A Study of LY3185643 and rGlucagon in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY3185643 and rGlucagon in Healthy Participants (NCT02951780), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon.

2. Clinical Question

The study's stated purpose was to examine how the body handles the two drugs, their effects on the body, and the safety and tolerability of LY3185643. The posted primary outcome addresses pharmacokinetics: measured drug concentrations in plasma over time. It does not by itself report every pharmacodynamic effect or establish a comparative clinical benefit. The registry lists six outcome measures, but the analysis count is zero. The primary concentration results are posted by treatment condition, without inferential comparisons or confidence intervals. Therefore, the central descriptive question is how the reported Cmax values vary across the listed dose conditions, not whether one drug or dose was statistically superior to another.

3. Trial Design

This was a Phase 1, randomized, double-masked, nine-way, single-dose crossover study in healthy participants. The registry lists enrollment of 23 and identifies Eli Lilly and Company as sponsor. The study status is completed. Its stated start date is 2016-11-01, and its primary completion date is 2017-01-24. The brief description says the study would last at least 35 days, not including screening.

The interventions were LY3185643 and rGlucagon, both administered subcutaneously. The posted treatment conditions comprise five LY3185643 doses—10 ug, 25 ug, 50 ug, 100 ug, and 200 ug—and four rGlucagon doses—10 ug, 25 ug, 50 ug, and 200 ug. The outcome summaries have different numbers of participants by condition, ranging from 19.0 to 22.0. These are condition-specific counts for the posted pharmacokinetic outcome, not a replacement for the total enrollment figure.

In general, a crossover design evaluates multiple treatment conditions in the same participants, allowing within-participant observations. Randomization concerns the assignment order or treatment sequence, while masking is intended to limit knowledge of assigned treatment. The registry does not report the actual sequence allocation, washout intervals, or how period and sequence effects were handled. Those details should not be inferred from the design label alone.

The registry record names pharmacokinetics, pharmacodynamics, safety, and tolerability as study aims. The primary outcome is Cmax for both drugs. The posted concentration summaries do not constitute a complete account of all study aims. Although six outcome measures are listed, no secondary outcome analysis count is posted. The registry record does not report a detailed protocol, sample-size justification, or full statistical analysis plan.

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: Crossover study with three periods. Each participant received up to 3 doses of study drug (rGlucagon and/or LY3185643) in a dosing day as per the dosing sequence in each period with 7 to 12 days washout period.

Only the first 6 of 9 groups are shown.

Period 1

Reasons for not completing this period:

Period 2

Reasons for not completing this period:

Period 3

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of study drug (LY3185643, rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PK data.

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 randomized participants.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon, measured over 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose.

The primary endpoint is maximum observed plasma concentration, or Cmax, for LY3185643 and rGlucagon. It is reported as a geometric mean in picograms per milliliter (pg/mL), with a geometric coefficient of variation. Measurements were scheduled at 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose. The endpoint description says Cmax was assessed for each drug.

In general, Cmax represents the highest observed concentration in the sampled concentration-time profile. It is used in pharmacokinetic studies to describe peak systemic exposure after dosing. The observed value depends on the sampling schedule: a peak occurring between scheduled measurements may not be captured directly. The registry lists the measurement times but does not report individual concentration-time profiles or the time to maximum concentration as the primary endpoint.

A geometric mean summarizes values on a multiplicative scale, which is often useful for concentration data that vary proportionally. The geometric coefficient of variation describes dispersion on that scale. These summaries describe the posted concentrations; they are not estimates of clinical benefit, pharmacodynamic response, or safety. No confidence intervals for the primary outcome are included in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish descriptive summaries from estimates of comparative effects. The registry's primary outcome is presented as a geometric mean with geometric coefficient of variation for each treatment condition. No statistical analysis results are posted. Consequently, the posted values can be read condition by condition, but there is no reported test of a dose trend or a difference between LY3185643 and rGlucagon.

What does a geometric mean describe?

In general, the arithmetic mean summarizes values by adding them and dividing by their count. A geometric mean instead summarizes positive values on a multiplicative scale, by averaging after a logarithmic transformation and returning to the original scale. This can be suitable for pharmacokinetic concentrations, where relative changes and right-skewed distributions may be important. It is not the same as the median, and it does not imply that each participant had a concentration close to the reported mean.

The registry identifies the dispersion measure as a geometric coefficient of variation. In general, this measure expresses variability in relation to the geometric mean on a multiplicative scale. It is not a confidence interval and does not by itself quantify how precisely the mean is estimated. The posted record does not give confidence intervals, standard errors, individual-level data, or the method used to estimate the reported dispersion.

Why does the crossover design matter?

In general, crossover studies collect observations from the same participants under more than one treatment condition. Within-participant comparisons can account for stable differences among participants, since each participant may contribute measurements under multiple conditions. Valid interpretation can also depend on treatment sequence, period effects, and whether effects from an earlier condition carry into a later one. The record calls the study a nine-way crossover, but does not report the treatment sequences, washout schedule, or an analysis that accounts for period or sequence. These design details and their handling are not reported in the registry record.

The condition-specific outcome counts differ. A crossover analysis may use paired or repeated-measures methods, but the registry does not say whether such a model was used, how incomplete participant profiles were treated, or whether all available measurements contributed to each estimate. The posted means should not be assumed to be adjusted for within-participant correlation or other design features.

How should precision be judged?

In general, a confidence interval gives a range of values compatible with a statistical model and the observed data, at a stated confidence level. It communicates uncertainty in an estimate, which is distinct from the spread of individual observations. No confidence intervals are posted for Cmax. The geometric coefficient of variation describes dispersion, but cannot substitute for an interval around the geometric mean. With no inferential analysis results posted, the precision of treatment contrasts cannot be assessed from the registry record.

The record includes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. In general, such calculations illustrate sample sizes under specified assumptions; they do not establish the trial's actual design rationale or show the probability that this completed trial detected an effect. They are not observed power. The registry does not report its own sample-size justification, so the illustration should not be interpreted as the trial's prespecified rationale.

What can the posted analysis support?

The primary results support a descriptive account of the reported Cmax values and their geometric coefficients of variation. They do not establish statistical significance, equivalence, or noninferiority, because no such analyses are posted. Nor do the summaries reveal individual participant responses. Six outcome measures are listed, while the posted analysis count is zero and no secondary outcome analyses are reported. The registry record does not report whether interim analyses were planned or conducted, how multiplicity was handled, or a detailed statistical analysis plan.

In general, multiplicity arises when multiple outcomes, doses, or comparisons are assessed, since repeated testing can increase the chance of at least one false-positive result. The study includes multiple treatment conditions, but there are no posted comparative tests to which an adjustment can be linked. The absence of reported adjustment is not evidence that no adjustment was used; the approach is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study lists six outcome measures, but the registry reports an analysis count of zero and no posted secondary outcome analyses. The primary endpoint is described as Cmax for both drugs. The record does not provide a detailed statistical analysis plan, so it does not report which comparisons were prespecified, how multiple doses or outcomes were handled, or whether any adjustment for multiplicity was used. It also does not report whether interim analyses were planned or conducted.

The primary outcome population is defined as randomized participants who received at least one dose and had a baseline and at least one postbaseline measurement for each dose with evaluable pharmacokinetic data for both study drugs. The condition-specific counts differ, but the registry does not explain the reasons. It does not report whether missing measurements were absent because of withdrawal, sampling, assay, or another reason. The missing-data strategy and any sensitivity analyses are not reported in the registry record.

In general, excluding participants without complete measurements can affect the interpretation of a treatment summary if the missingness is related to exposure or outcome. The record's population definition identifies which measurements qualify, but does not establish why data may be unavailable or whether the included participants differ from those not included. The posted concentration summaries should therefore be interpreted as applying to the evaluable observations described, rather than assumed to represent every randomized participant equally.

The registry does not report a protocol-level analysis population beyond the stated endpoint definition, nor does it describe adjustments for the crossover structure, period, or treatment sequence. It is not possible to determine from the record whether the analysis followed a prespecified plan or how deviations from that plan were handled.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are zero for every listed treatment condition. The numbers at risk are 20 for LY3185643 10 ug, 23 for 25 ug, 21 for 50 ug, 22 for 100 ug, and 22 for 200 ug. For rGlucagon, the corresponding numbers at risk are 21, 21, 22, and 20 across 10 ug, 25 ug, 50 ug, and 200 ug. The record also reports zero deaths in every condition.

In general, a zero count means no event of that category was recorded among the participants counted in that group; it does not demonstrate that the event cannot occur. These groups are small, and the study was conducted in healthy participants. The registry does not report a comparative analysis of serious adverse events or provide confidence intervals for the counts.

The record separately lists other adverse events affecting 3, 3, 3, 5, and 4 participants across the LY3185643 doses, and 2, 1, 2, and 2 participants across the rGlucagon doses. These counts are distinct from the serious adverse event figures and should not be conflated with them. The record does not provide event terms in the listed serious-event summary.

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

The registry's primary posted result is a set of geometric mean maximum plasma concentrations for nine drug-and-dose conditions. It describes observed pharmacokinetic concentrations in healthy participants, with geometric coefficients of variation indicating dispersion. The values vary across the listed conditions, but the record does not include inferential comparisons that quantify differences or their uncertainty.

These results do not establish that one treatment is better or worse than another. They do not establish a statistically significant dose relationship, because no dose-trend analysis or hypothesis test is posted. A descriptive pattern across dose conditions is not a substitute for a model that accounts for the crossover design and uncertainty. No confidence intervals or p-values for the primary endpoint are reported.

Cmax is a concentration endpoint, not a direct measure of clinical benefit. The study's stated aims also include pharmacodynamics, safety, and tolerability, but the posted Cmax values do not answer all of those questions. The serious adverse event count is zero in each listed condition, with zero deaths recorded; this does not prove absence of risk. The separate counts of other adverse events are small descriptive counts, not comparative safety estimates.

The study concerns healthy participants and reports single-dose treatment conditions. The findings should be understood in that setting. The registry does not report evidence from which to infer effects in patients, with repeated dosing, or in other clinical settings. Nor does it report a complete protocol or statistical analysis plan sufficient to assess every design and analytic choice.

In general, a statistical result is most informative when the estimate, uncertainty, analysis population, and method are all clear. Here, concentration estimates and condition-specific counts are available, while inferential analyses and confidence intervals are not. The record supports description of the posted observations, but conclusions about comparative effects or broader clinical implications are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the design and the endpoint need to be considered together. A nine-way crossover can generate observations across several treatment conditions within a study, while the primary endpoint reduces each concentration-time profile to its maximum observed concentration. That summary is useful for describing peak exposure, but it cannot convey the full concentration-time course or all pharmacodynamic effects.

The posted geometric means and coefficients of variation give complementary descriptive information: one locates the central concentration summary, and the other indicates dispersion on a geometric scale. However, those quantities do not answer whether differences between conditions are precisely estimated. The record has no posted confidence intervals or comparative analyses. This distinction matters because a visually or numerically different set of summaries does not alone demonstrate a statistically supported difference.

The crossover label also prompts questions about within-participant analysis, treatment order, periods, and carryover. Such issues can be important in interpreting repeated observations. The registry does not report the methods used to address them, so the design cannot be assumed to have been analyzed in a particular way. A strong interpretation depends not only on the design name, but also on the model and its assumptions.

Finally, zero serious adverse events is a descriptive finding in this study, not a guarantee of safety. The condition-specific counts and healthy-participant setting limit what can be inferred from the safety record. Taken together, the study is statistically informative as a record of pharmacokinetic summaries and event counts, while its posted analyses do not support formal comparative conclusions.

14. 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 outcome is reported as condition-specific geometric means and geometric coefficients of variation, without confidence intervals, standard errors, individual-level data, or comparative tests. Consequently, the precision of estimates and contrasts cannot be assessed from the registry record. The posted results do not report p-values or an adjusted analysis of the multiple dose conditions.

Although the study is described as a nine-way crossover, the registry does not report the treatment sequences, washout intervals, or the statistical method used to account for within-participant observations, periods, or sequence. The condition-specific sample counts differ, and the reason for that variation is not reported. The record does not describe how missing pharmacokinetic measurements were handled beyond the stated endpoint population criteria.

The study enrolled healthy participants and assessed single-dose conditions. Its posted results therefore do not establish what concentrations or safety outcomes would be observed in patients or with repeated dosing. The registry lists six outcome measures but reports no analysis count and no secondary analyses. A detailed statistical analysis plan, sample-size justification, and interim-analysis information are not reported in the registry record.

The sampling schedule is specified, but individual concentration-time profiles and time-to-peak results are not included in the primary result. Cmax summarizes the highest observed concentration among scheduled measurements, so the result does not describe the complete time course. Finally, zero serious adverse events and zero deaths are counts from this study, not proof that such events cannot occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of LY3185643 and rGlucagon in Healthy Participants — NCT02951780.
• Registry record last updated 2019-09-30; status last verified 2019-09.
• Results first posted 2019-09-30.
• 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.

18. Record Summary

NCT02951780 is a completed Phase 1 randomized, double-masked, single-dose crossover study sponsored by Eli Lilly and Company. It enrolled 23 healthy participants and assessed subcutaneous LY3185643 at 10 ug, 25 ug, 50 ug, 100 ug, and 200 ug, and subcutaneous rGlucagon at 10 ug, 25 ug, 50 ug, and 200 ug.

The primary outcome was maximum observed plasma concentration, reported as geometric mean in pg/mL with geometric coefficient of variation, using measurements from predose through 180 minutes post-dose. The registry posts condition-specific outcome summaries, but no analysis results or secondary outcome analyses. Serious adverse event counts and deaths are zero in each listed condition. Comparative estimates, confidence intervals, detailed missing-data methods, and a full statistical analysis plan are not reported in the registry record.