A Study of LY2541546 in Healthy Postmenopausal Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2541546 in Healthy Postmenopausal Women (NCT01742078), 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

The study also set out to assess pharmacokinetics and pharmacodynamics following a single dose. The listed secondary outcomes include the area under the concentration curve for LY2541546 from time zero to infinity, change from baseline in lumbar spine bone mineral density, percent change from baseline in P1NP, and the number of participants with anti-LY2541546 antibodies. The record identifies these as secondary outcomes, but the available result set does not include their numerical findings.

The primary question is about a specific safety event: a serious adverse event judged by the investigator to be related to study drug. It is not a question about every adverse event, nor does it measure the drug’s pharmacokinetic or pharmacodynamic effects. Those distinctions matter when interpreting the zero counts: they describe the posted serious-event endpoint, rather than establishing that no other events occurred or that every aspect of safety was assessed by this measure.

3. Trial Design

This was a randomized, parallel-group, Phase 1 study described as a single-dose, dose-escalation investigation in healthy postmenopausal women. The registry record lists double masking for the overall study. It also identifies two 225 mg and 750 mg intravenous groups as open label; how masking applied across the other groups is not reported in the registry record.

The intervention groups covered five intravenous doses—7.5 mg, 25 mg, 75 mg, 225 mg, and 750 mg—and one subcutaneous dose of 150 mg. Two additional groups received open-label intravenous doses of 225 mg and 750 mg. Placebo was administered intravenously or subcutaneously. The record does not report the allocation procedure, how participants were assigned to the different dose groups, or the route distribution within the placebo group. Although the total enrollment was 60, the posted endpoint counts list group sizes of 6.0 for each LY2541546 group and 12.0 for placebo.

The study start is recorded as 2008-06, primary completion as 2010-06, and status as completed. The primary endpoint counted participants with one or more serious adverse events considered by the investigator to be related to study drug administration, over Day 1 through Day 85. The primary analysis population is described as all participants who received study drug.

The stated study purpose included assessing safety, tolerability, pharmacokinetics, and pharmacodynamics after a single dose. Four secondary outcomes are listed: LY2541546 area under the concentration curve from time zero to infinity, change from baseline in lumbar spine bone mineral density, percent change from baseline in P1NP, and participants with anti-LY2541546 antibodies. Numerical results for these secondary outcomes are not reported in the registry record. Details of dose-escalation rules, visit schedules beyond the primary endpoint timeframe, and the allocation ratio 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 9 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 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 study drug.

Only the first 6 of 10 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 Day 1 through Day 85.

The primary endpoint is the number of participants with one or more serious adverse events that the investigator considered related to study drug administration, assessed from Day 1 through Day 85. It is a participant count: an individual is counted for this endpoint if they experienced at least one qualifying event during the specified period. The registry record defines serious adverse events by outcomes or significance, including death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly or birth defect, or another event considered significant by the investigator.

This endpoint is used to capture serious safety events rather than all reported adverse events. A seriousness criterion and an investigator’s judgment about relatedness both contribute to whether an event is included in this measure. Consequently, the endpoint does not represent the total number of adverse events, nor does it count events considered unrelated to study drug. The endpoint is reported separately for each intervention group.

For this record, every listed group has a posted value of 0.0 participants for the primary endpoint. That is the observed count for the specified endpoint and timeframe. It does not imply that no other adverse events occurred: the separate adverse-event information lists participants with other adverse events in each group. The endpoint also cannot answer questions about pharmacokinetics, bone mineral density, P1NP, or antibodies; those are separate secondary outcomes, and their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports counts of participants, rather than a continuous measurement, for the primary endpoint. Each participant either met the endpoint definition during Day 1 through Day 85 or did not. The posted outcome is the number meeting that definition in each group. This makes the result straightforward to describe, but interpretation still depends on the endpoint definition, the number of participants observed, and whether a formal comparison was performed.

What does the count represent?

The outcome is the number of participants with one or more qualifying serious adverse events considered related to study drug. It is not a count of all individual serious events: a participant with multiple qualifying events would still be represented as one participant for this endpoint. The record specifies that the investigator judged whether an SAE was related to study drug. Such attribution is part of the endpoint definition and should not be mistaken for an independently established causal relationship.

The record lists a value of 0.0 for every group. These zero counts mean that no participant in the posted group results was counted as meeting the defined endpoint. They do not imply certainty about the underlying event probability. General statistical explanation: the observed count is a sample result, and a limited number of observed participants may not reveal very rare outcomes. Greater precision generally requires more information, but no interval estimates are posted to quantify precision for these counts.

Why is a two-arm comparison unavailable?

The record does not provide an estimable two-arm comparison for this binary endpoint. As a result, there is no posted effect estimate, confidence interval, or p-value for a comparison between a LY2541546 group and placebo. The absence of a comparison is important: separate group counts alone do not supply a formal test of whether groups differ. With zero recorded primary events in every group, the posted values also contain no observed separation on this endpoint, but that does not demonstrate equivalence or rule out differences in underlying risk.

General statistical explanation: a confidence interval describes a range of values compatible with the data under a specified statistical method. It communicates uncertainty around an estimate; it does not guarantee that the true value lies in that range. A p-value, when calculated for a defined test, measures how unusual the data would be under a specified null model. Neither quantity is posted for the primary endpoint, so there is no basis to describe statistical significance or precision using those measures.

How should the group sizes be read?

The registry lists 6.0 participants in each LY2541546 group and 12.0 in the placebo group for the primary outcome. These are the denominators attached to the posted group counts. The primary endpoint population is described as all participants who received study drug. The record does not give further detail about exclusions, missing outcome assessments, or whether all participants were observed for the complete endpoint timeframe.

The trial was randomized and parallel group, but details of assignment across the multiple dose groups are not reported in the registry record. The overall masking designation is double, while the 225 mg and 750 mg intravenous groups are specifically labeled open label. The implications of these design features for the endpoint assessment cannot be fully evaluated from the record alone.

What do the planning illustrations mean?

No two-arm planning values are available for this endpoint because a comparison is not estimable from the posted results. General statistical explanation: sample-size calculations describe how many participants might be needed under stated assumptions to detect a specified effect with a chosen power and significance level. They are planning illustrations, not observed power and not evidence that a study was adequately powered. Any assumptions about the trial’s own sample-size justification or design calculations are not reported in the registry record.

Why can event-count models matter?

General statistical explanation: for count outcomes with more variability than a basic model expects, over-dispersion can make standard errors too small and uncertainty appear understated. That consideration is not directly addressed by this endpoint’s posted participant counts, which reduce the primary outcome to whether each participant had at least one qualifying event. No model for repeated event counts or over-dispersion is reported in the registry record. The record also does not specify the statistical methods used for the listed secondary outcomes or any adjustment for multiple testing.

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("7.5 mg LY2541546 - IV", "25 mg LY2541546 - IV", "75 mg LY2541546 - IV", "225 mg LY2541546 - IV", "750 mg LY2541546 - IV", "150 mg LY2541546 - SC")
n      <- c(6, 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  7.5 mg LY2541546 - IV  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  25 mg LY2541546 - IV  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  75 mg LY2541546 - IV  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  225 mg LY2541546 - IV  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  750 mg LY2541546 - IV  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  150 mg LY2541546 - 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 record lists one primary safety endpoint and four secondary outcomes: LY2541546 area under the concentration curve from time zero to infinity, change from baseline in lumbar spine bone mineral density, percent change from baseline in P1NP, and the number of participants with anti-LY2541546 antibodies. Numerical results for these secondary outcomes are not reported in the registry record. The record also does not report a multiplicity strategy, such as an ordering of tests or an adjustment to account for assessing multiple outcomes. Therefore, the relationship between any secondary-outcome analyses and a confirmatory interpretation cannot be evaluated from the posted information.

The primary endpoint population is described as all participants who received study drug. The record does not report a separate intention-to-treat population or provide further analysis-population definitions for the secondary outcomes. It also does not describe how missing observations were handled, whether any participants discontinued or had incomplete follow-up, or how missing outcome measurements were treated. These details are not reported in the registry record.

No statistical analyses are posted for the results available for this endpoint, and a two-arm comparison is not estimable. Consequently, there are no reported p-values or interval estimates to assess for multiplicity or missing-data sensitivity. The absence of these details limits assessment of how outcomes were analyzed; it does not establish that no analyses or procedures were performed outside the information in the registry record.

General statistical explanation: multiplicity can increase the chance of a false-positive finding when many hypotheses are tested, while missing-data methods can affect estimates when outcomes are not observed for every participant. These are considerations for interpreting the design and analysis. The registry record does not report enough detail to determine how either issue was handled for this study.

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 result is 0.0 participants with one or more serious adverse events considered by the investigator to be related to study drug in every listed group. The reported group sizes are 6.0 for each LY2541546 group and 12.0 for placebo. The endpoint timeframe is Day 1 through Day 85, and the primary population includes all participants who received study drug.

These are observed counts, not proof that serious related events are impossible. The endpoint is narrower than all serious adverse events because the investigator also had to consider the event related to study drug. The record does not show event-level descriptions or report a formal comparison. Death counts are not reported in the registry record.

The adverse-event information separately reports participants with other adverse events: 5 in the 7.5 mg intravenous group, 6 in the 25 mg intravenous group, 4 in the 75 mg intravenous group, 4 in the 225 mg intravenous group, 4 in the 750 mg intravenous group, 5 in the 150 mg subcutaneous group, 7 in placebo, 6 in the open-label 225 mg intravenous group, and 5 in the open-label 750 mg intravenous group. Those counts are distinct from the primary serious-event endpoint. The record does not provide enough detail to characterize the specific other adverse events from these figures alone.

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

The posted result establishes what was recorded for the defined primary endpoint in this study: every group had a value of 0.0 participants with at least one serious adverse event considered related to study drug during Day 1 through Day 85. This is a descriptive finding for the participants and observation period in the registry record. It is not a guarantee about future use, other populations, or other durations.

Because the study enrolled 60 participants across multiple intervention groups, the group counts are small. General statistical explanation: when few participants are observed, even a zero-event result can leave considerable uncertainty about the underlying probability of an event. Without a reported confidence interval or other uncertainty estimate, the precision of the group-specific event rates cannot be quantified from the posted results. No formal comparison between a treatment group and placebo is reported, so the counts do not establish that the groups are equivalent or different.

The primary measure captures serious adverse events judged related to study drug, not all adverse events. Other adverse events were reported in each group, so the zero primary endpoint counts should not be read as zero adverse experiences overall. The available counts do not describe the nature, timing, severity, or outcome of those other events.

The study’s stated objectives included pharmacokinetics and pharmacodynamics, but the numerical results for the four listed secondary outcomes are not reported in the registry record. Accordingly, the primary safety result cannot establish how LY2541546 behaved in the bloodstream, whether the listed bone mineral density or P1NP measures changed, or whether antibodies were detected. It also cannot support conclusions about efficacy, since the primary endpoint is a safety measure and no efficacy outcome is listed among the posted results summarized for this analysis.

The appropriate interpretation is therefore limited: no participant was counted for the primary related-SAE endpoint in any posted group during the stated timeframe. The record does not provide enough information to extend that observation to broader safety conclusions or to compare doses statistically.

14. Why This Trial Matters Statistically

This study illustrates how a simple safety count can be clear to describe while remaining limited in what it can establish. The primary outcome is a participant-level indicator: whether anyone had one or more serious adverse events considered related to study drug within the specified timeframe. Each group has a zero count, but the number of participants in each group is small, and no interval estimates or comparative analyses are posted.

That combination highlights an important distinction in biostatistics: an observed result is not the same as a precise estimate of an underlying rate. Zero observed events can be clinically notable, but a small set of observations cannot by itself show that the true probability is zero. Readers need both the event counts and an understanding of how much information supports them. In this record, the group counts are available, while formal precision and between-group inference are not.

The study also has multiple dose groups, two routes of administration, placebo, and designated open-label groups. Those features make it especially important to distinguish descriptive group results from a planned comparison. The registry record does not report an estimable two-arm comparison for the primary endpoint, so the results should not be converted into claims about relative risk or statistical significance.

Finally, the record lists several secondary pharmacokinetic, pharmacodynamic, and immunogenicity outcomes without numerical results. This illustrates why a study’s stated objectives and its posted result set are not interchangeable: only conclusions supported by the recorded outcome data can be drawn. The available primary counts contribute a focused description of one safety measure, not a complete account of all outcomes the study set out to assess.

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 counts are based on relatively small posted groups: 6.0 participants in each LY2541546 group and 12.0 in placebo. With no recorded primary events, the data offer limited information for estimating the frequency of rare serious events. The registry record provides no confidence intervals or other uncertainty measures for the group results.

The endpoint depends on investigator judgment about whether an SAE was related to study drug. Event-level descriptions and the reasoning behind relatedness assessments are not reported in the registry record. The counts therefore cannot be independently reviewed for event classification using the information available for this endpoint.

Although the study is listed as randomized and double masked, two groups are designated open label. The record does not explain the masking procedures or allocation process across groups. It also does not provide details on withdrawals, completeness of follow-up, missing observations, or handling of missing data. The primary population is stated as participants who received study drug, but further analysis-population definitions are not reported.

No formal two-arm comparison is available for the primary endpoint, and the numerical results for the listed secondary outcomes are not reported in the registry record. The record also does not report multiplicity handling, statistical methods for the secondary outcomes, or the study’s sample-size justification. These omissions prevent assessment of comparative inference, the precision of secondary findings, or the rationale for the enrolled group sizes.

The participants were healthy postmenopausal women and received single doses. The record does not support extending the observed counts to other populations, dosing schedules, routes beyond those studied, or longer observation periods. These limitations concern the scope and interpretability of the posted results, not whether the study was conducted appropriately.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY2541546 in Healthy Postmenopausal Women — NCT01742078.
• Registry record last updated 2019-01-23; status last verified 2018-08.
• Results first posted 2019-01-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed, randomized, parallel-group Phase 1 single-dose study of LY2541546 in healthy postmenopausal women, with enrollment of 60. It lists intravenous doses of 7.5 mg, 25 mg, 75 mg, 225 mg, and 750 mg, a 150 mg subcutaneous dose, placebo, and open-label 225 mg and 750 mg intravenous groups.

The primary endpoint was the number of participants with one or more serious adverse events considered related to study drug administration from Day 1 through Day 85. The posted value is 0.0 in each listed group. Other adverse events are reported separately, and the record lists four secondary pharmacokinetic, pharmacodynamic, and immunogenicity outcomes.

No two-arm comparison is estimable for the primary endpoint. Numerical results for the secondary outcomes, confidence intervals, p-values, missing-data methods, and multiplicity procedures are not reported in the registry record. The primary result is therefore a descriptive set of serious related-event counts rather than a formal comparison across groups.