A Study of LY3493269 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3493269 in Healthy Participants (NCT04682106), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs).

2. Clinical Question

The study’s stated purpose was to evaluate the safety and tolerability of LY3493269 in healthy participants and to assess its pharmacokinetics. The registry lists two pharmacokinetic secondary outcomes: area under the concentration-versus-time curve from time zero to 24 hours, and maximum concentration. Numerical results for those outcomes are not reported in the registry record. The primary outcome therefore addresses a specific observed safety count, while the broader questions about tolerability and drug exposure require information beyond the posted primary counts.

3. Trial Design

The registry classifies this as a phase 1, randomized, double-masked, parallel study. The study title describes a multiple-ascending-dose investigation of safety, tolerability, and pharmacokinetics in healthy participants. The record lists enrollment of 40. In the primary outcome results, the placebo arm and each of the four LY3493269 plus SNAC arms have 8 participants.

Participants in the placebo group received placebo orally once daily for three consecutive days. The active regimens paired LY3493269 with SNAC and were also given orally once daily for three consecutive days. The posted primary outcome is based on participants who received at least one dose of study drug, with the observation period specified as baseline through Day 44. The registry summary says the study could last up to approximately 71 days for each participant, including screening. That overall duration and the primary outcome’s Day 44 timeframe describe different aspects of the study; the registry does not give more detail about how each visit or assessment was scheduled.

Randomization and masking are design features intended to support fair comparisons and reduce the influence of expectations on treatment assignment or assessment. The record does not report the randomization method, the people or procedures covered by masking, or whether masking was assessed. It also does not report a detailed sequence for dose escalation, allocation within dose groups, or the rationale for selecting the regimens. Those details should not be inferred from the trial title or arm descriptions.

The registry lists three outcome measures overall, including the primary TEAE count and two pharmacokinetic outcomes. It records no statistical analyses for these outcomes. Consequently, the arm-level results can be described as counts, but the registry record does not establish that a formal hypothesis test, an adjusted model, or a planned comparison was carried out.

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.

Overall Study

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs), measured over Baseline through Day 44.

The primary endpoint counts participants who experienced one or more treatment-emergent adverse events from baseline through Day 44. A participant is counted when at least one qualifying event occurs; the endpoint is not a count of every event or a measure of event severity. The definition includes an event that newly emerges during the defined treatment period or an event that worsens relative to the pretreatment state. The registry specifies that a qualifying TEAE does not necessarily have a causal relationship with study treatment.

This type of endpoint is used in an early-phase study to describe the number of treated participants with an event during the specified observation period. It is a broad safety measure: it can register occurrences regardless of whether investigators consider them related to the study drug. That makes it useful for characterizing events observed during treatment, but the count alone cannot determine causation, clinical importance, timing, duration, or severity. Those questions require more detailed event-level information and clinical interpretation.

The posted counts are 4 of 8 participants for placebo, 8 of 8 for 8 mg LY3493269 plus 600 mg SNAC, 8 of 8 for 24 mg LY3493269 plus 600 mg SNAC, 7 of 8 for 12 mg LY3493269 plus 300 mg SNAC, and 6 of 8 for 4 mg LY3493269 plus 300 mg SNAC. These are arm-level participant counts for the primary endpoint. They do not, by themselves, quantify the number of events or identify which events were considered related to treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this?

The primary outcome is binary at the participant level: each participant is classified according to whether one or more TEAEs occurred during baseline through Day 44. The registry reports the number meeting that criterion in each arm and the number of participants in the arm. This is a count outcome, not a continuous measurement such as a laboratory value. It also differs from an event-frequency outcome, because multiple events in one participant still contribute only one participant to the primary endpoint count.

In general, a binary outcome can be summarized using counts and proportions, and comparisons can be expressed as an absolute difference or a relative measure. Those are general statistical options; the record does not report such comparative estimates for this endpoint. No additional effect estimate should be inferred from the counts alone. In particular, no percentage or risk ratio is reported in the registry record.

Why are the arm counts descriptive?

Randomization makes a treatment comparison possible in principle, but a valid interpretation still depends on the analysis plan, the comparison being estimated, and the data available for analysis. Here, the record lists arm-level outcome counts but records no analyses. It also indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. This means the posted record supports description of the observed counts, not an inference from a reported statistical test.

In general, uncertainty intervals help show the range of effects compatible with observed data and a chosen model. A p-value, when used, addresses compatibility with a specified null hypothesis under that model; it does not measure the size or clinical importance of an effect. Neither a p-value nor a confidence interval for a treatment comparison is reported in the registry record. The arm counts should not be presented as though such inferential results were available.

What do the planning illustrations represent?

The registry’s planning illustration uses the observed effect as a starting point, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers effects defined as a stated fraction of the observed effect. The resulting sample-size figures are planning illustrations, not observed trial results and not evidence of the study’s original design. The registry record does not report a sample-size justification for the trial itself, so the illustration should not be used to infer the study’s planned enrollment rationale.

In general, a sample-size calculation describes the number of participants needed under stated assumptions to target a specified operating characteristic. The estimate depends on the assumed effect, outcome variability, significance level, allocation, and method. A calculation based on an effect observed in a small study can be unstable. The registry explicitly characterizes these calculations as planning illustrations; they are not observed power and do not determine whether the trial was adequately powered for its original aims. No planning values need to be interpreted as actual enrollment or as results.

Why can over-dispersion matter?

General statistical note: over-dispersion occurs when observed variability is greater than a model assumes. For count outcomes, an overly restrictive model can understate uncertainty and make comparisons appear more precise than warranted. The primary endpoint is a participant-level binary count, rather than a total event count, and no model for over-dispersion is reported. If event-level counts were analyzed, the number of events per participant could require separate consideration; that is not the posted primary analysis.

What is known about multiplicity and missingness?

The record lists two secondary pharmacokinetic outcomes in addition to the primary safety outcome, but it does not report a multiplicity adjustment or a hierarchy for testing outcomes. In general, testing multiple hypotheses can increase the chance of at least one apparently positive finding if no adjustment or prespecified strategy is used. That general issue cannot be resolved for this trial from the available analysis record.

The primary population is described as all participants who received at least one dose. The registry does not report a method for handling missing endpoint data, withdrawals, or incomplete follow-up. Nor does it report imputation, sensitivity analyses, or a missing-data summary for the primary endpoint. Without those details, the extent to which missingness could affect the reported counts is not reported in the registry record.

The record does not report model covariates, a formal statistical analysis plan, or interim analyses. These methods should not be inferred from the randomized, double-masked design. The correct reading is therefore deliberately narrow: the registry posts counts for the defined endpoint and population, but does not report an inferential analysis or enough detail to reconstruct one.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo", "8 mg LY3493269 + 600 mg SNAC", "24 mg LY3493269 + 600 mg SNAC", "12 mg LY3493269 + 300 mg SNAC", "4 mg LY3493269 + 300 mg SNAC")
n      <- c(8, 8, 8, 8, 8)
events <- c(4, 8, 8, 7, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  8 mg LY3493269 + 600 mg SNAC  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  24 mg LY3493269 + 600 mg SNAC  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  12 mg LY3493269 + 300 mg SNAC  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  4 mg LY3493269 + 300 mg SNAC  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two secondary outcomes: area under the concentration-versus-time curve from time zero to 24 hours and maximum concentration of LY3493269. The record lists three outcome measures overall, but the numerical results for those pharmacokinetic outcomes are not reported in the registry record. It also records no statistical analyses. The primary safety counts are therefore not accompanied by a reported family of tests or a stated testing hierarchy.

Multiplicity is a general concern when several hypotheses are tested. Without a prespecified strategy, repeated testing can increase the probability of observing a nominally unusual result by chance. The registry does not report whether multiplicity was considered, whether adjustment was planned, or whether any secondary outcome was intended to be confirmatory. No conclusion about multiplicity control can be drawn from the outcome list alone.

The primary outcome population is described as participants who received at least one dose of study drug. The record does not report how missing or incomplete TEAE information was handled, whether participants who withdrew were included through their available follow-up, or whether sensitivity analyses were conducted. A missing-data summary for this endpoint is also not reported in the registry record. These omissions limit assessment of how the posted counts relate to all participants who entered the study.

The registry does not report interim analyses, a detailed statistical analysis plan, or a method for handling missing pharmacokinetic measurements. Those details are not inferable from the randomization or masking descriptions. The posted arm-level counts remain interpretable as registry-reported observations, but they cannot substitute for a full account of the analysis population and missing-data procedures.

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 registry reports zero participants with serious adverse events in each listed group. Each group has 8 participants at risk, and the record reports zero deaths in every group. No serious adverse event terms are listed. These are the posted serious-event figures, and they should be read as counts of affected participants rather than as a statement that no serious event could occur.

For general interpretation, observing no serious events in a small group does not establish that the underlying risk is zero. The data are compatible with limited information about uncommon outcomes, and the observation period also matters. The registry reports the primary TEAE timeframe as baseline through Day 44; a separate, more detailed serious-event timeframe is not reported in the registry record.

The registry’s adverse-event description says that serious adverse events, TEAEs, and other non-serious adverse events were reported regardless of causality. A serious event count is not interchangeable with the primary endpoint count: the primary endpoint includes one or more TEAEs, which may be non-serious and need not be considered related to treatment. The serious-event figures alone do not describe the type, severity, timing, or attribution of non-serious events.

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

The posted data establish that the registry records participant counts for one or more TEAEs during baseline through Day 44. The counts vary across the five listed arms: placebo has 4 of 8 participants, the 8 mg LY3493269 plus 600 mg SNAC arm has 8 of 8, the 24 mg LY3493269 plus 600 mg SNAC arm has 8 of 8, the 12 mg LY3493269 plus 300 mg SNAC arm has 7 of 8, and the 4 mg LY3493269 plus 300 mg SNAC arm has 6 of 8. The registry also reports zero participants with serious adverse events and zero deaths in each arm.

These observations do not establish that treatment caused the reported TEAEs. The endpoint definition explicitly includes events that do not necessarily have a causal relationship with treatment. The counts also do not describe the number of events per participant, seriousness of each non-serious event, event duration, or clinical consequences. No event-level summary is included in the primary outcome counts.

The counts do not establish a statistically significant difference between any active regimen and placebo. The registry record does not report inferential comparisons, confidence intervals, or p-values, and it notes that values are missing or not estimable for a two-arm comparison. A reader should not interpret the numerical ordering of these counts as a confirmed treatment effect or a dose-response relationship.

The record’s stated goals also included pharmacokinetic assessment. Although it lists area under the concentration-versus-time curve from time zero to 24 hours and maximum concentration as secondary outcomes, their numerical results are not reported in the registry record. The primary safety endpoint cannot answer those exposure questions.

In general, conclusions from an early-phase study in healthy participants are specific to the studied population, regimens, and observation period. The record does not establish how these results apply to people with a health condition, longer use, or different dosing. The appropriate meaning is therefore descriptive: the registry reports the observed safety counts, while causal, comparative, and broader clinical conclusions remain unestablished by these posted data.

14. Why This Trial Matters Statistically

This trial illustrates why early-phase safety results should be separated into observed counts and statistical comparisons. The primary endpoint is straightforward to describe: it records whether a participant experienced at least one TEAE in the defined period. The posted counts allow readers to see what was recorded in each arm, while the absence of an inferential analysis means that comparative claims cannot be supported by reported tests or intervals.

The design also highlights the difference between a trial’s stated aims and the results available in a registry record. Safety, tolerability, and pharmacokinetics are named aims, and two pharmacokinetic outcomes are listed. Yet the numerical results available for interpretation are the primary safety counts. A complete account of the study’s objectives would need the corresponding outcome results and analysis details, which are not reported in the registry record.

For biostatisticians and clinical researchers, the small arm-level groups underscore the importance of precision. General statistical principles tell us that estimates from small groups can be uncertain, especially for binary outcomes. Counts alone do not show the range of plausible comparative effects. This is one reason to distinguish descriptive summaries from inferential evidence and to avoid treating visible numerical differences as proof.

The record also makes clear that a planning illustration is not the same as the trial’s original sample-size justification. Calculations based on an observed effect and specified assumptions can help explore future planning, but they are not observed power and do not explain the original design unless the registry reports that rationale. Keeping those uses separate prevents retrospective calculations from being mistaken for prespecified methods.

Finally, the serious adverse event figures demonstrate a common interpretive issue: no recorded events in a small group should not be translated into certainty about rare harms. Reading event counts alongside the population, timeframe, endpoint definition, and analysis limitations is essential to a calibrated interpretation.

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 arm-level primary endpoint groups are small, with 8 participants listed in each arm. As a result, each participant represents a substantial part of an arm’s observed count. This limits precision and makes the descriptive counts sensitive to individual outcomes. The registry does not report confidence intervals or other uncertainty estimates for these counts.

The endpoint is broad: it counts any participant with one or more TEAEs, regardless of whether the event was caused by treatment. The primary outcome count does not reveal the types of events, their severity, their timing, whether they recurred, or whether they led to a change in treatment. Although the registry says that adverse events were reported in its Adverse Events section, the primary outcome itself does not provide that detail.

The primary observation period is baseline through Day 44, while the study summary describes a duration of up to approximately 71 days for each participant including screening. The record does not explain the relationship between those time spans in detail. The results therefore should be interpreted within the stated endpoint timeframe, not as a complete account of every possible event over any longer follow-up.

The registry does not report a detailed analysis plan, a method for missing data, interim analyses, or formal comparisons. It also does not report numerical pharmacokinetic results for the listed secondary outcomes. The absence of those details restricts assessment of the intended estimand, the robustness of any comparison, and the relationship between safety and exposure.

Finally, the study concerns healthy participants and specific short-course oral regimens of LY3493269 with SNAC or placebo. The record does not establish how the findings generalize to other populations, treatment durations, or regimens. These limitations define the scope of interpretation; they do not alter the counts recorded for the stated endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY3493269 in Healthy Participants — NCT04682106.
• Registry record last updated 2025-01-14; status last verified 2024-12.
• Results first posted 2025-01-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed, randomized, double-masked, parallel phase 1 study of LY3493269 in healthy participants. It lists enrollment of 40 and five arms: placebo and four LY3493269 plus SNAC regimens, each administered orally once daily for three consecutive days.

The primary outcome is the number of participants with one or more TEAEs from baseline through Day 44 among participants who received at least one dose. The posted counts are 4 of 8 for placebo, 8 of 8 for 8 mg LY3493269 plus 600 mg SNAC, 8 of 8 for 24 mg LY3493269 plus 600 mg SNAC, 7 of 8 for 12 mg LY3493269 plus 300 mg SNAC, and 6 of 8 for 4 mg LY3493269 plus 300 mg SNAC. Serious adverse events and deaths are reported as zero in each arm.

The record lists two pharmacokinetic secondary outcomes, but their numerical results and inferential comparisons are not reported in the registry record. It records no statistical analyses and does not report detailed methods for missing data, multiplicity, or the trial’s sample-size rationale. The available primary results are descriptive arm-level counts.