phase or choosing not to enter for reasons not related to lemborexant. Listed reasons unrelated to lemborexant include time commitment, study-related travel expenses, or a preference to continue insomnia management with another health care provider.

This definition treats continuation as a practical, binary outcome: participants either meet the stated transition criterion or they do not. As a general statistical point, a binary endpoint can be summarized as a proportion, making it directly interpretable as the share of an analysis population meeting a prespecified condition. That can be useful when the study question concerns whether participants can proceed to a later phase after a treatment transition.

The endpoint combines continued treatment with a decision about entering the extension phase, while allowing some non-entry reasons to count as a successful transition. It therefore reflects the registry’s operational definition, not simply attendance in the extension phase. The definition also makes the reason for not entering relevant to classification. The registry record does not report how such reasons were assessed or adjudicated.

No primary endpoint value, confidence interval, or analysis result is reported in the registry record. Consequently, the endpoint’s observed proportion and the precision with which it was estimated cannot be described. The registry lists a full analysis set of participants who received at least 1 dose of lemborexant, but it does not report the number included in the primary endpoint analysis or how missing endpoint status was handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists a percentage endpoint, which is a binary outcome expressed as the proportion of participants meeting the transition definition. In the study’s terms, the outcome classifies whether a participant remained on lemborexant at the end of the titration period and met the specified extension-phase condition. The registry’s stated full analysis set includes participants who received at least 1 dose of lemborexant. It does not report the denominator used for the primary analysis or a calculated percentage.

What does a proportion estimate mean?

General statistical explanation: A proportion estimates the share of an analysis population with a defined characteristic or outcome. It is determined by the number of participants meeting the definition relative to the number assessed. A clear outcome definition and a clearly stated denominator are necessary for readers to understand what the estimate represents. In this case, the registry provides an operational definition but does not post the numerator, denominator, or endpoint estimate.

A confidence interval is commonly used to describe uncertainty around an estimate. General statistical explanation: An interval reflects that an estimate from a study population may vary across samples, and its width is influenced by the amount of information and the observed pattern of outcomes. A narrow interval indicates greater precision than a wide interval, but neither interval width nor statistical significance alone establishes clinical importance. No confidence interval for the primary endpoint is reported in the registry record.

Does the record give a comparative analysis?

The record lists the study as randomized and parallel, and the treatment groups include lemborexant 5 mg and 10 mg within cohorts. However, the primary outcome is listed as having fewer than two arms, and the record reports zero analyses. Randomization describes an element of the trial design; it does not by itself provide a treatment-effect estimate. A comparative result would require a defined contrast, an analysis population, and reported outcome data. Those results are not reported in the registry record.

As a general statistical explanation, comparing proportions between groups can be done using an absolute difference or another prespecified effect measure. The measure should be paired with uncertainty estimates and interpreted in light of how participants were assigned and how missing outcomes were handled. No such primary comparison is posted for this study. No difference, ratio, or other treatment effect can be reconstructed from the record’s stated enrollment or group descriptions.

What can be inferred from randomization and masking?

Random allocation can reduce systematic differences between treatment groups at the point of assignment, on average, when implemented as planned. It does not guarantee that groups will be identical, especially in a pilot study with limited group sizes. The registry does not report the random sequence method, allocation concealment, or allocation ratio, so those features cannot be assessed. Masking is listed as none. General statistical explanation: In an open-label study, knowledge of treatment assignment may influence participant reporting, care decisions, or outcome assessment, depending on how outcomes are measured. The record does not explain whether outcome assessors were independent or how subjective assessments were administered.

The secondary outcomes include transition by cohort, changes in dose, and positive medication-effect ratings on Patient Global Impression of Insomnia items. The record does not post analyses for these outcomes. Their listing indicates planned outcome topics in the registry, not evidence that results were analyzed or that any particular pattern was observed.

How should planning illustrations be understood?

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe the target effect as a stated fraction of the observed effect. These are illustrations, not the trial’s own design justification and not observed power. The registry does not report a sample-size justification or explain whether these assumptions were used to plan this study. The illustrations should not be mistaken for evidence that the trial was adequately powered for a particular comparison.

As a general statistical explanation, power is a design property calculated under specified assumptions about an effect, variability, allocation, and analysis. It is not a measure of how persuasive a result is after the study has been completed. A post hoc calculation based on an observed result does not repair a missing estimate or resolve uncertainty around it. The registry record does not report interim analyses, a statistical analysis plan, or methods for adjusting analyses for multiple outcomes.

Other relevant methods details are also absent. The registry record does not report how missing endpoint data were handled, whether any sensitivity analyses were conducted, or whether the endpoint definition changed during the study. Without those details and the outcome analysis itself, the posted information supports description of the design, but not reconstruction of an inferential result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes. The secondary outcomes concern transition within each cohort, dose increases among lemborexant 5 mg groups, dose decreases in the lemborexant 10 mg group in Cohort 2, and positive medication-effect ratings on Patient Global Impression of Insomnia items. The record does not report analyses for these outcomes.

When a study evaluates multiple outcomes or multiple comparisons, the chance of obtaining at least one apparently unusual result can increase if each is tested separately without a prespecified strategy. General statistical explanation: Multiplicity methods can control or describe this issue, depending on the scientific aims and analysis plan. The registry record does not report whether multiplicity was addressed, which outcomes were included in any testing hierarchy, or whether the secondary outcomes were intended as descriptive or inferential.

The record defines the full analysis set as participants who received at least 1 dose of lemborexant. It does not report a primary analysis denominator, the number of missing endpoint observations, or how missing observations were classified or analyzed. The endpoint definition allows certain reasons for not entering the extension phase to count as transition, but the record does not describe how reasons were gathered or what happened when a reason could not be determined. These details matter because missing outcome status and endpoint classification can affect a proportion estimate.

The registry also does not report a statistical analysis plan, interim analyses, sensitivity analyses, or a sample-size justification. These items are not necessarily required to appear in every registry entry, but their absence limits assessment of prespecification and robustness. No conclusion about the conduct of analyses should be inferred from the absence of those details alone. For this study, the central limitation is that no primary or secondary outcome analysis is posted in 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (5.9%), acute respiratory failure (5.9%).

The registry reports adverse events by cohort, lemborexant dose, and study phase. In every listed core-study group, the count of participants with a serious adverse event is 0. In the extension phase, the Cohort 2B lemborexant 10 mg group lists 1 participant with a serious adverse event among 17 at risk; the other listed extension groups report 0. The recorded death count is 0 for every listed group.

For other adverse events, the core-study Cohort 2A lemborexant 5 mg group lists 2 participants among 21, and the Cohort 2B lemborexant 10 mg group lists 6 among 22. In the extension phase, the Cohort 2B lemborexant 10 mg group lists 5 among 17; the other listed groups report 0. The registry names pneumonia and acute respiratory failure as serious adverse-event terms, each reported as 5.9%. These terms are not assigned to particular groups in the posted summary.

These are descriptive event counts, not evidence of a causal relationship or a comparative safety difference. Group sizes are limited, and there is no placebo or continued-zolpidem safety group described. The registry does not provide an analysis of exposure-adjusted rates, event timing, severity beyond the serious-event classification, or investigator judgments about causality. The counts should be read in the context of those reporting limits.

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

The study addresses a practical transition question: whether participants who had been taking zolpidem remained on lemborexant through the end of a short titration period and met the registry’s stated continuation criterion. The registry defines this outcome and identifies relevant cohorts and initial doses. It does not report the outcome value, however, so the posted record does not show what percentage met the definition.

The available record therefore does not establish how frequently participants transitioned, how precise any estimate was, or whether transition differed by dose or cohort. It also does not provide a comparative effect against continued zolpidem, placebo, or another insomnia treatment. The randomized design and listed treatment groups should not be mistaken for a reported comparative analysis when the primary outcome is listed as having fewer than two arms and the registry lists zero analyses.

Even if a transition percentage were available, it would describe the endpoint as defined rather than every aspect of treatment experience. The definition combines remaining on lemborexant with either entering an extension phase or not entering for specified reasons unrelated to lemborexant. It does not, by itself, describe symptom change, sleep quality, durability of treatment, or the reasons for discontinuation beyond the listed examples. The registry’s secondary outcomes identify some additional topics, but no results for them are posted.

Safety counts offer a limited descriptive view. They document serious and other adverse events in the listed treatment groups and report no deaths. They cannot establish that events were caused by lemborexant or compare risks with a non-lemborexant treatment. The registry does not report detailed safety analyses or exposure-adjusted results.

Accordingly, the record is informative about the study’s purpose and design but insufficient to determine its primary outcome findings. The absence of posted results should not be interpreted as a positive or negative finding. It means that the transition estimate and its uncertainty are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is a transition proportion rather than a conventional treatment-versus-control contrast. The endpoint asks whether participants remained on lemborexant at the end of the titration period and met a specified continuation condition. Such endpoints can address feasibility and treatment continuation, but they need a transparent definition, a denominator, and an estimate with uncertainty to support interpretation.

The record makes the operational definition visible, including the allowance for not entering the extension phase for reasons unrelated to lemborexant. This matters because a composite continuation rule can classify participants differently from an endpoint that simply counts extension-phase entry. Readers need to know both the rule and the observed outcome to understand what the percentage represents. The definition is present, but the primary result is not.

The trial is also listed as randomized while the primary outcome has fewer than two arms. This distinction is important for statistical reading: design features do not substitute for a reported contrast. Without a posted primary analysis, the randomized structure cannot be used to infer a treatment effect or a dose comparison.

Finally, the registry lists a range of secondary outcomes and safety counts, but does not report analyses for the outcomes. This illustrates why registry descriptions and results are different kinds of evidence. Outcome definitions can help readers understand what investigators intended to measure; only reported results can show what was observed and how uncertain those observations were. The missing primary analysis limits what can be concluded from this record, regardless of the study’s completed status.

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 main limitation for interpreting this trial is the absence of posted outcome analyses. The registry record reports the primary endpoint definition but no primary estimate, confidence interval, or analysis. It lists zero analyses and marks the primary outcome as having fewer than two arms. The record therefore does not support an estimate of transition frequency or a comparison between treatment groups.

The listed enrollment of 53 does not reveal the primary endpoint denominator. The full analysis set is defined as participants who received at least 1 dose of lemborexant, but the record does not report group-specific analysis counts, missing endpoint data, or how missing status was handled. It also does not describe how reasons for not entering the extension phase were collected or classified.

The study was open-label, and the registry does not report whether outcome assessment was blinded or independently reviewed. The randomization method, allocation ratio, and concealment procedures are also not reported in the registry record. These missing details prevent assessment of potential biases in assignment and outcome measurement.

The cohorts differed by zolpidem-use pattern and initial lemborexant dose, which limits straightforward interpretation of any unadjusted differences across groups. The registry does not post an analysis that accounts for these cohort distinctions. The safety data are descriptive, include relatively small listed groups, and have no non-lemborexant comparator. The record does not report a statistical analysis plan, multiplicity approach, interim analyses, or sample-size justification. These limitations concern what can be assessed from the registry record; they do not establish that unreported procedures were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia — NCT04009577.
• Registry record last updated 2021-04-12; status last verified 2020-02.
• Results first posted 2021-04-12.
• 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

NCT04009577 is a completed, randomized, open-label, parallel Phase 3 pilot study sponsored by Eisai Inc. It enrolled 53 participants and evaluated transition from zolpidem to lemborexant in adults with insomnia. The study began on 2019-07-15, with primary completion recorded as 2020-03-17.

The primary endpoint was the percentage of participants meeting the registry’s definition of transition at the end of the titration period, up to 2 weeks. The registry defines the analysis population as participants who received at least 1 dose of lemborexant, but does not report the primary endpoint result or its analysis. The primary outcome is listed as having fewer than two arms, and the record lists zero analyses.

Adverse-event counts are reported by cohort, dose, and phase, with zero deaths in every listed group. The registry does not report the statistical analysis plan, missing-data methods, multiplicity approach, or sample-size justification. The record therefore describes the study question and design but does not provide the primary result needed to estimate transition frequency or its precision.