A Study of LY3050258 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3050258 in Healthy Participants (NCT02121834), 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

This is a safety-focused question in healthy participants, not a question about treatment of a disease. The registry record also lists pharmacokinetic outcomes concerning AUC τ,ss and Cmax. Their numerical results are not reported in the registry record. The posted serious-event result therefore addresses a specific safety endpoint and does not, by itself, describe all safety findings or the pharmacokinetic profile.

3. Trial Design

The registry record describes a Phase 1, randomized, double-masked, parallel study of LY3050258 and placebo. The official title characterizes it as a multiple-dose, dose-escalation, safety, tolerability, and pharmacokinetic study. Enrollment was 63, and the study status is completed. The record lists a start of 2014-06 and primary completion of 2014-12.

Five active-dose cohorts received daily LY3050258 for 28 days: Cohort A received 10 mg, Cohort B 30 mg, Cohort C 90 mg, Cohort D 180 mg, and Cohort E 360 mg. Matching placebo was also given daily for 28 days. The reported placebo groups are separated into Cohorts A-D and Cohort E. The registry record does not describe the allocation procedure, the number of participants planned for each cohort, or the exact sequence and timing of dose escalation.

The study brief describes an approximately 14-week study, including a 2 week follow-up appointment after the last treatment with study drug. The primary endpoint timeframe is baseline to study completion, up to 14 weeks. Its analysis population is all participants who received at least one dose of study drug. The arm-specific counts reported for that endpoint are 12 for Cohort A-D placebo, 11 for 10 mg, 9 for 30 mg, 10 for 90 mg, 9 for 180 mg, 9 for 360 mg, and 3 for Cohort E placebo.

The record does not report further design details such as stratification, concealment procedures, or cohort-specific randomization. It also does not report a protocol-based sample-size justification or the statistical analysis plan. These absences limit how fully the design and the intended analysis can be reconstructed from the registry record alone.

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 7 groups are shown.

Overall Study

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.

Only the first 6 of 8 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 to Study Completion (Up to 14 Weeks).

The primary endpoint counts participants with one or more serious adverse events (SAEs) that the investigator considered related to study drug administration. It covers baseline through study completion, up to 14 weeks, and includes participants who received at least one dose. The endpoint is a participant count: a participant meeting the definition is counted as having the endpoint, rather than the result measuring the number of separate events.

This type of endpoint is used in safety monitoring to focus attention on serious events judged related to the study drug. Its investigator-relatedness condition is important: the primary count is not the same as a count of every SAE, nor does it include all nonserious adverse events. The registry description says clinically significant events were defined as serious and other nonserious adverse events related to study drug; it directs readers to the reported adverse-events information for other nonserious AEs and all SAEs, regardless of causality.

In this study, the primary endpoint is reported as 0.0 participants in each listed arm. Other nonserious adverse events are reported separately, so the zero primary count should not be read as an absence of all adverse events. The endpoint also does not measure pharmacokinetics, which are listed as secondary outcomes. Its scope is the participant-level count of serious, investigator-related events over the stated follow-up period.

7. Results Posted in the Registry

• 10 mg LY3050258: 0.0% (0/11) versus 0.0% (0/12) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• 90 mg LY3050258: 0.0% (0/10) versus 0.0% (0/12) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

For the primary endpoint, the registry reports counts of participants with one or more investigator-related SAEs. This is a binary outcome at the participant level: each person either met the endpoint definition or did not. The posted arm values are 0.0 for Cohort A-D placebo, 10 mg, 30 mg, 90 mg, 180 mg, 360 mg, and Cohort E placebo. The associated arm counts are the numbers included in those reported endpoint summaries.

What does a risk difference describe?

A risk difference contrasts the proportion with the event in one arm against the proportion in another arm. A value of 0.0 indicates that the observed proportions in the two compared arms are the same. In the posted comparisons, the event count is zero in both arms, so each reported risk difference is 0.0. This is a descriptive contrast of the data; it should not be interpreted as proof that the true risks are identical.

The registry lists comparisons of 10 mg and 90 mg LY3050258 with Cohort A-D placebo. Each comparison has a reported interval from 0.0 to 0.0. The calculation method is not reported in the registry record. With no endpoint events in either group, a numerical interval that has no width should be read cautiously: it does not make the finite study more informative about rare events than its participant counts allow. The record does not identify the interval procedure or explain how zero-event data were handled.

Why do counts and proportions need context?

Counts should be read alongside the number of participants at risk in each arm. A count of zero in an arm of 3 participants and a count of zero in an arm of 12 participants are both zero observed events, but the amount of information about uncommon events differs with the number observed. More generally, an estimate describes the study data, while its uncertainty depends on both the observed outcomes and the analysis method. The registry does not report a formal uncertainty method for the primary arm counts.

For binary safety outcomes, sparse data and zero counts can make conventional comparative analyses difficult. A method may need to account for the fact that estimates based on observed proportions can be unstable when events are uncommon or absent. This is a general statistical point, not a claim about which method the trial used. The registry record does not report a model, adjustment, test, or inferential procedure for the primary endpoint.

What is and is not included in the reported comparisons?

The posted comparison results cover only 10 mg and 90 mg against Cohort A-D placebo. They are reported as risk differences, with point estimates and confidence limits. No p-values or adjusted comparisons are reported. The other active dose arms have primary endpoint counts, but no corresponding risk-difference comparisons are listed. Cohort E placebo is reported separately and is not the comparator in the listed comparisons.

Randomization and masking are design features that can help limit systematic differences and influence during a trial. The registry labels this study randomized and double-masked, but does not report operational details about the randomization sequence, masking procedures, or how masking was maintained. The record also does not describe whether comparisons were adjusted for cohort structure or other factors. No such analysis should be assumed from the design labels alone.

What can planning calculations tell readers?

Planning calculations are prospective illustrations of the sample size that might be needed under stated assumptions; they are not a measure of power achieved by the completed study. The registry's sample-size assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. The record does not report the trial's own design justification, and the planning assumptions should not be mistaken for that justification.

For count outcomes, a difference in event frequency is meaningful only in relation to the event definition and the follow-up period. The primary endpoint concerns participants with one or more investigator-related serious events up to 14 weeks, not all events or all time beyond the study. The study also lists pharmacokinetic outcomes, including AUC τ,ss and Cmax, but numerical results for those outcomes are not reported in the registry record. Thus the serious-event count cannot stand in for those distinct measurements.

In general, sound interpretation combines the endpoint definition, the population analyzed, the observed counts, an appropriate uncertainty method, and the broader analysis plan. The registry supplies the endpoint definition and counts, but does not report enough information to identify the full inferential approach. The results can therefore be described directly, while stronger claims about differences, rare-event risk, or analysis intent remain unsupported by the registry record.

10. Confidence Intervals and Precision

Precision concerns how narrowly study data locate an underlying quantity, such as an event risk or a difference between arms. A confidence interval is a range calculated by a specified method to reflect uncertainty around an estimate. Its meaning depends on the method and assumptions; it does not guarantee that the true value falls inside the reported range.

For the primary endpoint, every arm has a reported count of 0.0. The two listed risk-difference comparisons, 10 mg and 90 mg versus Cohort A-D placebo, each have an estimate of 0.0 and limits of 0.0 to 0.0. Although these displayed limits have no numerical width, the registry record does not report how they were calculated. In a study with zero observed events in the compared arms, a zero-width interval should not be taken as evidence that the underlying risk is known without uncertainty.

The number of participants is relevant to precision. The endpoint counts are reported for 12.0 participants in Cohort A-D placebo, 11.0 at 10 mg, 9.0 at 30 mg, 10.0 at 90 mg, 9.0 at 180 mg, 9.0 at 360 mg, and 3.0 in Cohort E placebo. These group sizes and the absence of primary events limit the information available about uncommon serious events. No alternative interval estimates or uncertainty analyses are reported in the registry record.

Precision also depends on which contrast is being considered. Confidence intervals are listed only for the comparisons involving 10 mg and 90 mg, each against Cohort A-D placebo. There are no reported intervals for the other dose arms. The two available comparisons should not be generalized to unreported contrasts, and they do not quantify uncertainty in pharmacokinetic outcomes or nonserious adverse events.

Accordingly, the posted result is precise as a description of what was counted in these arms, but the broader risk is not precisely established by the displayed zero-event results. The registry does not report the confidence-interval method, and the reported interval limits alone do not resolve that limitation.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and two secondary pharmacokinetic outcomes: AUC τ,ss and Cmax after multiple doses of LY3050258. It reports 3 outcome measures and 0 analyses. The registry record does not report a statistical plan describing how these outcomes were prioritized, tested, or interpreted together. Numerical results for the two listed pharmacokinetic outcomes are not reported in the registry record.

When a study considers several outcomes, doses, or comparisons, multiplicity can affect how often apparently notable findings arise by chance. A prespecified approach may control or otherwise address that issue. Whether the study used such an approach, and whether the listed comparisons were prespecified, are not reported in the registry record. No multiplicity adjustment should be assumed. The two posted risk-difference comparisons should be understood as the comparisons listed, not as evidence that all doses were tested in the same way.

The primary endpoint population is described as all participants who received at least one dose of study drug. The registry record does not report a separate intention-to-treat population, a per-protocol population, or the handling of participants who did not complete follow-up. It also does not report the number of missing endpoint assessments, how missing values were treated, or whether participants with incomplete observation were included in a particular way. These details matter because the endpoint spans baseline through study completion, up to 14 weeks.

The completed study enrolled 63 participants, but the primary endpoint summaries provide arm-specific counts rather than a description of participant flow. The record does not report a protocol-based sample-size justification, an interim-analysis plan, or an analysis plan for safety comparisons. It therefore is not possible to determine from the registry alone whether the final outcome reporting followed a prespecified analysis strategy or how unreported data were handled.

These omissions do not change the reported observed counts. They do limit assessment of the statistical context around the results, including the scope of comparisons, missing-data assumptions, and interpretation of multiple outcomes.

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 figures count participants with one or more serious adverse events that the investigator considered related to study drug administration. The registry reports 0.0 such participants in Cohort A-D placebo, 10 mg, 30 mg, 90 mg, 180 mg, 360 mg, and Cohort E placebo. This specific endpoint is not equivalent to all serious events or all adverse events.

The adverse-event listing separately reports zero related serious adverse events for each group. It also reports other nonserious adverse events in 5 participants in Cohort A-D placebo, 4 at 10 mg, 2 at 30 mg, 3 at 90 mg, 6 at 180 mg, 4 at 360 mg, and 2 in Cohort E placebo. These other-event counts show why a zero primary endpoint cannot be read as no adverse events of any kind. The registry description says all SAEs, regardless of causality, and other nonserious AEs are addressed in the reported adverse-events information.

No deaths are listed as counts in the registry record, and the list of top serious terms is empty. The record does not give additional detail in the registry record about individual nonserious event terms, timing, duration, or severity. The counts should therefore be interpreted within their reported categories and should not be extended to outcomes not described.

These safety counts describe the participants observed during this study and its follow-up. They do not establish how frequently rare events might occur in a larger population or over a longer observation period.

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

The primary finding is straightforward: no participant in any listed arm was counted as having an investigator-related SAE during the endpoint timeframe. The registry also reports two risk-difference comparisons, for 10 mg and 90 mg versus Cohort A-D placebo, both with an estimate of 0.0 and reported limits from 0.0 to 0.0. These are descriptions of the posted data, not proof that the dose groups and placebo have identical underlying risks.

The result does not mean that no adverse events occurred. Other nonserious adverse events are reported in each treatment and placebo group. Nor does it establish that serious events cannot occur; the number of participants observed in each arm is limited, and uncommon outcomes may not appear in a study of this size. The record reports enrollment of 63, with arm-specific endpoint counts ranging from 3.0 to 12.0 participants.

The finding applies to the endpoint as defined: at least one serious event considered related by the investigator, among participants who received at least one dose, from baseline to study completion, up to 14 weeks. It does not describe all SAEs regardless of causality, every nonserious event, or outcomes after the stated follow-up. The primary result also does not answer the listed pharmacokinetic questions about AUC τ,ss and Cmax.

The trial is described as randomized, double-masked, and parallel, but the registry does not report detailed procedures or the statistical analysis plan. It lists comparisons for only two active doses, and the method behind their confidence intervals is not reported. Accordingly, the results do not support claims about unlisted dose comparisons, long-term safety, other populations, or the overall benefit-risk balance of LY3050258.

The appropriate statistical reading is bounded: the registry records no primary-endpoint events in the observed arms, while broader conclusions remain uncertain because of the study's limited size, endpoint scope, and missing analysis details.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how safety endpoints and sparse binary data need to be read together. A zero count is an observed result, but it does not alone provide a precise estimate of the risk of a rare event. The arm sizes matter, as does the distinction between the primary endpoint and broader adverse-event reporting.

The endpoint is narrowly defined around serious events judged by the investigator to be related to study drug. That definition makes the reported result interpretable, but also means it should not be substituted for all-cause SAEs or all adverse events. The separate reports of other nonserious events reinforce the importance of keeping safety categories distinct.

The registry also illustrates why the presence of confidence limits does not remove the need to understand the analysis method. For both listed risk-difference comparisons, the point estimate and interval limits are 0.0. The interval calculation method is not reported, so those values should be read alongside the zero event counts and small arm sizes rather than as definitive evidence of no uncertainty.

Finally, the design combines multiple doses with placebo groups organized by cohort, while posted comparative estimates cover only two active doses against Cohort A-D placebo. The record does not report the prespecified statistical plan, multiplicity handling, or missing-data approach. Those details affect how readers assess the scope of statistical conclusions. This makes the record useful for distinguishing what is directly observed from what cannot be determined from the posted results.

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 study enrolled 63 participants, with endpoint counts reported for relatively small arms. Zero primary-endpoint events in these groups provide limited information about uncommon serious events. The reported results apply to the study's healthy-participant population and its follow-up, rather than establishing event risks in other populations or over longer periods.

The endpoint definition is specific: it counts participants with one or more serious adverse events judged by the investigator to be related to study drug. The result does not summarize all SAEs regardless of causality, all nonserious events, or all possible safety outcomes. The separate counts of other nonserious AEs are not accompanied by event terms or further clinical detail.

Comparative estimates are listed only for 10 mg and 90 mg LY3050258 against Cohort A-D placebo. The record does not report corresponding comparisons for 30 mg, 180 mg, or 360 mg, and it separates Cohort E placebo from Cohort A-D placebo. The method used for the reported confidence intervals is not reported, although both displayed intervals have limits of 0.0 to 0.0.

The registry record does not report the statistical analysis plan, multiplicity handling, missing-data procedures, participant flow, or a protocol-based sample-size justification. It also does not provide numerical findings for the listed secondary pharmacokinetic outcomes. These limitations restrict assessment of the analysis strategy and make it difficult to extend the primary safety result beyond its direct descriptive meaning.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY3050258 in Healthy Participants — NCT02121834.
• Registry record last updated 2018-07-27; status last verified 2018-07.
• Results first posted 2018-07-27.
• 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

NCT02121834 is a completed Phase 1 randomized, double-masked, parallel study of LY3050258 in healthy participants. Enrollment was 63. Participants received daily LY3050258 at 10 mg, 30 mg, 90 mg, 180 mg, or 360 mg, or matching placebo, for 28 days.

The primary outcome counted participants with one or more serious adverse events considered related to study drug, from baseline to study completion, up to 14 weeks. The reported count is 0.0 in each of the five active-dose arms and both placebo groups. Other nonserious adverse events were reported separately. Two risk-difference comparisons are listed, for 10 mg and 90 mg versus Cohort A-D placebo; both estimates and reported confidence limits are 0.0.

The registry lists pharmacokinetic outcomes for AUC τ,ss and Cmax, but their numerical results are not reported in the registry record. The statistical analysis plan, confidence-interval method, multiplicity approach, and missing-data handling are also not reported.