A Study of LY2969822 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2969822 in Healthy Participants (NCT02018887), a randomized phase 1 study. The primary outcome is Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration.

2. Clinical Question

The study was a randomized, double-blind, phase 1 trial. Its stated purpose was to assess safety and tolerability and to measure how much study drug entered the bloodstream and how long it took the body to eliminate it. The record also lists pharmacokinetic outcomes for the prodrug LY2969822 and its active metabolite, including maximum plasma and cerebrospinal fluid concentrations and area-under-the-curve measures.

The registry says this was the first time the study drug was given to participants and that the study was for research purposes, not treatment of a medical condition. It therefore addresses early safety and drug-exposure questions in healthy volunteers, rather than whether the drug benefits people with a disease. The primary endpoint is a defined safety count over the study period; the registry does not report a formal comparative estimate for that endpoint.

3. Trial Design

The registry classifies this as a phase 1, randomized, double-blind, crossover study. Enrollment was 99. The study began in 2013-12, primary completion was 2015-02, and the status is completed. The sponsor is Eli Lilly and Company.

The study title describes single- and multiple-ascending-dose evaluation of safety, tolerability, pharmacokinetics, and pharmacodynamics. The record divides the regimens into Parts A, B, and C. In Part A, the arm descriptions specify single oral doses in two of three study periods for LY2969822 and one of three periods for placebo. Parts B and C are described as oral administration for 14 days. The posted groups include several dose levels and schedules, including once-daily and twice-daily regimens, as well as titration schedules.

Although the study is classified overall as crossover, its displayed cohorts and arms cover several dose regimens and study parts. The record does not describe the sequence-generation method, the allocation ratio, washout procedures, or which participants crossed between which specific treatments. Those details are not reported in the registry record. The crossover label alone is not enough to assume that every listed dose group formed a direct within-participant comparison with every placebo group.

Randomization and double masking are design features intended, in general, to reduce systematic differences in treatment allocation and expectations about assigned treatment. Their implementation details, including who was masked and how the masking was maintained, are not reported in the registry record. Likewise, the record does not provide a protocol-level account of the dose-escalation decision rules or of how individual cohorts were assigned to the study parts.

The registry describes healthy volunteers, and its summary says the study was not intended to treat a medical condition. That setting and stated purpose matter when interpreting the safety findings: the result concerns the reported participants and study period, and is not itself a test of treatment benefit in a patient population. The stated primary-endpoint population is all participants who received at least one dose of study drug.

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 had 3 parts. Part A-Single ascending dose, 3-period, crossover study (Cohorts 1-2). Part B-Multiple ascending dose, parallel study (Cohorts 3-7). Part C-Multiple dose, single dose level study (Cohort 8). Each participant enrolled in 1 cohort. Replacement participants received interventions intended for those that discontinued early.

Only the first 6 of 11 groups are shown.

Part A: Cohorts 1-2: Period 1

Part A: Cohorts 1-2: Period 2

Part A: Cohorts 1-2: Period 3

Reasons for not completing this period:

Part B: Cohorts 3-7 Overall

Reasons for not completing this period:

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration, measured over Baseline Through End of Study (up to Week 7).

The primary endpoint counts participants with one or more serious adverse events (SAEs) that the investigator considered related to study drug administration. Its timeframe is baseline through end of study, up to Week 7, and the stated population is all participants who received at least one dose of study drug. The registry reports the outcome as a number of participants, rather than as a continuous measure of symptoms, drug concentration, or time to an event.

This type of endpoint is used in safety monitoring because serious events can be important even when they are uncommon. Counting participants with at least one qualifying event gives a direct description of how many people in each group met the specified safety criterion. The attribution requirement is important: the primary endpoint is limited to events the investigator considered related to study drug, rather than all serious events regardless of suspected cause.

The record separately directs readers to its reported adverse events for a summary of other nonserious AEs and all SAEs, regardless of causality. Those broader safety summaries answer a different question from the primary endpoint. An absence of investigator-attributed SAEs does not mean there were no other adverse events, and it does not establish that all possible harms have been ruled out.

The posted primary values are zero in every listed group. This is a descriptive result for the recorded participants and follow-up period. The registry does not provide a confidence interval, adjusted estimate, or formal comparison for the primary endpoint, so the result should not be read as a precise estimate of the underlying event risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available for this study is mainly descriptive. The primary outcome is a binary participant-level event count: each participant either had one or more qualifying serious adverse events or did not. The registry presents counts and group denominators. It does not report an inferential analysis for the primary outcome, and the listed analysis count is zero.

What does a zero count tell us?

For each reported group, the posted count is zero participants with one or more investigator-attributed SAEs. This directly describes what was recorded during the stated follow-up. It does not show that the underlying probability of such an event is exactly zero. In general, an observed count is subject to sampling uncertainty: another group of participants could have a different count even if the underlying conditions were similar. That uncertainty is especially relevant for uncommon events and groups with limited observations.

A confidence interval is a statistical range intended to communicate uncertainty around an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates more precision under the assumptions of the method. No confidence intervals are reported for the primary outcome in the registry record. Consequently, the zero counts cannot be paired with a registry-reported range that quantifies how uncertain the underlying event frequency may be.

Why is a two-group test not available?

The record identifies the binary comparison as omitted because values are missing or not estimable. With zero events listed throughout the groups, a conventional comparison may not yield a meaningful treatment contrast from these posted counts. The registry supplies no sponsor analysis or alternative model result for this endpoint. No p-value or estimate of a difference between LY2969822 and placebo is reported. The descriptive zero counts should therefore not be treated as evidence from a completed equivalence or non-inferiority test.

In general, statistical models for binary outcomes compare event probabilities or related measures, but such analyses require an estimable contrast and assumptions appropriate to the data structure. The study is classified as crossover, while its posted results are arranged by cohorts and dose groups. A crossover analysis may need to account for within-participant measurements and treatment sequence; a simple comparison of independent groups would not automatically capture that structure. The registry record does not report the analysis model, the handling of within-participant correlation, or the method used to assess period or sequence effects.

How do design and analysis connect?

Randomization and double masking are reported design features. In general, randomization is intended to limit systematic differences in assigned treatments, and masking is intended to reduce the influence of knowledge of assignment on care, reporting, or assessment. These design features do not by themselves define the statistical analysis. The allocation procedure, masking roles, and prespecified analysis plan are not reported in the registry record.

The record describes a crossover design overall, Part A single-dose periods, and 14-day regimens in Parts B and C. It also lists different dose levels, schedules, and cohorts. General statistical interpretation should respect those design distinctions rather than combine every listed group into one contrast. The registry does not report which contrasts were prespecified, how the cohort structure entered the analysis, or whether any covariate adjustment was planned.

For continuous pharmacokinetic outcomes, general analysis may summarize concentration or exposure using measures such as a mean, median, or model-based estimate, with an accompanying measure of variability or uncertainty. The choice depends on the outcome distribution and analysis objective. The registry lists maximum plasma concentration, maximum cerebrospinal fluid concentration, plasma area under the curve, and cerebrospinal fluid AUC(Tau) among secondary outcomes. Numerical estimates and statistical methods for these outcomes are not reported in the registry record, so no distributional or comparative conclusion can be drawn from their titles alone.

What do planning calculations mean?

The stated planning illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as targeting a stated fraction of the observed effect. In general, such calculations explore how much information a hypothetical study might need under specified assumptions; they are not a measure of the actual trial’s power after results are observed. The registry does not report that these assumptions were the original design basis for this trial, and the planning illustrations should not be described as observed power.

The record gives no sample-size justification, target effect, or formal power calculation for the trial’s original design. Those details are not reported in the registry record. Since the primary outcome has zero events in all posted groups and no comparison is estimable, a planning illustration based on an observed effect also cannot substitute for a sponsor analysis of the safety endpoint.

Multiplicity refers, in general, to the increased chance of false-positive findings when several hypotheses are tested. The record lists four secondary pharmacokinetic outcomes in addition to the primary outcome, but does not describe a multiplicity adjustment or a hierarchy of testing. Those analysis-plan details are not reported in the registry record. The existence of multiple endpoints does not, by itself, establish that formal hypothesis tests were conducted.

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("Cohort 1 - Placebo", "Cohort 1 - 2 mg LY2969822", "Cohort 1 - 20 mg LY2969822", "Cohort 1 - 40 mg LY2969822", "Cohort 2 - Placebo", "Cohort 2 - 6 mg LY2969822")
n      <- c(9, 6, 6, 5, 9, 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  Cohort 1 - Placebo  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Cohort 1 - 2 mg LY2969822  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 1 - 20 mg LY2969822  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 1 - 40 mg LY2969822  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Cohort 2 - Placebo  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Cohort 2 - 6 mg LY2969822  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 one primary safety endpoint and four secondary pharmacokinetic outcomes. The secondary outcomes concern maximum plasma concentration, maximum cerebrospinal fluid concentration, plasma area under the curve, and cerebrospinal fluid AUC(Tau), each for the prodrug LY2969822 and active metabolite LSN2934747. The analysis count is zero. Numerical secondary results and their inferential analyses are not reported in the registry record.

Multiplicity arises in general when several statistical hypotheses are assessed, because repeated testing can raise the chance of at least one false-positive finding. A prespecified testing hierarchy or adjustment procedure can address that issue, but neither is described in the registry record. It is also not reported whether these secondary outcomes were intended for formal hypothesis testing or descriptive pharmacokinetic characterization only. Without that information and the outcome estimates, no claim about multiplicity-adjusted evidence can be made.

The primary endpoint population is all participants who received at least one dose of study drug. The registry does not provide a full account of analysis populations for the secondary outcomes, crossover participants, or individual study parts. It does not report how many participants were excluded from any analysis, how deviations from assigned treatment were handled, or whether analyses followed assigned treatment or actual exposure.

Missing-data handling is not reported in the registry record. There is no description of missing outcome measurements, imputation, or sensitivity analyses. For pharmacokinetic measures, the record does not state how measurements below assay limits or incomplete sampling were handled. These omissions limit assessment of how complete the data were and whether the reported summaries, if considered separately, would depend on particular assumptions about missing observations.

12. 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 primary safety endpoint is narrowly defined: participants with at least one SAE considered by the investigator to be related to study drug administration. The posted count is zero in every listed placebo and LY2969822 group. This is a count of participants meeting that definition during baseline through end of study, up to Week 7; it is not a count of all adverse events.

The registry’s broader adverse-event listing separates serious events from other nonserious events and includes SAEs regardless of causality. It reports zero affected participants in the serious-event category in each listed group. The counts for other nonserious AEs are not all zero and vary across the displayed groups. Those broader data should not be conflated with the primary endpoint, which requires both seriousness and investigator-attributed relation to study drug.

The group sizes differ, and the registry does not provide uncertainty intervals for these safety counts. In general, observing no events in a group does not prove an event cannot occur; the precision of any estimate depends in part on the amount and completeness of observation. The registry record does not describe completeness of follow-up, detailed event narratives, or the methods used to assess relatedness. Accordingly, these figures are best read as recorded counts, not as proof of absence of risk.

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

The central result is descriptive: no participants in the posted groups were recorded as having one or more serious adverse events that the investigator considered related to study drug administration. The broader serious-event category also has zero affected participants in each listed group, while other nonserious adverse-event counts are present and vary by group. These are distinct safety summaries and answer different questions.

The result does not establish that LY2969822 and placebo have identical safety profiles. The registry reports no estimable two-arm comparison for the binary primary outcome and no inferential estimate, p-value, or confidence interval. Without such an analysis, the zero counts cannot be used to rule out differences between groups. In general, absence of observed events is not the same as proof that the underlying event probability is zero.

The result also does not establish that the drug is safe for every population, dose, duration, or setting. The record describes a phase 1 study in healthy volunteers, with single-dose and 14-day regimens and multiple dose schedules. It states that the research was not intended to treat a medical condition. The posted safety information therefore pertains to the groups and follow-up described in this trial, not to an unreported patient population or longer-term use.

Nor does the primary safety count answer whether the drug reached the bloodstream or cerebrospinal fluid, how exposure changed with dose, or how the active metabolite behaved. Those are pharmacokinetic questions listed among the secondary outcomes, and their numerical results are not reported in the registry record for this analysis. The safety count also does not measure clinical benefit.

In general, interpreting early-phase safety data requires attention to the event definition, observation period, group sizes, and uncertainty. Here, the registry provides the endpoint definition and counts but no confidence intervals, detailed analysis plan, or missing-data account. The strongest conclusion supported by the posted primary values is that no qualifying related SAE was recorded in any listed group during the reported study period. Stronger comparative or general safety conclusions are not established by these data alone.

14. Why This Trial Matters Statistically

This trial illustrates a common statistical challenge in early safety studies: important adverse events may be rare, while the study is organized around dose escalation and early characterization rather than a definitive comparison of clinical outcomes. A zero count is useful as a record of what occurred, but it carries uncertainty about how often an event might occur beyond the observed participants and follow-up. That distinction between observed data and underlying risk is central to reading small safety datasets.

The group-based presentation also highlights why design details matter. The registry classifies the study as randomized, double-blind, and crossover, yet the listed regimens span several cohorts, study parts, dose levels, and schedules. Statistical comparisons must reflect how treatments were assigned and how repeated or within-participant observations were collected. The registry does not report enough analytic detail to reconstruct those comparisons, and the primary binary comparison is explicitly not estimable.

The record also separates an investigator-attributed related SAE endpoint from broader adverse-event reporting. This is a useful reminder that safety outcomes depend on operational definitions: seriousness, attribution, and the observation window shape what a count represents. A zero count for one narrowly defined outcome should not be generalized to all adverse events.

Finally, this study’s stated pharmacokinetic aims are distinct from its primary safety count. Concentration and exposure outcomes can describe drug disposition, while adverse-event counts describe observed safety events. The registry lists both types of questions, but numerical pharmacokinetic findings are not reported in the record. Keeping outcome types separate avoids treating a safety count as evidence about exposure or clinical benefit.

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 registry provides limited detail for evaluating the primary outcome beyond its definition, group counts, denominators, population, and timeframe. No confidence intervals or inferential results are posted, and the binary two-arm comparison is marked as missing or not estimable. The analysis count is zero. As a result, the precision of the zero counts and any comparative effect cannot be assessed from the registry record.

The design is classified overall as crossover, but the listed cohorts and parts include different regimens. The registry does not explain the treatment sequences, participant-level crossover patterns, washout procedures, or the relationship between cohorts and planned comparisons. It also does not report the randomization procedure, masking implementation, or statistical model. These omissions make it difficult to assess whether a particular analysis would need to account for repeated observations, period effects, or other features of the crossover structure.

The primary endpoint relies on the investigator’s assessment that an SAE was related to study drug. Details of the relatedness assessment process are not reported in the registry record. The broader adverse-event listing helps distinguish related serious events from other reported events, but does not supply detailed case descriptions in the registry record for this analysis.

Missing-data methods, follow-up completeness, analysis exclusions, and sensitivity analyses are not reported. The record also does not provide numerical results for the secondary pharmacokinetic outcomes or a plan for handling multiple outcomes. These limitations mean that the posted safety counts can be described, but a broader assessment of data completeness, analysis robustness, or pharmacokinetic findings is not possible from the registry information alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY2969822 in Healthy Participants — NCT02018887.
• Registry record last updated 2019-02-21; status last verified 2019-02.
• Results first posted 2019-02-21.
• 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

NCT02018887 is a completed, randomized, double-blind, phase 1 crossover study sponsored by Eli Lilly and Company. It enrolled 99 healthy participants and evaluated oral LY2969822 in single-dose and 14-day regimens, with placebo groups across the listed study parts and cohorts. The registry dates the study start to 2013-12 and primary completion to 2015-02.

The primary endpoint counted participants with one or more serious adverse events considered by the investigator to be related to study drug administration, from baseline through end of study, up to Week 7. The posted count is zero in every listed group. The registry does not report an estimable two-arm comparison or inferential analysis for that endpoint.

Four secondary pharmacokinetic outcomes are listed, but their numerical results and analysis methods are not reported in the registry record. Missing-data procedures, multiplicity methods, and detailed crossover analysis plans are also not reported.