A Study of the Effect of LY2189265 on Two Blood Pressure Drugs: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Effect of LY2189265 on Two Blood Pressure Drugs (NCT01324388), a randomized phase 1 study. The primary outcome is Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril.

2. Clinical Question

The study had two related but distinct aims. In Part 1, the pharmacokinetic question concerned lisinopril exposure among participants with hypertension who were already taking lisinopril. In Part 2, the focus shifted to metoprolol pharmacokinetics and to heart rate and blood pressure when LY2189265 was given with a beta-blocker. Those are not interchangeable questions: a result about lisinopril exposure would not, by itself, answer questions about metoprolol exposure or cardiovascular measurements.

The record lists type 2 diabetes mellitus as a condition, while its study summary describes the Part 1 population as participants with hypertension taking lisinopril and the Part 2 population as healthy volunteers. The registry's primary endpoint population is further restricted to participants who received study drug and had evaluable lisinopril AUC data. The record does not provide endpoint estimates that would show how the observed lisinopril exposure compared across the Part 1 groups.

3. Trial Design

The registry identifies this as a randomized, single-masked, parallel phase 1 study, with enrollment of 51. It was completed, with a start date of 2011-03 and primary completion in 2011-08. The registry summary divides the investigation into two parts with different populations and objectives, so the overall design label does not capture every detail of the treatment schedule.

Part 1 studied LY2189265 alongside established lisinopril therapy in participants with hypertension. The intervention arms were LY2189265 plus lisinopril and placebo plus lisinopril. The LY2189265 or placebo injections were scheduled on Days 1, 8, 15, and 22; lisinopril continued daily at the participant's prescribed dose. The primary endpoint focused on lisinopril AUC at Day -1, Day 3, and Day 24.

Part 2 concerned healthy subjects and included treatment sequences involving LY2189265 and metoprolol. The summary describes a crossover design, with a single LY2189265 injection in one period and a period involving seven daily doses of metoprolol plus a single LY2189265 injection. The arm descriptions identify a washout period of at least 21 days between treatment periods. The registry's overall model is listed as parallel, while the Part 2 description specifically calls that part a crossover; readers should keep the part-specific description in view rather than assuming every feature applies uniformly.

The listed secondary outcomes include 24-hour mean heart rate and blood pressure in response to LY2189265 with lisinopril, and metoprolol AUC and maximum concentration with LY2189265. The registry record does not report a detailed statistical analysis plan, allocation ratios, or the rationale for the enrollment target.

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.

Part 1 of Study

Reasons for not completing this period:

Part 2 of Study: First Intervention

Reasons for not completing this period:

Part 2: Washout of at Least 21 Days

Part 2 of Study: Second Intervention

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of study drug (LY2189265 or placebo) with evaluable lisinopril AUC 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: Participants who received at least one dose of study drug (LY2189265, placebo, or metoprolol).

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril, measured over Day -1, Day 3, Day 24 of Part 1.

The primary endpoint is the area under the concentration curve for lisinopril, with the unit reported as (nanograms*hours/milliliter)/milligram. AUC represents drug exposure across a period of concentration measurement: generally, it captures both the level and duration of drug concentrations rather than a single concentration reading. This makes it useful for a pharmacokinetic question about whether co-administration is associated with a change in exposure.

The registry specifies a geometric mean as the endpoint summary and a geometric coefficient of variation as its measure of dispersion. In general, geometric summaries are used for positive measurements whose distribution is asymmetric or multiplicative. A coefficient of variation describes variability relative to the scale of the measurements; the geometric version is suited to a geometric summary. These are descriptive choices and do not, on their own, establish whether groups differ statistically.

The endpoint is assessed at Day -1, Day 3, and Day 24 of Part 1. The stated analysis population consists of participants who received at least one dose of LY2189265 or placebo and had evaluable lisinopril AUC data. The record does not report the endpoint values, group estimates, uncertainty intervals, or a statistical comparison. Therefore, the endpoint definition indicates what was intended to be measured, but not what the study found about lisinopril exposure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes randomized allocation, single masking, and a parallel model for this phase 1 study. Randomization is generally intended to reduce systematic differences between treatment groups at assignment. Masking is generally intended to limit the influence of treatment knowledge on behavior, assessment, or reporting, depending on who is masked. The registry does not identify who was masked or provide further procedural details, so the exact implementation is not reported in the registry record.

The overall design description needs to be read alongside the two-part study summary. Part 1 compares LY2189265 plus lisinopril with placebo plus lisinopril for a lisinopril pharmacokinetic question. Part 2 is described as a crossover study involving sequences of LY2189265 and metoprolol. In a crossover design, participants receive treatments in more than one period, and within-participant comparisons may be relevant; in a parallel design, participants are assigned to a treatment group and comparisons are made between groups. These general distinctions help explain why Part 2 should not be interpreted as identical to Part 1. The registry record does not report details of the statistical model used for either part.

What does the AUC measure?

In general, area under the concentration curve is a pharmacokinetic measure of drug exposure over time. It summarizes a trajectory of concentration measurements rather than relying on a single observation. The primary endpoint specifies lisinopril AUC, a unit normalized by milligram, and measurements at Day -1, Day 3, and Day 24 of Part 1. Without the reported AUC estimates and their comparison, the definition alone does not reveal whether exposure differed between the study groups.

Why use a geometric summary?

The registry specifies geometric means and geometric coefficients of variation. In general, geometric summaries are appropriate for positive quantities that vary multiplicatively or are right-skewed. A geometric mean is calculated on a logarithmic scale and expressed back on the original scale. This can make a central estimate more representative when values vary proportionally. A geometric coefficient of variation describes dispersion relative to the geometric mean, rather than giving an absolute spread in the original units. These are general properties, not evidence about the distribution observed in this study; distributional details are not reported in the registry record.

What would an inferential comparison add?

In general, a contrast between treatment groups puts an estimated difference or ratio into direct relation to the study question. A confidence interval conveys uncertainty around an estimate under the chosen model, and a hypothesis test evaluates compatibility with a specified null hypothesis. The registry record does not report an estimate, interval, or test for the primary endpoint. It also does not report the analysis model, covariate adjustment, handling of repeated measurements, or criteria for selecting an analysis population beyond the endpoint population description. These details are not reported in the registry record.

How should the planning assumptions be understood?

The record describes a sample-size 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 frames the target effect as a stated fraction of the observed effect. In general, such illustrations ask how many participants per arm might be needed to detect an assumed effect under chosen assumptions. They are not observed power and do not show that the study had a particular probability of detecting its actual effect. The trial's own sample-size justification is not reported in the registry record, and the planning figures themselves are not stated in the registry record for this account.

The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. This is consequential for statistical interpretation: an analysis at one time point may answer a different question from an analysis across time points, and different outcome categories may entail different contrasts. The record does not specify a hierarchy, primary time point for inference, or a method for handling multiple comparisons. Therefore, it is not possible to infer which single test, if any, was designated as decisive.

In general, when data are collected at multiple times, repeated observations from the same participant are related rather than independent. Statistical methods may account for that dependence, but the method chosen can affect standard errors and uncertainty estimates. The registry provides the endpoint time points but does not report whether repeated measurements were modeled jointly or assessed separately. It would be inappropriate to assume a particular model from the endpoint schedule alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary lisinopril AUC endpoint and secondary measures of 24-hour heart rate, 24-hour blood pressure, metoprolol AUC, and metoprolol maximum concentration. It also states that the primary outcome has several categories or time points and was not reduced to one comparison. With multiple outcomes or time points, general statistical practice recognizes a multiplicity issue: carrying out multiple tests can increase the chance of at least one apparently unusual result under a null model. The registry record does not report a multiplicity adjustment, testing hierarchy, or prespecified approach for choosing among time points.

The record reports zero analyses and does not provide inferential results for the primary endpoint. It does not state the statistical methods for the listed secondary outcomes, or whether any analyses were adjusted for baseline values or other variables. These methods are not reported in the registry record.

The primary endpoint population is defined as participants who received at least one dose of LY2189265 or placebo and had evaluable lisinopril AUC data. This identifies the intended analysis population but does not show how many participants contributed data at each time point, how missing observations were handled, or whether exclusions differed across groups. Those details are not reported in the registry record. The record also does not describe imputation, sensitivity analyses, or the reasons for missing endpoint data.

As a general point, missing-data handling can influence an estimate when the availability of measurements is related to treatment, participant characteristics, or outcome values. Complete-case analysis, imputation, and model-based approaches rely on different assumptions. Without the analysis details and missingness information, the robustness of any endpoint estimate cannot be assessed. No specific missing-data method should be inferred from the stated endpoint population alone.

11. 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 registry reports serious adverse event counts by study group. For Part 1: LY2189265 plus lisinopril, zero serious adverse events were recorded among 23 participants at risk; for Part 1: placebo plus lisinopril, zero were recorded among 8 at risk. For Part 2: LY2189265, zero were recorded among 19 at risk; for Part 2: metoprolol, zero among 20 at risk; and for Part 2: LY2189265 plus metoprolol, zero among 19 at risk. Death counts are not reported in the registry record.

The registry also lists participants with other adverse events: 13 in Part 1: LY2189265 plus lisinopril, 1 in Part 1: placebo plus lisinopril, 7 in Part 2: LY2189265, 4 in Part 2: metoprolol, and 13 in Part 2: LY2189265 plus metoprolol. These counts are descriptive and should be read in the context of the separate study parts and treatment groups. They are not adjusted comparisons, and they do not establish why an event occurred. The registry record does not provide serious adverse event terms or additional detail about event severity, timing, or attribution.

A zero recorded serious-event count is a statement about the registry's reported count in that group, not proof that an event is impossible or that no safety uncertainty remains. The figures also do not answer the primary pharmacokinetic question.

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

The record supports a description of what the trial set out to study: lisinopril exposure during LY2189265 or placebo co-administration in Part 1, and selected pharmacokinetic and cardiovascular measures involving LY2189265 and metoprolol in Part 2. It also identifies the primary endpoint, measurement schedule, study populations as described, and treatment schedules. Those details clarify the study question and the types of data that were intended to answer it.

The record does not report the primary endpoint result or an inferential comparison. Consequently, it does not establish the size, direction, or precision of any difference in lisinopril AUC. The same limitation applies to the listed secondary outcomes: their names are present, but outcome estimates are not reported in the registry record. No conclusion about the effect of co-administration on heart rate, blood pressure, or metoprolol pharmacokinetics can be drawn from the endpoint descriptions alone.

In general, a study's design can clarify how an effect was to be estimated, but design details do not substitute for observed results. Randomization can support causal comparisons when allocation, follow-up, outcome measurement, and analysis are appropriate. The registry record does not give enough analysis detail or outcome data to evaluate those conditions fully. The phase 1 designation and enrollment describe the study context, not the certainty or clinical importance of an unreported finding.

The safety counts should likewise be interpreted narrowly. They describe the reported numbers of serious and other adverse events in the listed groups, without providing comparative statistical analyses or complete event-level context. They are not a substitute for the missing primary endpoint evidence, and they should not be read as a general assessment beyond the groups and outcomes reported.

Overall, this registry entry is useful for understanding the study's objectives and planned measurements. It does not provide enough results to quantify treatment effects or assess their statistical uncertainty. Any stronger claim about the findings would go beyond what is reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates a common distinction in clinical research between a well-defined question and a reported answer. The primary endpoint is specific: lisinopril AUC at stated Part 1 time points, summarized with a geometric mean and geometric coefficient of variation. That level of definition tells readers what kind of measurement the study intended to use. It does not, by itself, reveal the observed exposure or its uncertainty.

The trial also separates questions by population and treatment context. Part 1 concerns lisinopril in participants with hypertension; Part 2 concerns metoprolol and cardiovascular measurements in healthy subjects. Keeping those objectives distinct prevents a result from one part from being generalized to a different drug, population, or endpoint. The record's overall parallel-model label and its Part 2 crossover description also show why design labels may need to be interpreted alongside the part-specific account.

Statistically, the record highlights the importance of specifying which comparison answers the primary question when outcomes have several time points or categories. The registry says the primary outcome was not reduced to a single comparison and reports zero analyses. Without an estimate and an analysis description, neither effect magnitude nor precision can be assessed. A planning illustration based on an observed effect is not a replacement for the trial's own reported result and is not observed power.

The safety counts offer another useful distinction: descriptive event tallies are not the same as adjusted treatment comparisons, and counts from separate parts should not be collapsed into one conclusion. Clear separation of estimands, populations, measurements, and analysis methods is central to interpreting early clinical studies. In this case, the record makes the intended questions visible while leaving the outcome evidence unreported.

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 principal limitation for interpreting efficacy-related outcomes is that the registry record does not report the primary endpoint estimates, comparisons, confidence intervals, or p-values. It lists outcome measures but no analyses. As a result, the effect and its precision cannot be assessed from this record.

The primary outcome includes several categories or time points and is not reduced to one comparison. The registry does not describe a prespecified testing hierarchy, multiplicity adjustment, or analysis model. It also does not report how repeated measurements were handled. These omissions limit assessment of how any potential contrast would have been selected and estimated.

The endpoint population is defined by treatment exposure and evaluable lisinopril AUC data, but the record does not state the number with evaluable data at each time point, the extent or pattern of missingness, or how missing measurements were addressed. The registry does not report an intention-to-treat analysis or another primary analysis population beyond the stated endpoint definition. These matters are not reported in the registry record.

There is also a design-description distinction: the overall model is listed as parallel, whereas Part 2 is described as crossover. The part-specific account supplies treatment sequences and a washout period of at least 21 days, but the statistical handling of periods, sequences, or within-participant comparisons is not reported. No allocation ratio, detailed masking information, or sample-size justification is reported in the registry record.

Finally, the listed adverse-event counts are summaries without event-level terms or inferential comparisons. Death counts are not reported in the registry record. The counts should therefore be read as limited descriptive safety information, not as a complete characterization of safety or a comparison adjusted for study design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Effect of LY2189265 on Two Blood Pressure Drugs — NCT01324388.
• Registry record last updated 2014-10-08; status last verified 2014-10.
• Results first posted 2014-10-08.
• 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

NCT01324388 is a completed randomized, single-masked phase 1 study sponsored by Eli Lilly and Company. The registry reports enrollment of 51, a start date of 2011-03, and primary completion in 2011-08. Its two parts examined LY2189265 with lisinopril and LY2189265 with metoprolol.

The primary endpoint was lisinopril AUC, summarized as a geometric mean with geometric coefficient of variation, at Day -1, Day 3, and Day 24 of Part 1. The registry lists eight outcome measures and zero analyses, and notes that the primary outcome was not reduced to one comparison. Primary endpoint estimates and inferential results are not reported in the registry record.

Serious adverse event counts are reported as zero for each listed group; other adverse event counts are also recorded by group. Death counts are not reported in the registry record. The available information describes study intent and selected safety counts, but does not establish the magnitude or precision of the primary pharmacokinetic result.