A Study of LY3526318 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3526318 in Healthy Participants (NCT03977974), 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’s stated purpose was to learn about the safety and side effects of oral LY3526318 in healthy participants, while also assessing pharmacokinetics and a pilot food effect. This is an early-phase study in a healthy-participant population, not a trial designed to answer a treatment question in a patient population.

Its primary safety outcome is a count of participants, rather than a measure of symptom severity, drug concentration, or treatment benefit. The posted outcomes also include pharmacokinetic measures such as concentration over time, maximum observed concentration, and time to maximum concentration. The record does not report numerical results or analyses for those measures. The central interpretive question is therefore narrow: what do the recorded serious adverse event counts show, and how much comparative inference is possible from the posted results?

3. Trial Design

This was a randomized, double-blind, sequential Phase 1 study of LY3526318 in healthy participants. The registry lists an enrollment of 76 and describes two parts. Each participant enrolled in only one part. Part A was described as lasting up to 28 days and Part B up to 51 days, including screening and follow-up. The record lists the study as terminated; the reason for termination is not reported in the registry record.

Part A included single-ascending-dose groups, with posted results for placebo and LY3526318 doses from 10 mg through 300 mg. The listed groups also include fed or fasted conditions and specific food-effect comparisons. Part B included multiple-ascending-dose groups, with placebo and LY3526318 taken once daily; the posted descriptions state that treatment was given for 14 days. The result arm labels show separate groups, rather than one pooled active-treatment group and one pooled placebo group.

The registry names randomization and double masking, but details of the allocation procedure, masking implementation, and sequence of dose escalation are not reported in the registry record. A formal protocol, stopping rules, and details of how participants moved through the sequential cohorts are also not reported in the registry record. The arm descriptions are not fully detailed in the record, so the posted arm labels are the most reliable guide to the group-level results.

The 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, measured from baseline up to 32 days. The primary outcome population was participants who received at least one dose of study drug. The registry also lists pharmacokinetic secondary outcomes and a pilot food-effect purpose. The study began on 2019-06-21, and the primary completion date is 2020-03-05.

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: This study consists of 2 parts: * Part A: Single-ascending dose (SAD, \[including a food effect (FE)\]). * Part B: Multiple-ascending dose (MAD). Both parts were randomized, double-blind, and placebo-controlled, with the exception of the 100 milligram (mg) FE part.

Only the first 6 of 13 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 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.

Only the first 6 of 14 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 32 Days.

The primary endpoint counts participants who experienced one or more serious adverse events that the investigator considered related to study drug administration. It is a participant-level count: a participant is counted if the qualifying event criterion is met. The registry’s description defines a serious adverse event by outcomes such as death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability, congenital anomaly or birth defect, and other important medical events that may require intervention.

This type of endpoint is used to capture serious safety events during the specified observation period. It focuses on events judged serious and considered related by the investigator; it is not a count of all adverse events, nor does it summarize event severity beyond the serious-event definition. The timeframe is baseline up to 32 days, and the stated analysis population is all participants who received at least one dose of study drug.

The posted primary results show 0.0 participants in every listed arm. That result describes the observed counts for this endpoint in the registry. It does not establish that no other adverse events occurred: the adverse-event module separately lists other, non-serious events. Nor does an observed zero determine the probability of rare events or establish the absence of risk. The group sizes are limited, and the record does not provide an inferential comparison or precision estimate for this endpoint.

The endpoint is distinct from the listed pharmacokinetic outcomes, which concern drug concentration and its timing. It also differs from an endpoint that counts each event, because the primary measure is the number of participants with at least one qualifying event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had at least one qualifying serious adverse event or did not. The registry reports the number of participants meeting that criterion in each arm. This is different from an event-rate analysis that counts repeated events per participant, and different from an analysis of time until an event. The displayed counts do not capture how many qualifying events an individual participant might have had.

What does a zero count say?

A zero is the observed count in the reported group. It does not mean the underlying event probability is known to be zero. In general, sparse binary data make estimates imprecise, particularly when group sizes are limited. A confidence interval can show that uncertainty by giving a range of values compatible with the observations under the chosen statistical method. The registry results do not include confidence intervals for the primary endpoint, so the uncertainty cannot be read directly from a posted interval.

Here, the posted primary counts are 0.0 for every arm. A conventional comparison of event proportions relies on there being enough information in the group counts to estimate a contrast and its uncertainty. When there are no observed events across the compared groups, an ordinary two-arm comparison may not be estimable from summary counts. The registry output flags the two-arm comparison as missing or not estimable. This is why the page does not present a comparative effect estimate or a significance test. A lack of an estimable comparison is not evidence of equivalence.

Why are the arms not one simple comparison?

The study includes multiple dose cohorts, placebo groups, single-dose and multiple-dose parts, and fed or fasted conditions. Those groups address different elements of the study purpose. Combining them into one active-versus-placebo contrast would require a prespecified rationale and a statistical plan; neither is reported in the registry record. The posted arm-specific counts should therefore be read as cohort descriptions, not as a pooled treatment effect.

The primary endpoint population is stated as participants who received at least one dose. This is an exposure-based definition. The registry does not report whether other analysis populations were defined, whether any participants were excluded from the outcome analysis, or how missing outcome information was handled. No assumptions about those procedures can be inferred from the displayed counts.

How should the planning illustrations be read?

The planning illustrations, where available, are not the study’s design justification and are not observed power. In general, such illustrations use assumptions about the effect to detect, the significance level, allocation, and a statistical approximation to show how a hypothetical future study might be planned. They do not tell us the probability that this completed study would find a result, and they cannot repair the lack of an estimable two-arm contrast in the posted data. The registry does not report the trial’s own sample-size justification or power calculation.

For this study, the stated assumptions for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These assumptions describe the illustration, not a reported design decision by the trial investigators. Since the posted primary outcome does not yield an estimable two-arm comparison, an effect-based planning exercise should not be treated as a reliable estimate of a clinically meaningful difference.

What other statistical information is absent?

The registry lists pharmacokinetic measures, including area under the concentration-versus-time curve, maximum observed concentration, and time to maximum concentration. The record reports no analyses for the outcomes, and the posted material does not provide a numerical analysis of those endpoints. Statistical methods for those measures, including any transformation, model, handling of measurements below a quantification limit, or food-effect contrast, are not reported in the registry record.

Likewise, details of interim analyses, dose-escalation decision criteria, model adjustment, and multiplicity control are not reported in the registry record. These details matter because a sequential study with several dose and food-condition groups can involve multiple questions, while the uncertainty for any one estimate depends on the analysis chosen. The posted primary counts remain useful as a transparent descriptive summary, but they do not substitute for a full analysis plan or detailed numerical results.

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("SAD: Placebo", "SAD: 10 mg LY3526318", "SAD: 30 mg LY3526318", "SAD: 50 mg LY3526318", "SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318", "SAD: 200 mg LY3526318 (Fasted) and 200 mg LY352631")
n      <- c(12, 6, 6, 6, 6, 6)
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  SAD: Placebo  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7
ARM  SAD: 10 mg LY3526318  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  SAD: 30 mg LY3526318  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  SAD: 50 mg LY3526318  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  SAD: 200 mg LY3526318 (Fasted) and 200 mg LY352631  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary pharmacokinetic outcomes, including area under the concentration-versus-time curve from zero to infinity, area under the curve from zero to 24 hours, maximum observed concentration, and time to maximum concentration. Some measures appear in more than one listed entry. The record reports seven outcome measures in total and six posted secondary outcomes, but lists no statistical analyses.

When a study addresses multiple outcomes, doses, or food conditions, multiplicity can arise because several statistical questions are considered. In general, multiplicity procedures can control the chance of false-positive findings across a defined family of tests. Whether such a procedure was planned or used is not reported in the registry record. There are no posted p-values or inferential analyses to assess, adjusted or unadjusted.

The primary outcome population is described as participants who received at least one dose of study drug. Beyond that definition, the registry record does not report analysis-population rules or the number of participants contributing outcome data in each analysis. Missing-data methods, reasons for missingness, and any imputation approach are not reported in the registry record. The posted results do not permit assessment of whether missing outcome data could have affected the counts.

The record also does not report interim analyses, a prespecified hierarchy of outcomes, or how the sequential dose cohorts informed later decisions. These omissions limit reconstruction of the statistical strategy. The safest interpretation is to treat the posted event counts as descriptive and not to infer that multiplicity, missing data, or sequential decisions were handled in a particular way.

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

The primary safety result counts participants with one or more serious adverse events that the investigator considered related to study drug administration. The posted count is 0.0 in every listed arm. The adverse-event module also lists 0 participants with serious adverse events in each group and 0 deaths. These are observed counts for the groups and definitions shown in the registry; they are not proof that serious events could not occur.

The adverse-event module separately reports participants with other non-serious adverse events. Those counts vary among groups, with affected participants recorded in some cohorts and no affected participants in others. The tables show the group-level figures; they should be read alongside the group sizes and the particular dose or food condition, rather than as one pooled comparison.

The primary endpoint and the non-serious adverse-event counts answer different questions. The primary endpoint is restricted to serious events judged related by the investigator, whereas the registry states that the adverse-event summaries include serious events and other non-serious events regardless of causality. These figures are descriptive. The registry does not report a statistical comparison of safety outcomes, and the limited cohort sizes mean that the counts alone do not precisely characterize uncommon events.

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

The posted results show that no participant in any listed arm was recorded as having a serious adverse event considered related to study drug administration for the primary outcome timeframe. The adverse-event tables likewise list no serious adverse events or deaths in the displayed groups. Other non-serious adverse events were recorded in some groups. These findings describe what was entered in the registry for this healthy-participant study.

They do not establish that LY3526318 is free of serious adverse effects, that its risks are the same as placebo, or that one dose is safer than another. A zero count in a limited cohort does not rule out an event that might occur less often or under different circumstances. The registry does not provide a confidence interval or an estimable two-arm comparison for the primary outcome, so the precision of any between-group difference cannot be assessed from these results.

The results also do not answer whether the drug is effective for a disease. Participants were healthy, and the stated purposes were safety, tolerability, pharmacokinetics, and a pilot food-effect study. The listed pharmacokinetic outcomes do not have numerical analyses in the posted results, so no conclusion about concentration, exposure, or the effect of food can be drawn from the primary safety counts.

Finally, the registry status is terminated, but the reason for termination is not reported in the registry record. It would be inappropriate to infer a cause from the event counts or from the status alone. The most defensible conclusion is limited to the observed data: no qualifying related serious adverse events were recorded in the listed arms, while comparative safety and less common risks remain uncertain in the absence of an estimable analysis.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary endpoint is simple to describe but difficult to compare when every group has a zero count. Binary outcomes are often summarized as event counts and group sizes. When no events are observed, those counts do not yield an ordinary treatment contrast with useful precision. The distinction between a descriptive result and an inferential result is important: the former says what was observed, while the latter requires an estimate of uncertainty and a defensible comparison.

The design also has multiple cohorts rather than a single pair of groups. The study includes single-dose and multiple-dose parts, several dose levels, and food conditions. That structure is suited to several early-phase questions, but it means a reader cannot treat all active-treatment participants as one group without a justified pooling plan. The registry does not report such a plan or an analysis strategy.

The record makes a further useful distinction between the primary related-serious-event endpoint and the broader adverse-event summaries. The absence of a serious event does not imply the absence of non-serious events, and the relatedness criterion is not the same as reporting events regardless of causality. Reading the endpoint definitions alongside the results avoids overstating what a zero count means.

Finally, the posted statistical record lacks analyses for the listed pharmacokinetic outcomes and does not report a sample-size justification, multiplicity method, or missing-data procedure. This demonstrates why trial registration results should be read as a specific record of posted information, not as a substitute for a protocol and full statistical analysis. The counts are informative as cohort-level descriptions, but the record leaves important questions about precision and comparative interpretation 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 primary endpoint is rare-event focused, and the listed cohorts are limited in size. A lack of observed events therefore cannot establish that the underlying risk is absent or precisely estimate its frequency. The record gives no confidence interval or other uncertainty estimate for the primary result.

The study contains multiple dose and food-condition groups. Because no two-arm comparison is estimable from the posted summary results, the data do not support a reported comparative effect for the primary endpoint. The registry does not report a pooling strategy, a model for comparing cohorts, or a statistical analysis plan that would clarify how the several groups were intended to be evaluated.

Although the registry lists pharmacokinetic secondary outcomes, the record includes no analyses for them. Numerical results for exposure, maximum concentration, and time to maximum concentration are not available in the posted information. The arm descriptions are also not fully detailed, which limits reconstruction of every dosing and food-condition sequence.

The registry does not report the reason for termination, the trial’s sample-size justification, interim-analysis procedures, missing-data methods, or the handling of analysis populations beyond the primary endpoint’s stated population. These are specific gaps in the record, not evidence that the procedures were absent. The findings are also from healthy participants, so the registry results do not directly address outcomes in a patient population. All of these limitations narrow the conclusions that can be drawn from the posted counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY3526318 in Healthy Participants — NCT03977974.
• Registry record last updated 2025-09-12; status last verified 2025-09.
• Results first posted 2025-09-12.
• 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.

19. Record Summary

This randomized, double-blind, sequential Phase 1 study examined oral LY3526318 in healthy participants. It included single-ascending-dose and multiple-ascending-dose parts, placebo groups, and a pilot food-effect component. Enrollment was 76. The registry lists the study status as terminated, with a primary completion date of 2020-03-05; the reason for termination is not reported in the registry record.

The primary endpoint was the number of participants with one or more serious adverse events considered related to study drug administration from baseline up to 32 days. The posted count is 0.0 in every listed arm. The adverse-event module also lists no serious adverse events or deaths in the displayed groups, while reporting other non-serious events in some groups. No two-arm statistical comparison was estimable from the posted primary summary data, and no analyses are listed for the pharmacokinetic secondary outcomes. The results are descriptive and do not establish comparative safety or exclude uncommon events.