A Study of LY2928057 in Hemodialysis Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2928057 in Hemodialysis Participants (NCT01991483), 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, not a comparison of clinical benefit. The registry also describes evaluating how LY2928057 affects hemoglobin and lists pharmacodynamic outcomes involving iron measures and red blood cell measures. Those outcomes provide context for the study’s broader objectives, but they are not the primary endpoint examined. The posted primary outcome is a count of participants meeting a specific serious-event definition. It is therefore important to distinguish it from the separate adverse-event summaries, which include serious events regardless of causality and other nonserious events.

3. Trial Design

The registry describes a completed, phase 1, randomized, double-masked, parallel-group study sponsored by Eli Lilly and Company. Enrollment was 28. The study began in 2013-12, and primary completion was 2015-10. The brief summary says participation could last up to 26 weeks, while multiple doses of LY2928057 or placebo were given during a 6 week period.

The posted treatment groups are placebo, 300 mg LY2928057, 600 mg LY2928057, and 1000 mg LY2928057. The primary endpoint counts participants with one or more serious adverse events considered by the investigator to be related to study drug. The reported group sizes for this outcome are 7 for placebo, 6 for 300 mg, 11 for 600 mg, and 4 for 1000 mg. The endpoint population is all participants who received at least one dose of study drug.

The arm descriptions add an erythropoiesis stimulating agent (ESA) context: participants either discontinued their personal physician-prescribed ESA before treatment or reduced its dose. Both LY2928057 and placebo descriptions include the once-every-2-weeks and once-per-week schedules. The registry does not report how the dose groups were allocated across those schedules or across the discontinued-ESA and reduced-ESA subgroups.

Randomization and masking describe features of the trial design, but the registry record does not report the randomization procedure, allocation concealment details, or who was masked. It also does not report a sample-size justification. The short duration and phase 1 designation are part of the setting in which the results should be read; the posted counts are not a basis for conclusions about longer-term outcomes.

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 included three parts. Part A was dose escalation (placebo, 300, 600, or 1,000 milligrams \[mg\] LY2928057). Part B was dose expansion (placebo or 1000 mg LY2928057). Part C was optional, based on predefined pharmacodynamics criteria. Part C was not executed.

Dose Level: Placebo

Dose Level 300 mg

Dose Level 600 mg

Reasons for not completing this period:

Dose Level 1000 mg

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.

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 Day 137).

The primary endpoint is the number of 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 Day 137. The outcome is a participant count: a participant is counted if at least one event meets the stated seriousness and relatedness criteria. The endpoint population consists of participants who received at least one dose of study drug.

This measure is used to summarize an important aspect of safety during the observed study period. Seriousness and relatedness are distinct judgments: an event may be serious without being considered related to study drug. The registry separately points readers to its reported adverse-event section for other nonserious AEs and all SAEs regardless of causality. That distinction matters when comparing the primary count with the broader serious-event counts.

The posted primary values are zero in each group: placebo, 300 mg LY2928057, 600 mg LY2928057, and 1000 mg LY2928057. These values describe the endpoint as defined; they do not mean that no adverse events occurred. The separate safety summaries report serious events and nonserious events, including events not judged related to study drug. The endpoint also says nothing by itself about hemoglobin or the other pharmacodynamic measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each participant either did or did not have one or more qualifying events during the stated period. The registry presents the outcome as counts, with the number of participants at risk shown for each treatment group. This makes the event definition central to interpretation. Here, the event must be serious and considered by the investigator to be related to study drug administration. A serious event not considered related is outside this primary definition, even though it may appear in the separate adverse-event summaries.

What does a participant count show?

A count communicates how many participants met the endpoint in the observed group. It does not, on its own, quantify uncertainty or establish how likely the event would be in a different group of participants. In general, a proportion can summarize a count relative to the number observed, and an interval can show uncertainty around an estimate. The primary results are posted as counts, and the registry does not report a confidence interval for the endpoint. The group sizes are small, so the counts should be read as a description of this study rather than as precise estimates for a wider population.

General statistical explanation: when events are uncommon, a group may have no observed events even when the underlying event probability is not zero. The range of plausible probabilities can remain broad, especially with small groups. Therefore, zero observed related SAEs should not be translated into proof of no risk. No numerical uncertainty estimate should be inferred from the posted count alone.

Why is a treatment comparison not available?

The registry’s comparison results are not estimable for this binary outcome. The posted primary count is zero in the placebo group and zero in each LY2928057 dose group. A comparison based on these data does not yield an informative observed contrast in event counts. The registry record does not report a comparative p-value, confidence interval, or adjusted model estimate for this endpoint. This is not evidence that the groups are equivalent; it means the posted results do not provide a usable comparative estimate for this outcome.

General statistical explanation: comparative methods for binary outcomes use the pattern of events and non-events across groups. If the observed data do not distinguish the groups on the endpoint, an estimated difference can be uninformative or not estimable under the chosen procedure. Different methods may handle sparse data differently, but the registry record does not identify a method for a primary between-group analysis. A method should not be assumed.

How should the broader safety counts be distinguished?

The adverse-event summary reports serious events regardless of causality, while the primary endpoint restricts its count to events judged related to study drug. The summary lists serious-event participants in all four groups, including 2 of 6 in the 300 mg group and 1 of 4 in the 1000 mg group. Those figures do not replace the primary endpoint, because their event definition differs. The registry also says that other nonserious AEs and all SAEs, regardless of causality, are located in the reported adverse-events section. The serious-event terms listed there include Anaemia, Hypertension, Pneumonia, Syncope, Staphylococcal bacteraemia, and Ankle fracture; the record gives percentages but those terms should not be assigned to a particular dose group unless the posted table does so.

General statistical explanation: safety summaries often use more than one event definition because seriousness, timing, and suspected relationship to treatment answer different questions. A causality judgment is not the same thing as the occurrence of an event. Reading counts from different definitions as though they measure the same outcome can create an incorrect comparison.

What does the planning section mean?

The page includes sample-size planning illustrations based on the observed effect and stated assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are planning scenarios, not observed characteristics of this trial and not observed power. The registry does not report the trial’s own sample-size justification, and no planning result should be treated as a design feature of the study. With the primary endpoint counts all zero and the two-arm comparison not estimable, the illustrations cannot be read as evidence that the trial had a particular probability of detecting a safety difference.

General statistical explanation: power is a design-stage probability tied to an assumed effect, sample size, and analysis method. An observed result does not reveal the probability that the study would have detected an effect. Planning examples can help show how assumptions affect required sample size, but they do not change what the trial observed. No additional sample-size calculation or assumption should be inferred beyond the assumptions stated with the illustration.

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", "300 mg LY2928057", "600 mg LY2928057", "1000 mg LY2928057")
n      <- c(7, 6, 11, 4)
events <- c(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  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  300 mg LY2928057  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  600 mg LY2928057  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5
ARM  1000 mg LY2928057  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and multiple pharmacodynamic outcomes, including maximum change in hemoglobin, serum iron, transferrin saturation, reticulocyte hemoglobin concentration, reticulocyte count, red blood cell count, mean corpuscular volume, and mean corpuscular hemoglobin. It reports 14 secondary outcomes, but the record does not report a multiplicity adjustment strategy or explain how confirmatory claims across outcomes were controlled. Without that information, readers should not assume that the outcomes were tested as one family or that any particular adjustment was applied.

The analysis population for the primary outcome is stated as all participants who received at least one dose of study drug. The record does not report further details about analysis populations for the secondary outcomes, nor does it describe exclusions or departures from the stated population. It does not report a missing-data method, how incomplete follow-up was handled, or whether any participants had missing primary outcome assessments. These details are not reported in the registry record.

The record gives the primary outcome timeframe as baseline to study completion, up to Day 137. It also describes participation lasting up to 26 weeks. No additional explanation of follow-up timing, censoring, or assessment schedules for the primary endpoint is reported. The absence of these details limits assessment of whether every participant had comparable opportunity for event observation.

The registry lists no estimable two-arm analysis for this binary outcome. It does not report an inferential analysis plan, interim analyses, or a multiplicity procedure. These omissions should be treated as unavailable reporting, not filled in by assuming standard practice.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (33.3%), hypertension (33.3%), pneumonia (25.0%), syncope (25.0%), staphylococcal bacteraemia (16.7%).

The primary safety result counts participants with one or more serious adverse events judged by the investigator to be related to study drug. The count is zero in placebo and in each LY2928057 dose group. The group sizes are 7, 6, 11, and 4, respectively, for placebo, 300 mg, 600 mg, and 1000 mg. These are counts observed over the stated primary endpoint period, not proof that related serious events cannot occur.

The broader adverse-event summary uses a different definition: serious adverse events regardless of causality. It reports 0 of 7 participants for placebo, 2 of 6 for 300 mg LY2928057, 0 of 11 for 600 mg LY2928057, and 1 of 4 for 1000 mg LY2928057. Those values should be read separately from the primary related-event counts. The listed serious-event terms include Anaemia, Hypertension, Pneumonia, Syncope, Staphylococcal bacteraemia, and Ankle fracture, with percentages recorded in the registry. The record does not report deaths in the posted safety summary.

Because the groups are small and the endpoint definitions differ, neither set of counts should be treated as a precise estimate of comparative safety. The primary count addresses investigator-assessed related serious events; the broader summary captures serious events regardless of that assessment.

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

The posted primary data show zero participants with a serious adverse event considered related to study drug in each of the four groups. That statement is limited to the registry’s endpoint definition, the participants counted, and the period from baseline to study completion, up to Day 137. It describes what was recorded in this study; it does not show that serious adverse events are impossible or that the treatments have identical safety profiles.

The separate adverse-event figures show why the distinction in definitions matters. Serious events regardless of causality were reported among participants in the 300 mg and 1000 mg groups, while the primary endpoint counts no related serious events in any group. These summaries are not contradictory: one includes all serious events regardless of causality, and the other counts only events considered related by the investigator. The summaries also do not establish that a particular event was caused by treatment.

The study was randomized and double-masked, but the posted group counts are small. The record does not provide a comparative estimate or uncertainty interval for the primary endpoint, and the comparison is not estimable from the posted results. Consequently, the data cannot establish equivalence, rule out differences, or quantify a reliable dose-related pattern for this endpoint. A zero count should not be interpreted as a zero underlying risk.

The primary endpoint is a safety measure, while the study’s broader objectives include hemoglobin and pharmacodynamic measures. The primary result does not answer whether those measures changed, and the information does not establish a clinical benefit. The page should be read as a statistical account of recorded event counts, not as a recommendation about treatment.

Finally, these findings apply to this study’s hemodialysis participants and observed follow-up. The registry record does not provide enough detail to generalize the counts to other populations, longer follow-up, or different treatment settings. The result is most useful when kept alongside its event definition, group sizes, timeframe, and the broader adverse-event reporting.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary safety outcome is a participant count with zero qualifying events in every posted group. Such a result is easy to overread. It is a clear description of the observed data, but it does not establish that the underlying event probability is zero or that the groups have equivalent safety. The modest group sizes make that distinction especially important.

The record also illustrates how outcome definitions shape interpretation. The primary endpoint requires both seriousness and investigator-assessed relatedness. The separate adverse-event summary counts serious events regardless of causality and therefore presents a different view of the safety experience. Keeping those definitions separate prevents an apparent conflict between the zero primary counts and the serious-event counts in some groups.

There is also a useful lesson about estimability. A randomized design does not guarantee that every planned or potential comparison can be estimated from the observed results. Here, the registry does not provide an estimable two-arm comparison for the binary primary outcome. The design features alone cannot supply a treatment-effect estimate when the posted outcome data do not distinguish the groups.

Finally, the study highlights the difference between planning illustrations and trial evidence. Sample-size examples based on an assumed effect are not observed power and do not explain the study’s actual design rationale. The registry does not report that rationale. Reporting that distinction helps readers avoid interpreting a planning scenario as a result or as evidence that the study could rule out a safety difference.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint has few observations in each group, and all posted group counts are zero. The registry does not report confidence intervals or a comparative estimate for the endpoint, and the two-arm comparison is not estimable. As a result, the precision of any underlying event probability and the size of any between-group difference cannot be assessed from the primary result alone.

The primary outcome depends on an investigator judgment that an SAE was related to study drug. The record does not provide event-level adjudication details or further information about how relatedness was assessed. The broad SAE summary uses a different definition, counting events regardless of causality. These distinct summaries cannot be combined into one endpoint.

The study includes several dose groups and arm descriptions involving different ESA management and dosing schedules. The registry record does not report how participants were distributed across the schedule and ESA subgroups within each displayed dose group. It also does not report details of randomization, allocation concealment, or masking procedures. Those omissions limit evaluation of subgroup balance and implementation.

The primary endpoint timeframe is stated as up to Day 137, whereas the brief summary says each participant could be in the study for up to 26 weeks. The record does not explain the relationship between those descriptions. Missing-data handling, follow-up completeness, and the sample-size justification are not reported in the registry record. Deaths are not reported in the posted safety summary. These limitations restrict interpretation to the observed counts and the definitions and timeframes explicitly stated.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY2928057 in Hemodialysis Participants — NCT01991483.
• Registry record last updated 2019-03-07; status last verified 2019-03.
• Results first posted 2019-02-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed phase 1 study enrolled 28 hemodialysis participants and compared placebo with 300 mg, 600 mg, or 1000 mg LY2928057 in a randomized, double-masked, parallel-group design. The intervention descriptions specify intravenous dosing over 6 weeks and include once-every-2-weeks and once-per-week schedules, with participants either discontinuing or reducing their prescribed ESA dose before treatment.

The primary endpoint was the number of participants with one or more serious adverse events considered related to study drug, from baseline to study completion, up to Day 137. The posted count was zero in every group. Separate serious adverse-event summaries, which include events regardless of causality, reported 0 of 7 participants for placebo, 2 of 6 for 300 mg, 0 of 11 for 600 mg, and 1 of 4 for 1000 mg. The primary binary comparison is not estimable from the posted results. The record does not report confidence intervals, a sample-size justification, or details of missing-data handling.