This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of LY2216684 in Participants With Impaired Hepatic Function (NCT01241435), a na phase 1 study. The primary outcome is Pharmacokinetics: Area Under the Concentration Curve (AUC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01241435 |
| Phase | Phase 1 |
| Condition | Depressive Disorder, Major |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants with normal hepatic function or mild, moderate, or severe hepatic impairment. The primary endpoint population is participants who received at least one dose of study drug.
Intervention
A single oral dose of 18 milligrams of LY2216684, administered as 2 tablets.
Comparator
The registry record describes hepatic-function groups rather than a randomized control comparison. Participants with normal hepatic function provide a reference group for considering exposure across the impairment categories, but allocation is listed as NA.
Primary question
How does hepatic function relate to LY2216684 exposure, measured by the area under the plasma concentration curve from 0 hours to infinity? The study also collected information about side effects.
The central statistical question is whether the pharmacokinetic profile differs across the listed hepatic-function categories after the same stated dose. This is a descriptive comparison among groups in an open-label, single-group study, not a randomized estimate of a treatment effect. The registry record does not report the AUC values, group comparisons, uncertainty estimates, or a statistical test for differences. It therefore does not establish the size or precision of any relationship between hepatic function and exposure.
3. Trial Design
This completed Phase 1 study evaluated the effect of impaired hepatic function on the pharmacokinetics of LY2216684. The registry lists an enrollment of 36 and describes participants with normal hepatic function, mild hepatic impairment (Child-Pugh A), moderate hepatic impairment (Child-Pugh B), or severe hepatic impairment (Child-Pugh C). The arm descriptions list 12 participants in the normal hepatic function group and 8 in each impairment group. The study is classified as open-label, with no masking, NA allocation, and a single-group model. These classifications do not describe a randomized, masked comparison.
Participants received a single oral dose of 18 milligrams, administered as 2 tablets. The brief summary describes participation as approximately 12 days, not including screening, with a clinic confinement of 5 days/4 nights followed by an outpatient follow-up visit. Screening was required within 30 days before the start of the study. The registry lists the start as 2010-10 and primary completion as 2011-04, with status completed.
The design focuses on pharmacokinetics across hepatic-function categories. The normal-function group can serve as a descriptive reference, but the record does not identify a randomized control arm or report an adjusted comparison plan. A sample-size justification, details of the allocation process, and a statistical analysis plan are not reported in the registry record. The listed enrollment should not be interpreted as evidence of adequate precision for every group or endpoint.
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.
Overall Study
| Stage | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|
| STARTED | 12 | 8 | 8 | 8 |
| Received at Least 1 Dose of Study Drug | 12 | 8 | 8 | 8 |
| COMPLETED | 12 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: 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: Participants who received at least one dose of study drug.
| Characteristic | Unit | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 12 | 8 | 8 | 8 | 36 | |
| Age, Continuous | years | 49.5 (SD 6.3) | 55.0 (SD 4.9) | 54.5 (SD 5.6) | 51.4 (SD 6.9) | 52.3 (SD 6.2) |
| Sex: Female, Male: Female | Participants | 4 | 3 | 2 | 1 | 10 |
| Sex: Female, Male: Male | Participants | 8 | 5 | 6 | 7 | 26 |
| Race/Ethnicity, Customized: White | Participants | 10 | 8 | 8 | 8 | 34 |
| Race/Ethnicity, Customized: Black/African American | Participants | 1 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Multiple | Participants | 1 | 0 | 0 | 0 | 1 |
| Region of Enrollment: United States | Participants | 12 | 8 | 8 | 8 | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics: Area Under the Concentration Curve (AUC), measured over Up to 72 hours after administration of study drug.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | hours times nanograms/milliliter |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the plasma concentration versus time curve for LY2216684 from 0 hours to infinity, reported in hours times nanograms/milliliter. The registry describes the endpoint as a geometric mean with geometric coefficient of variation, for participants who received at least one dose of study drug. The stated timeframe is up to 72 hours after administration.
In general, an area under a concentration-time curve represents drug exposure across time: it summarizes the concentration profile rather than relying on a single measurement. Comparing exposure across hepatic-function categories can describe how pharmacokinetics vary with the recorded level of hepatic impairment. A geometric mean is a summary suited to positive measurements that may vary multiplicatively; a geometric coefficient of variation describes relative dispersion on a multiplicative scale. These are general interpretations of the statistical summaries, not details about the calculation procedure used in this study.
The registry record does not report endpoint values, the geometric coefficients of variation, confidence intervals, or group contrasts. It also does not report how the AUC through infinity was estimated from measurements taken within the stated timeframe. Without those results and methods, the direction, magnitude, and precision of any group differences cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study question and endpoint but does not include the numerical primary outcome results. It gives no geometric mean AUC values or geometric coefficients of variation for the hepatic-function groups. It also reports no confidence intervals, p-values, or estimated contrasts. Consequently, the posted information does not show whether exposure differed across groups, how large any difference was, or how precisely it was estimated.
The design is open-label and classified as single-group, with allocation listed as NA. The hepatic-function categories are therefore best understood as groups for descriptive pharmacokinetic comparison, not as randomized treatment arms. A normal hepatic function group is included, but the record does not describe randomized assignment or a like-for-like control comparison. Differences between groups would need to be interpreted in light of this design and any unreported group characteristics; the record does not provide an adjusted analysis or enough information to assess such factors.
Interpretation of a geometric mean alone would not establish how much participants' measurements varied. The geometric coefficient of variation is relevant to that variability, and interval estimates would help indicate uncertainty around group summaries or contrasts. Neither those values nor the underlying concentration data are reported in the registry record. No recalculated comparison can therefore be described from the posted information.
The safety results list no serious adverse events as affecting participants in the hepatic-function groups. Other adverse events are listed separately, with counts varying by group. These counts are descriptive and do not establish that a particular group had a higher risk: the study is not a randomized comparison, the group sizes differ, and the record does not provide a comparative safety analysis. Deaths are not reported in the registry record.
Any planning illustrations based on an observed effect should be read as design scenarios, not as observed power or evidence that the original study was designed to achieve a particular power. The registry record does not include the endpoint results needed to interpret such scenarios numerically, nor does it report the original sample-size justification. Overall, the record supports describing the question, design, and reported safety counts, but not drawing a quantitative conclusion about the primary pharmacokinetic outcome.
9. Statistical Methods Explained
The registry lists a geometric mean and geometric coefficient of variation for the primary pharmacokinetic endpoint. It does not report the statistical analysis used to produce the endpoint summaries or any inferential comparison among hepatic-function groups. The explanations below describe general statistical concepts; they should not be read as a claim that a particular procedure was used in this study.
What does the AUC measure?
In general, the area under a concentration-time curve combines concentration measurements across time into a summary of exposure. AUC from 0 hours to infinity represents exposure over the full stated interval, rather than exposure at a single sampling time. The registry gives a timeframe of up to 72 hours after administration, but it does not describe the sampling schedule, the method for estimating the portion extending to infinity, or how missing concentration measurements were handled. Those details are not reported in the registry record.
Why report a geometric mean?
In general, geometric summaries are useful for positive measurements when variation is naturally multiplicative or when values are unevenly distributed. A geometric mean summarizes a set of positive values on a multiplicative scale. It is not the same summary as an arithmetic mean, and its interpretation should be paired with information about variability and uncertainty. The registry identifies the geometric mean as the endpoint parameter but does not report the individual measurements or a calculation method.
What does geometric coefficient of variation convey?
In general, a geometric coefficient of variation describes relative spread on a multiplicative scale. It can help readers judge whether a group mean represents measurements that cluster closely or vary more widely. It is not a confidence interval and does not, by itself, show the precision of a group comparison. The registry names this dispersion measure but does not report its values for the endpoint.
How should group comparisons be approached?
In general, comparing pharmacokinetic summaries across groups involves considering the estimated group values and the uncertainty around their contrasts. An interval estimate conveys a range of values compatible with the data and model assumptions; a p-value addresses compatibility with a specified null model under those assumptions. Neither can substitute for the estimated magnitude of a difference. The registry record does not report confidence intervals, p-values, an analysis model, covariate adjustment, or a contrast definition for the primary endpoint.
The design also matters when interpreting any contrast. The registry classifies the study as single-group, open-label, with allocation listed as NA. The hepatic-function categories are not reported as randomized arms. A descriptive difference between groups would not, by itself, show that hepatic impairment caused that difference. The record does not provide details about how group characteristics were handled in analysis.
What do the planning assumptions mean?
The registry's sample-size assumptions describe planning illustrations based on the observed effect, not the study's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. These are assumptions for planning scenarios, not evidence that the completed study had a particular power. The sample-size illustrations are not observed power, and the record does not report the original sample-size justification. The primary endpoint effect itself is not reported in the registry record, so no numerical planning result can be interpreted from the record alone.
The registry lists no analyses. It therefore does not identify whether the published endpoint summaries arose from a prespecified model, whether any diagnostic checks were performed, or whether additional sensitivity analyses were conducted. Those methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies AUC as the primary endpoint and lists 3 outcome measures, but the other outcome measures and their analysis roles are not described in the record. It lists no analyses and does not report a multiplicity procedure. It is therefore unclear whether any adjustment or hierarchy was planned for multiple endpoints, group contrasts, or other statistical tests. The stated two-sided significance level of 0.05 belongs to the sample-size planning assumptions; the record does not establish it as the threshold for the trial's endpoint analysis.
The primary endpoint population is described as participants who received at least one dose of study drug. The record does not report a broader analysis-population definition, participant flow by endpoint, exclusions from the pharmacokinetic analysis, or reasons for any missing measurements. A missing-data strategy, including any imputation method or sensitivity analysis, is not reported in the registry record.
These omissions limit interpretation of precision and completeness. The record does not show whether every participant in each hepatic-function group contributed to the primary endpoint, whether missingness differed among groups, or whether the analysis population differed from the enrolled groups. It also does not provide enough information to judge the consequences of multiple testing. No assumptions about these procedures should be made from the endpoint label or study design alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Normal Hepatic Function | 0 | 12 | 0.0% |
| Mild Hepatic Impairment | 0 | 8 | 0.0% |
| Moderate Hepatic Impairment | 0 | 8 | 0.0% |
| Severe Hepatic Impairment | 0 | 8 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Normal Hepatic Function | 6 of 12 |
| Mild Hepatic Impairment | 3 of 8 |
| Moderate Hepatic Impairment | 6 of 8 |
| Severe Hepatic Impairment | 5 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | 3 of 12 | 0 of 8 | 1 of 8 | 2 of 8 |
| Headache | Nervous system disorders | 0 of 12 | 1 of 8 | 1 of 8 | 2 of 8 |
| Tinnitus | Ear and labyrinth disorders | 0 of 12 | 0 of 8 | 1 of 8 | 2 of 8 |
| Nausea | Gastrointestinal disorders | 2 of 12 | 0 of 8 | 1 of 8 | 0 of 8 |
| Urinary hesitation | Renal and urinary disorders | 1 of 12 | 0 of 8 | 1 of 8 | 1 of 8 |
| Palpitations | Cardiac disorders | 0 of 12 | 0 of 8 | 0 of 8 | 2 of 8 |
| Constipation | Gastrointestinal disorders | 0 of 12 | 0 of 8 | 0 of 8 | 2 of 8 |
| Vomiting | Gastrointestinal disorders | 1 of 12 | 0 of 8 | 1 of 8 | 0 of 8 |
| Urinary tract infection | Infections and infestations | 0 of 12 | 1 of 8 | 1 of 8 | 0 of 8 |
| Somnolence | Nervous system disorders | 0 of 12 | 1 of 8 | 0 of 8 | 1 of 8 |
The registry separates serious adverse events from other adverse events. It lists zero serious adverse events affecting participants in the normal hepatic function group, the mild hepatic impairment group, the moderate hepatic impairment group, and the severe hepatic impairment group. The corresponding numbers at risk are 12, 8, 8, and 8, respectively. These are descriptive counts for the groups, not estimates from a comparative safety analysis.
For other adverse events, the record lists 6 affected among 12 at risk in the normal hepatic function group, 3 among 8 in the mild impairment group, 6 among 8 in the moderate impairment group, and 5 among 8 in the severe impairment group. These figures should be read as reported counts within each group, not as proof of a difference between groups. The study was not a randomized comparison, and the record does not report an adjusted analysis, uncertainty estimates, or a formal comparison for safety outcomes.
Deaths are not reported in the registry record; a missing death entry should not be interpreted as a reported count of zero. The record also does not include serious adverse event terms, as the serious-event terms list is empty. These summaries do not establish causation or provide a basis for medical advice.
12. What the Result Does, and Does Not, Mean
This study is relevant to the statistical question of how LY2216684 exposure is described across categories of hepatic function after a single oral dose. The endpoint is pharmacokinetic: AUC from 0 hours to infinity, summarized as a geometric mean with geometric coefficient of variation. The registry also records adverse events and describes the participant groups and study procedures. Those details establish what the study set out to examine, but they do not supply the primary outcome values.
The main interpretive boundary is that the registry record does not report the AUC results or their uncertainty. It is not possible from the record to state whether exposure was higher or lower in any impairment group, to quantify a group difference, or to judge its precision. The record also does not report a statistical comparison or model that would support an inferential conclusion. No treatment-effect claim follows from the study classification or endpoint description.
The groups were not described as randomized arms. Comparisons across normal hepatic function and the impairment categories are therefore descriptive in the information available. Such comparisons may be affected by differences among participants or by other factors, but the record does not provide enough detail to assess those possibilities or describe adjustments.
The safety counts provide a separate descriptive account. The registry lists no serious adverse events affecting participants in the listed groups and gives counts for other adverse events. It does not provide a formal comparison, confidence intervals, or a causal assessment. The death information is not reported in the registry record.
In short, the record describes a completed pharmacokinetic study, its exposure endpoint, and its safety-count format. It does not report the outcome statistics needed to characterize the magnitude or precision of exposure differences. The absence of those results in the registry record is not evidence that groups had equal exposure or that no differences occurred.
13. Why This Trial Matters Statistically
This study illustrates why a clinical research question and a statistical result are not interchangeable. The registry identifies a specific exposure measure and distinguishes groups by hepatic function, but the endpoint values and uncertainty estimates are not reported. Without those results, readers cannot assess the magnitude, direction, or precision of a difference. A clearly named endpoint is not itself evidence of a finding.
It also highlights the importance of matching interpretation to design. The record classifies the study as open-label and single-group, with allocation listed as NA. The hepatic-function categories permit descriptive comparisons, but they are not described as randomized groups. A difference among group summaries would therefore require careful interpretation and could not automatically be attributed to hepatic function alone.
The endpoint's geometric summaries matter because pharmacokinetic measurements can be described on a multiplicative scale. In general, pairing a geometric mean with a measure of relative variability helps convey the distribution more fully than a mean alone. But the registry reports neither the endpoint values nor the dispersion values, and it gives no confidence intervals or analysis details. The statistical framework is named more clearly than the numerical result.
The record also demonstrates why safety counts should remain descriptive when comparative analyses are absent. Counts of affected participants do not, on their own, quantify uncertainty or establish a difference between groups. Keeping serious and other adverse events distinct, and treating unreported death information as missing rather than zero, preserves that distinction.
Finally, planning calculations must be separated from evidence about the completed study. The registry describes planning assumptions for sample-size illustrations, but those are not observed power and do not explain the original enrollment decision. Because the record does not report the primary effect or original sample-size justification, it cannot support a numerical judgment about whether the study was adequately sized for its pharmacokinetic question.
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 most direct limitation of the registry record for statistical interpretation is the absence of the primary endpoint results. No group-specific AUC geometric means or geometric coefficients of variation are reported, and no contrast estimates or uncertainty intervals are included. The record therefore does not permit a quantitative assessment of exposure across the hepatic-function categories.
Important analysis details are also absent. The record does not describe the concentration-sampling schedule, the method for estimating AUC from 0 hours to infinity, the statistical model, any covariate adjustment, or the handling of missing pharmacokinetic measurements. It identifies the endpoint population as participants who received at least one dose, but does not report endpoint-specific participant flow or exclusions. A missing-data strategy and sensitivity analyses are not reported in the registry record.
The study is classified as open-label and single-group, with allocation listed as NA. The hepatic-function groups are not described as randomized, so group contrasts should not be read as randomized causal estimates. The registry does not give details that would allow readers to assess group comparability or the effect of other participant characteristics.
The record lists 3 outcome measures but does not describe the other measures or any multiplicity approach. It also lists no analyses. The sample-size assumptions describe planning illustrations, not the original study design, and the original sample-size justification is not reported in the registry record.
Safety information is limited to event counts by group. Comparative safety estimates, uncertainty intervals, and a causal assessment are not reported. Deaths are not reported in the registry record. These gaps restrict interpretation of both efficacy-related pharmacokinetic questions and safety patterns.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of LY2216684 in Participants With Impaired Hepatic Function — NCT01241435.
- Registry record last updated 2018-10-22; status last verified 2018-03.
- Results first posted 2018-10-22.
- 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.
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18. Record Summary
NCT01241435 is a completed Phase 1, open-label study of a single oral dose of 18 milligrams of LY2216684 in participants with normal hepatic function or mild, moderate, or severe hepatic impairment. The registry lists enrollment of 36, start in 2010-10, and primary completion in 2011-04. The primary endpoint is AUC from 0 hours to infinity, summarized as a geometric mean with geometric coefficient of variation, with a stated timeframe up to 72 hours after administration.
The record describes the design, endpoint, and adverse-event counts, but does not report primary pharmacokinetic results, inferential analyses, or confidence intervals. It lists no analyses. The safety summaries include no serious adverse events affecting participants in the listed groups; counts for other adverse events are reported by group. Deaths are not reported in the registry record.