A Study of LY3303560 in Healthy Participants and Participants With Alzheimer's Disease (AD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3303560 in Healthy Participants and Participants With Alzheimer's Disease (AD) (NCT02754830), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Serious Adverse Event(s) (SAEs) to be Related to Study Drug Administration.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, double-blind, parallel-group study of LY3303560. The registry describes a single-dose, dose-escalation study intended to evaluate safety, tolerability, and pharmacokinetics in healthy participants and participants with Alzheimer’s disease. The study is marked completed, with enrollment of 72. Its recorded start date is 2016-04-25, and its primary completion date is 2018-07-10.

Participants were assigned to groups receiving LY3303560 or saline solution. The listed treatment groups cover single intravenous doses of 7 mg, 21 mg, 70 mg, 210 mg, 700 mg, 1400 mg, 2800 mg, and 5600 mg, as well as a 210 mg subcutaneous dose. The saline solution group received an intravenous infusion intended to match LY3303560. The arm descriptions characterize the listed dose regimens as being given on Day 1 in healthy participants. The registry’s broader study description also includes participants with Alzheimer’s disease; the posted primary endpoint is defined for all enrolled participants, rather than as a separate result for each participant type.

The study summary describes monitoring of side effects and laboratory results. It also describes screening before the study and follow-up appointments, but does not provide a detailed schedule of endpoint assessments beyond the primary timeframe of baseline up to 146 days. The registry lists pharmacokinetic outcomes, including measures of drug concentration over time and cerebrospinal-fluid measures in participants with Alzheimer’s disease, as well as change in the QT/QTc interval.

The record does not report the randomization procedure, allocation concealment, masking procedures, dose-escalation decision rules, or a statistical analysis plan. It also does not give a detailed account of participant flow or explain how the listed group sizes relate to the total enrollment. Those details 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.

Only the first 6 of 10 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled participants.

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.

Only the first 6 of 11 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) to be Related to Study Drug Administration, measured over Baseline up to 146 days.

The primary endpoint is the number of participants with one or more serious adverse events considered by the investigator to be related to study drug administration. The timeframe is baseline up to 146 days, and the endpoint population is all enrolled participants. It is a participant-count outcome: a participant who experienced at least one event meeting the definition contributes to the count, rather than each separate event necessarily being counted as a separate participant.

Serious adverse events and investigator-attributed relatedness are distinct concepts. Seriousness concerns the event’s classification, while relatedness reflects the investigator’s assessment of whether it was associated with study drug administration. This endpoint therefore captures a particular subset of safety reports; it is not a count of all adverse events, nor does it summarize their severity, duration, or clinical course.

In an early-phase study, a safety endpoint is used to describe observed events during exposure and follow-up. It is not an efficacy measure. The registry reports zero participants with a related serious adverse event in each listed group. The separate adverse-event listing also distinguishes serious events, other nonserious events, and deaths. Those categories should not be conflated: a zero count for the primary endpoint does not mean that no nonserious adverse events occurred.

The registry does not report a formal definition of seriousness, event-level details for the primary endpoint, or the process used to determine relatedness beyond identifying the investigator as the assessor. The summary of other nonserious adverse events and all serious adverse events regardless of causality is referred to in the record’s adverse-events information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted endpoint is binary at the participant level: each participant either had one or more qualifying related serious adverse events during the stated timeframe or did not. This kind of outcome is commonly summarized with counts and denominators. The registry gives group counts and participant numbers, but does not post a formal estimate comparing a LY3303560 group with placebo. A count of zero is a descriptive observation, not a complete estimate of the possible event risk.

What does a confidence interval add?

In general, a confidence interval communicates the uncertainty around an estimated quantity. It helps distinguish a point estimate from the range of values that remain compatible with the data under the chosen statistical method. With rare or unobserved events and limited group sizes, uncertainty can remain substantial even when the observed count is zero. No confidence interval for the primary outcome is reported in the registry record, so no interval-based precision statement can be made from the posted primary results.

Why is there no two-group calculation?

The registry’s analysis information lists no analyses, and the binary comparison is identified as not estimable because values are missing or not estimable for a two-arm comparison. The posted outcome is zero in all listed groups. The registry therefore does not provide a recalculated effect estimate or a sample-size illustration based on an estimable observed contrast for this endpoint. A non-estimable comparison is not evidence that groups are equivalent; it means the posted information does not support that calculation.

In general, comparisons of binary outcomes require a defined contrast, such as a difference in the probability of an event between groups, together with a method for estimating its uncertainty. The choice of method can matter when event counts are sparse. A standard approximation may be unreliable when cells contain very few or no events, while other methods may be considered depending on the design and estimand. The registry record does not identify a method selected for this endpoint, so it would be inappropriate to assign one retrospectively or present an unreported test.

What do the group sizes and counts describe?

The listed group sizes are the participant counts associated with the posted arms. The primary endpoint specifies all enrolled participants as its population, while the record does not provide a detailed accounting of exclusions, missing endpoint data, or analysis-set membership. The endpoint counts should therefore be read according to the registry’s stated population definition, without assuming additional eligibility or evaluability rules. The record does not report whether any participants lacked follow-up or how incomplete observations were handled.

General statistical interpretation also depends on whether participants are analyzed according to their assigned groups, whether any observations are censored or excluded, and whether outcome assessment is complete. Those details are not reported in the registry record. Randomized allocation and double masking are listed design features, but the methods used to implement them and the analysis procedures are not described in the posted record.

How should the dose groups be considered?

The study is described as dose escalation, and the registry lists multiple LY3303560 dose groups and routes. These groups are useful for presenting the observed safety experience across the regimens in the record. They do not, by themselves, establish a dose-response relationship. Such an interpretation would require a defined analysis and adequate information about the groups, participant characteristics, follow-up, and outcomes. No dose-response model or trend analysis is reported.

The placebo group is listed as a comparator, but the registry does not post a formal estimate for each dose against placebo. The group summaries remain descriptive. In general, randomization can support comparisons by balancing factors across groups on average, but the reliability of a specific comparison also depends on its prespecified analysis, data completeness, and precision. Those elements cannot be assessed fully from the registry record.

What do planning illustrations mean?

In general, a sample-size calculation is a planning exercise based on assumptions about the outcome frequency, target effect, allocation, significance level, and desired power. It is not an observed property of a completed study and should not be described as observed power. The record’s planning assumptions describe a normal approximation, equal allocation, a two-sided significance level of 0.05, and planning for a stated fraction of an observed effect. However, the primary binary comparison is not estimable from the posted zero-event summaries, and no primary-outcome sample-size calculation is reported. These planning concepts should not be mistaken for a justification of this trial’s enrollment.

Multiplicity refers to the statistical consequences of making multiple comparisons or testing multiple outcomes. This study lists several secondary outcomes, but the registry does not report a multiplicity adjustment or a testing hierarchy. The absence of a reported adjustment does not establish that none was used; it means the approach is not reported in the registry record. Likewise, methods for missing data, interim looks, and analysis populations beyond the stated primary population are not reported. The primary results can therefore be described, but the inferential framework cannot be reconstructed from the posted information.

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", "7 mg LY3303560", "21 mg LY3303560", "70 mg LY3303560", "210 mg LY3303560", "210 mg LY3303560 SC")
n      <- c(17, 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  Placebo  17  0  0.0  0.0  19.5  0.0  18.4  0.1  18.5
ARM  7 mg LY3303560  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  21 mg LY3303560  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  70 mg LY3303560  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  210 mg LY3303560  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  210 mg LY3303560 SC  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 five secondary outcomes, covering pharmacokinetic measures, cerebrospinal-fluid pharmacokinetic measures in participants with Alzheimer’s disease, and mean change from baseline in the QT/QTc interval. It does not report a hierarchy among these outcomes, a prespecified testing sequence, or a method for controlling multiplicity. With several outcomes, general statistical practice recognizes that repeated testing can affect the chance of obtaining a nominally unusual result by chance. Whether and how that concern was addressed is not reported in the registry record.

The registry lists no analyses for the posted results. It does not provide analysis-specific populations, model specifications, covariate adjustments, or handling of missing outcome data. The primary endpoint population is described as all enrolled participants, but this statement does not establish whether all enrolled participants had complete follow-up or were included in every analysis. Missingness, withdrawals, and exclusions are not described in enough detail to evaluate their impact.

No interim analysis plan or sample-size justification is reported in the registry record. The available information also does not establish whether an analysis plan existed outside the registry. These omissions limit assessment of how outcomes and comparisons were selected, how incomplete information was treated, and whether inferential procedures were adjusted for multiple outcomes or dose comparisons.

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 primary safety result is the number of participants with one or more serious adverse events judged by the investigator to be related to study drug administration. The posted count is zero in the placebo group and zero in each listed LY3303560 group. The registry also reports zero deaths in the listed groups. These are counts observed during the reported study, not proof that serious events or deaths cannot occur.

The separate adverse-event information reports other nonserious adverse events: 6 participants in the placebo group; 1 each in the 7 mg, 21 mg, and 70 mg groups; 2 each in the 210 mg intravenous, 210 mg subcutaneous, and 1400 mg groups; 3 in the 700 mg group; 1 in the group labeled 2600 mg; and 4 in the 5600 mg group. These counts are distinct from the primary endpoint and should not be read as serious related events. The record labels this group 2600 mg, while another arm listing identifies 2800 mg, an inconsistency that should remain explicit.

These summaries do not give event descriptions, severity grades for nonserious events, timing, recurrence, or individual attribution. They support a descriptive reading of what was reported, not a precise comparison of safety between regimens.

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

The result means that the registry reports no participants with a serious adverse event considered related to study drug administration in any listed treatment group during baseline up to 146 days. It also reports other nonserious adverse events and provides counts by group. The result is a record of observed events in this study, with its listed group sizes and follow-up period.

It does not mean that LY3303560 has no serious safety risk. In general, an event that was not observed in a study group may still occur, particularly when the available group is limited in size or the event is uncommon. The registry supplies no confidence interval or other inferential estimate to quantify uncertainty around the zero counts. Nor does it show a formal safety comparison between each dose and placebo.

It also does not establish that LY3303560 is effective for Alzheimer’s disease. The study is described as a phase 1 safety, tolerability, and pharmacokinetic investigation, and the primary endpoint is a safety measure. The posted primary endpoint does not measure cognitive change, disease progression, or clinical benefit. The registry’s secondary outcome list includes pharmacokinetic and QT/QTc measures, but the record does not provide results for those outcomes in the registry record for this analysis.

Interpretation is further limited by the lack of separate primary outcome results for healthy participants and participants with Alzheimer’s disease, the absence of reported missing-data methods and inferential analyses, and the inconsistency between the 2600 mg adverse-event label and the 2800 mg arm listing. The most defensible conclusion is therefore narrow: no related serious adverse events were recorded in the posted group summaries during the stated follow-up, while the registry does not establish a zero underlying risk or a clinical treatment effect.

14. Why This Trial Matters Statistically

This trial illustrates a central statistical feature of early-phase safety studies: a result can be clinically important to monitor even when the posted endpoint contains no events. Zero observed events are straightforward to report, but they do not remove uncertainty about events that might occur outside the observed participants or follow-up. The distinction between an observed count and an estimate of underlying risk is essential when reading small group summaries.

The design also includes several dose levels and two administration routes. That structure can describe safety observations across regimens, but it raises questions about how groups are compared, how dose-related patterns are assessed, and how multiple outcomes are handled. The registry does not report the analysis strategy for those questions. Without that information, the group summaries should remain descriptive rather than being interpreted as a formal dose-response analysis or a set of comparative tests.

The study combines a broad population description with arm descriptions focused on healthy participants, while the primary population is stated as all enrolled participants. Because the posted primary outcome is not separated by participant type, the record does not permit a direct comparison of safety experience between healthy participants and participants with Alzheimer’s disease.

Finally, the inconsistent dose label in the adverse-event listing demonstrates why registry data require careful reading across outcome and arm records. A discrepancy should be noted rather than silently corrected. In combination, sparse event counts, absent inferential analyses, missingness details that are not reported, and a labeling inconsistency show why transparent reporting of definitions, denominators, analysis methods, and group populations matters for interpreting early clinical evidence.

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 main limitation is the sparse primary endpoint: no related serious adverse events are recorded in any listed group, and the registry provides no confidence intervals or formal comparisons. The posted data therefore describe observed counts but do not quantify the precision of a risk estimate or establish equivalence between LY3303560 and placebo.

The record does not give outcome results separately for healthy participants and participants with Alzheimer’s disease, despite describing both populations. It also does not report detailed participant flow, withdrawals, missing observations, or how missing endpoint data were handled. The stated primary population is all enrolled participants, but the record does not offer enough detail to assess completeness of follow-up for that population.

Important statistical details are not reported in the registry record, including the randomization and masking procedures, a statistical analysis plan, the method for any planned comparisons, multiplicity handling, interim analyses, and the enrollment justification. The registry lists no analyses. These omissions prevent assessment of whether the posted descriptive summaries correspond to prespecified analyses or whether adjustment was planned for multiple outcomes or dose comparisons.

The adverse-event listing contains a dose-label discrepancy: it identifies a group as 2600 mg, while the intervention and primary arm listings identify a 2800 mg group. The record does not explain the difference. Event-level descriptions and additional detail on nonserious event severity and timing are also not included in the information. The registry’s secondary outcomes are listed, but their results are not part of the registry entries analyzed in this explanation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY3303560 in Healthy Participants and Participants With Alzheimer's Disease (AD) — NCT02754830.
• Registry record last updated 2023-10-13; status last verified 2023-10.
• Results first posted 2023-09-21.
• 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

NCT02754830 is a completed phase 1 randomized, double-blind, parallel-group study of single-dose LY3303560 in healthy participants and participants with Alzheimer’s disease. The registry records enrollment of 72 and describes intravenous dose groups, a subcutaneous dose group, and an intravenous saline comparator. The primary endpoint is the number of participants with one or more serious adverse events considered related to study drug administration from baseline up to 146 days.

The posted primary outcome is zero in every listed group. Other nonserious adverse events are reported, and deaths are recorded as zero. No inferential analyses or confidence intervals are reported for the primary endpoint, and a two-arm binary comparison is not estimable from the posted information. Results are not separated by participant type. An adverse-event group is labeled 2600 mg in one listing, while other registry listings identify 2800 mg. These findings are descriptive safety observations and do not establish treatment efficacy or absence of risk.