A Study of LY110140 in Healthy Japanese Male Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY110140 in Healthy Japanese Male Participants (NCT01569126), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period.

2. Clinical Question

This was a Phase 1 study of LY110140 in healthy Japanese male participants, with safety, tolerability, and pharmacokinetics as its stated purposes. The record describes both a single-dose portion and a multiple-dose portion. That distinction matters when interpreting the endpoint: the primary outcome concerns the single-dose period in Cohorts 1, 2, and 3, whereas adverse-event counts are also presented for multiple-dose groups.

For the single-dose portion, participants received one of three LY110140 doses in the fasted state on Day 1. The primary outcome combined two kinds of event criteria: an adverse event considered related to treatment, and any serious adverse event. It was assessed from baseline up to Day 43. The endpoint’s definition does not mean that every adverse event was counted as treatment-related; relatedness was part of only one component of the composite.

The record also describes multiple-dose groups receiving LY110140 or placebo once daily for 28 consecutive days. The stated study purposes included evaluating drug exposure in the bloodstream, and the secondary outcomes listed pharmacokinetic measures for single and multiple doses, as well as corrected QT intervals. Those are different questions from the primary safety endpoint.

The registry record reports an enrollment of 56 and describes randomized allocation, quadruple masking, and a parallel model. It does not report the allocation procedure, the meaning of each masking role, or the detailed sequence by which participants entered the different dose groups. The posted group-level adverse-event counts can therefore be read as descriptive safety information, but the primary composite endpoint cannot be reconstructed from them without a combined result that is not reported in the registry record.

3. Trial Design

The study is registered as NCT01569126, a Phase 1 randomized, quadruple-masked, parallel study sponsored by Eli Lilly and Company. It is marked completed. The registry reports enrollment of 56. The study began in 2012-04, and its primary completion was 2012-09. These record details describe the registered study; they do not, by themselves, establish how participants were assigned or how masking was maintained in practice.

The study included single-dose and multiple-dose portions. In the single-dose portion, three groups received 5 mg, 20 mg, or 40 mg of LY110140 once in the fasted state on Day 1. In the multiple-dose portion, one group received placebo and two groups received 20 mg or 40 mg of LY110140 once daily for 28 consecutive days. The registry describes the participant periods as approximately 6 weeks for the single-dose portion and approximately 10 weeks for the multiple-dose portion.

Randomization is a design approach intended to reduce systematic differences between treatment groups at assignment. Masking is intended to limit the influence of knowledge of treatment assignment on participant experience, clinical care, or assessment. These are general explanations of the design terms. The registry labels the study randomized and quadruple-masked, but a detailed account of randomization methods and which parties were masked is not reported in the registry record.

The primary endpoint was specific to the single-dose period and to randomized participants in Cohorts 1, 2, and 3 who received at least one dose and had at least one postdose safety assessment. Its timeframe was baseline up to Day 43. Multiple-dose adverse-event counts are also posted, but they are not interchangeable with the primary endpoint’s single-dose population and timeframe.

Secondary outcomes included maximum observed drug concentration and several area-under-the-concentration-time-curve measures for single and multiple doses, plus changes from baseline in Bazett’s and Fridericia’s corrected QT intervals. The registry record lists these outcomes but the results described in the available record for this analysis are adverse-event counts. Detailed protocol procedures, visit schedules, the dose-escalation rationale, and the 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: The study consisted of 2 parts: the open-label, single-dose (SD) period which included 3 cohorts (Cohorts 1 to 3) and the placebo-controlled, multiple-dose (MD) period which included 2 cohorts (Cohorts 4 and 5).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

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 randomized participants.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period, measured over Baseline up to Day 43.

The primary endpoint counts participants who had one or more drug-related adverse events or any serious adverse events during the single-dose period. It is a participant-level safety measure: the outcome concerns whether a participant met at least one of the stated event criteria, rather than the total number of event episodes. The registry gives the timeframe as baseline up to Day 43.

The definition of a drug-related adverse event is specific. It had to occur after dosing, or be present before dosing and become more severe after dosing, and be considered related to study treatment. Serious adverse events form a separate part of the endpoint, and the definition includes any serious adverse event, whether or not it was judged related to treatment. This combination is intended to capture both events attributed to treatment and serious events that may warrant attention regardless of attribution.

As a general statistical point, a participant-level binary endpoint can summarize whether an event criterion was met, but it does not describe event severity, duration, recurrence, or the full clinical context. A composite endpoint can also combine components with different meanings; interpretation therefore depends on knowing the component results as well as the combined count.

The registry’s adverse-event group counts separately report participants affected by serious events and by other events. They do not give the combined number of participants meeting the primary endpoint, or identify overlap between its components. The complete primary endpoint result is therefore not reported in the registry record in a form that can be read directly from these separate counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what these results can and cannot establish. The registry reports participant counts in treatment groups. Such counts are direct descriptive summaries: they indicate how many participants were recorded as affected by an event category, alongside the number at risk in that group. They are not, on their own, estimates of comparative treatment effects.

What does a participant count represent?

For an outcome defined as participants with an event, each participant contributes to the count if the event criterion is met. This differs from counting event episodes: one participant may experience more than one episode, while still contributing once to a participant-level measure. The posted adverse-event fields describe affected participants. The registry’s primary endpoint likewise uses a participant-level formulation, namely one or more qualifying events, but the available group summaries separate categories rather than presenting the combined endpoint result.

General statistical explanation: binary outcomes are often described using event counts and denominators, or through an estimated event probability with an uncertainty interval. An interval communicates how much uncertainty remains around an estimate under the chosen method and assumptions. The registry record does not report confidence intervals for the adverse-event counts in this analysis, so none should be inferred from the counts alone.

Why does the endpoint combine event categories?

The primary endpoint includes drug-related adverse events and any serious adverse events. A composite can summarize whether a participant met at least one of several criteria, but its interpretation depends on the components. Here, a non-serious event must be judged related to study treatment to meet the first criterion, while the serious-event criterion is not restricted to events judged related. A participant could potentially meet both criteria, so adding separate component counts would not necessarily yield the number meeting the combined endpoint. The record does not report overlap or the combined count.

What do the design labels contribute?

Random allocation is generally used to support fair comparisons by making assignment independent of participants’ measured and unmeasured characteristics in expectation. Masking is generally intended to reduce the influence of treatment knowledge on behavior or assessment. These design features do not remove uncertainty, and they do not replace clear reporting of outcomes and analyses. The registry identifies the study as randomized and quadruple-masked, but the detailed randomization and masking procedures are not reported in the registry record.

The study is also labeled parallel. In a parallel design, participants are assigned to a group and receive that group’s assigned intervention rather than each participant crossing through all interventions. This is a general explanation of the design term; the record does not provide a fuller account of the operational design. Its listed arms include single-dose LY110140 groups and multiple-dose LY110140 and placebo groups. Because the dose regimens and study portions differ, counts across all groups should not be treated as though they arise from one common exposure condition.

Why is the primary population important?

The endpoint population is defined as randomized participants in Cohorts 1, 2, and 3 who received at least one dose and had at least one postdose safety assessment. This definition describes an exposure-and-assessment-based safety population, rather than simply all enrolled participants. The registry record does not report a full participant flow, exclusions from this population, or missing safety assessments. Therefore, the enrollment figure should not be assumed to be the denominator for the primary endpoint.

For the posted group safety summaries, the denominators are stated separately for each group. The single-dose summaries use groups of 8 participants, while the multiple-dose summaries include groups of 8 or 12 participants. These denominators belong to their respective group summaries; they should not be summed to create a new trial total or used to infer unreported allocation details.

What does a planning illustration mean?

General statistical explanation: a sample-size illustration asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen power and significance level. It is a planning exercise, not a description of what the trial observed and not proof that the trial had adequate power for its outcomes. The registry’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. The registry describes non-time-to-event outputs as participants per arm and time-to-event outputs as total events. These assumptions do not establish that they were used to design or analyze this trial; the trial’s own sample-size justification is not reported in the registry record.

The record does not report a statistical model or inferential comparison for the adverse-event counts. In general, model choice for sparse binary data can matter because small counts may make standard approximations unreliable. Exact methods or other approaches may be considered in some settings, but no method can be attributed to this study from the record. The counts should therefore remain descriptive, without an invented test, interval, or estimate.

Over-dispersion is a general issue for count data when variation is greater than a chosen model expects. It is not directly the issue for these participant-level binary counts, and the registry does not report an over-dispersion analysis. More broadly, the form of the data matters: participant-level binary outcomes, event counts, time-to-event outcomes, pharmacokinetic measures, and corrected-QT changes call for different summaries and analysis methods. The listed secondary outcomes do not have posted results in the information available for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes, including pharmacokinetic measures for single and multiple doses and changes from baseline in Bazett’s and Fridericia’s corrected QT intervals. A study with several outcomes may raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. This is a general statistical issue, not evidence that a particular adjustment was or was not used in this study.

The statistical analysis plan, any hierarchy among outcomes, and any adjustment for multiple testing are not reported in the registry record. The record lists one analysis, but it does not describe an analysis strategy sufficiently to establish how multiplicity was handled. The secondary outcomes should therefore be understood as listed endpoints, not as a set of confirmatory findings.

The record defines the primary safety population as randomized participants in Cohorts 1, 2, and 3 who received at least one dose and had at least one postdose safety assessment. That definition is relevant because it is not identical to simply counting all enrolled participants. A participant without a postdose safety assessment would not satisfy the stated population definition.

Missing-data methods, the extent of missing outcome data, reasons for missingness, and any sensitivity analyses are not reported in the registry record. General statistical explanation: missingness can affect interpretation if participants with unavailable assessments differ systematically from those with observed assessments. Without information about missingness and its handling, the completeness of the endpoint data cannot be assessed.

The registry record also does not report a full participant flow or a detailed account of exclusions and analysis sets. The stated enrollment should not be substituted for outcome-specific denominators, which are reported separately in the adverse-event summaries. No missing-data assumption or imputation method should be inferred.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 fields report 0 affected participants in each listed group. The group denominators are 8 for each single-dose group, 8 for the multiple-dose placebo group, and 12 for each multiple-dose LY110140 group. These are group-level observations over the adverse-event reporting period described in the record; the serious-event risk window specific to each group is not further detailed in the information available for this analysis.

Other adverse events affected 3 participants in the 5 mg single-dose group, 1 in the 20 mg single-dose group, and 2 in the 40 mg single-dose group. In the multiple-dose groups, the corresponding counts were 3 for placebo, 3 for 20 mg LY110140, and 6 for 40 mg LY110140. These counts indicate participants affected, not the total number of events. The record does not provide event-level detail in these group counts, such as severity, duration, recurrence, or attribution for each event.

These categories do not directly reproduce the primary endpoint, which combines drug-related adverse events with any serious adverse events in the single-dose period. The serious-event counts alone do not show whether non-serious events were considered related to treatment or how many participants met either part of the composite. Death counts are not reported in the registry record. The counts are descriptive and should not be read as proof of equivalence or as a definitive comparison between regimens.

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

The record describes a randomized Phase 1 study in healthy Japanese male participants that examined safety, tolerability, and pharmacokinetics for single and multiple doses of LY110140. The posted adverse-event summaries provide participant counts for serious events and other events across the listed dose groups. These summaries allow a limited description of what was recorded in those groups.

For the serious adverse-event category, the posted counts are 0 in every listed group. Other adverse events were reported for participants in both the LY110140 and placebo groups. These observations are not enough to establish that the groups had the same safety profile, or that any one regimen was safer or less safe than another. Small group counts and the absence of inferential analyses limit comparative interpretation.

The primary endpoint is a composite measure for the single-dose period: participants with one or more drug-related adverse events or any serious adverse events. Because the group summaries separate serious events from other events and do not report relatedness or overlap for the composite, they do not provide the primary endpoint’s combined result. The registry record does not report that result in a directly interpretable form.

The record also does not establish how well results apply to people outside the study population. The participants were healthy Japanese males, and the findings should be understood in that context rather than generalized to other populations on the basis of this record alone. The listed secondary pharmacokinetic and corrected-QT outcomes cannot be interpreted from the adverse-event counts, and their results are not reported in the registry record in the information available for this analysis.

In general, a trial’s observed counts describe outcomes within the participants and conditions studied. They do not guarantee what would occur in other settings, nor do they replace uncertainty estimates or a detailed account of outcome ascertainment. The record’s main contribution is descriptive: it documents group-level adverse-event counts and defines a primary safety question, while leaving the combined primary result and several analysis details unreported.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why the endpoint definition and the posted result format must be read together. The primary outcome is a participant-level composite, while the adverse-event summaries distinguish serious events from other events. Those formats answer related but not identical questions. Without a reported combined endpoint count, the primary question cannot be answered simply by quoting the separate categories.

The study also includes different dosing conditions: single-dose groups and multiple-dose groups, including a multiple-dose placebo group. That structure makes it important to preserve the distinctions among regimen, period, and analysis population. A count from a multiple-dose group should not be treated as though it came from the single-dose population used for the primary endpoint.

The registry labels the design randomized, quadruple-masked, and parallel. In general, randomization and masking can help reduce bias in comparisons, but their value for interpretation depends on the details of implementation and complete outcome reporting. Those procedural details are not reported in the registry record. Statistical design labels alone cannot supply the missing endpoint result or describe the uncertainty around the observed counts.

The record is also a reminder that a safety count is not the same as an estimate of comparative risk. Group denominators and affected-participant counts are useful descriptive information, but comparisons require careful attention to uncertainty, endpoint definitions, and the underlying analysis. No confidence intervals or formal tests for these adverse-event counts are reported in the registry record.

Finally, the listed secondary outcomes show that safety and pharmacokinetic questions can coexist in an early-phase trial, while requiring different statistical summaries. The adverse-event counts do not answer the listed questions about drug concentrations or corrected QT intervals. Keeping these outcome types separate helps prevent descriptive safety results from being interpreted as evidence about other outcomes.

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 primary endpoint is not directly reported as a combined participant count in the information available for this analysis. The adverse-event summaries separate serious events from other events, but do not give the number of participants with drug-related non-serious events, the overlap between endpoint components, or the number meeting the composite. This is the most important limitation for interpreting the stated primary question.

The available counts are small group-level summaries. They do not include uncertainty intervals, adjusted comparisons, or a reported inferential analysis. Consequently, differences in counts should not be treated as established differences between groups. The registry record also does not provide event-level descriptions sufficient to assess severity, recurrence, timing, or attribution for the other adverse events.

The primary endpoint applies to a defined single-dose population, while the adverse-event summaries also cover multiple-dose groups. The record does not provide a full participant flow or detailed explanation of how the group summaries map to the endpoint population. Enrollment should not be assumed to equal the analysis population, and group denominators should be interpreted only as stated for their respective summaries.

The registry record does not report missing-data methods, a statistical analysis plan, a sample-size justification for the trial, multiplicity handling, or detailed randomization and masking procedures. It also does not report the results of the listed pharmacokinetic or corrected-QT secondary outcomes in the information available for this analysis. These omissions constrain assessment of analysis choices, completeness, and the broader results.

Generalizability is also limited by the stated study population: healthy Japanese male participants. The registry record does not establish how findings would apply to other populations or settings. These limitations do not negate the value of the recorded descriptive counts, but they define the questions those counts can answer.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of LY110140 in Healthy Japanese Male Participants — NCT01569126.
• Registry record last updated 2014-02-10; status last verified 2014-01.
• Results first posted 2013-11-25.
• 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

NCT01569126 is a completed, randomized, quadruple-masked, parallel Phase 1 study sponsored by Eli Lilly and Company. The registry reports enrollment of 56, with a start date of 2012-04 and primary completion in 2012-09. It studied LY110140 in healthy Japanese male participants using single-dose and multiple-dose regimens, with placebo in the multiple-dose portion.

The primary endpoint counted participants with one or more drug-related adverse events or any serious adverse events during the single-dose period, from baseline up to Day 43. The posted adverse-event summaries report no participants affected by serious adverse events in any listed group and give separate counts for other adverse events. They do not report the combined primary endpoint result. Statistical analysis details, missing-data methods, and results for the listed secondary pharmacokinetic and corrected-QT outcomes are not reported in the registry record in the information available for this analysis.