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 LY3337641 in Healthy Participants (NCT03099148), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3337641.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03099148 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy participants. The primary endpoint population was all randomized participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data. The registry record reports enrollment of 29 participants; the numbers contributing to the posted endpoint summaries vary by condition.
Intervention
The study examined LY3337641 in test formulation 1 (T1) after fasting and after a high-fat meal, and in test formulation 2 (T2) after fasting. The posted descriptions specify a single oral dose of 20mg for T1 and 20 mg for T2. A reference formulation was also administered after fasting.
Comparator
The reference condition was a single oral dose of reference formulation R with water after an overnight fast. The trial also permits descriptive comparisons between the T1 and T2 formulations under fasting conditions, and between fed and fasted administration of T1. The registry record does not report a single reduced comparison for the posted results.
Primary question
The primary endpoint was maximum observed LY3337641 concentration in blood, or Cmax, measured in nanograms per milliliter. The study asked whether exposure differed across formulations and whether a high-fat meal affected exposure. It also described safety and tolerability. The registry record does not provide an inferential analysis of these questions.
3. Trial Design
This was a phase 1, randomized, open-label, crossover study of LY3337641 in healthy participants. In a crossover design, participants receive more than one study condition, so measurements can be described within the same participant across conditions as well as by condition. The registry record says participants took part in all four periods. It does not report the allocation sequence, the method used to randomize participants, or the order in which each participant received the conditions.
The four conditions were reference formulation R after fasting, LY3337641 T1 after fasting, LY3337641 T1 after a high-fat meal, and LY3337641 T2 after fasting. Each was described as a single oral dose in one of the four periods. The study summary says each period included 4 overnight stays (5 days) in the Clinical Research Unit. The expected duration was up to 8 weeks, including screening, dosing, and follow-up. The registry record lists the start date as 2017-04-04, primary completion as 2017-05-31, and status as completed.
Enrollment was 29. The Cmax summaries include 28 participants for reference R-fasted, 29 for T1-fasted, 27 for T1-fed, and 27 for T2-fasted. The registry record does not explain these differences in endpoint counts. It identifies the primary endpoint population as randomized participants who received at least 1 dose and had evaluable pharmacokinetic data. The record does not report a washout interval, period-specific sequence details, or how possible period or carryover effects were handled.
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.
Period 1
| Stage | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| STARTED | 7 | 7 | 7 | 8 |
| Received at Least 1 Dose of Study Drug | 7 | 7 | 7 | 8 |
| COMPLETED | 7 | 7 | 7 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Wash-out
| Stage | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| STARTED | 7 | 7 | 7 | 8 |
| COMPLETED | 7 | 6 | 7 | 8 |
| NOT COMPLETED | 0 | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| scheduling conflict | 0 | 1 | 0 | 0 |
Period 2
| Stage | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| STARTED | 7 | 6 | 7 | 8 |
| COMPLETED | 7 | 6 | 7 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Wash-out
| Stage | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| STARTED | 7 | 6 | 7 | 8 |
| COMPLETED | 7 | 5 | 7 | 8 |
| NOT COMPLETED | 0 | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Sequence ADBC | Sequence BACD | Sequence CBDA | Sequence DCAB |
|---|---|---|---|---|
| Adverse Event | 0 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study drug and had evaluable 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.
| Characteristic | Unit | Overall |
|---|---|---|
| Participants analysed | 29 | |
| Age, Continuous | years | 38 (SD 7.6) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 28 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 29 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 29 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Singapore | Participants | 29 |
| Body Mass Index (BMI) | kilograms per meter squared | 25.53 (SD 2.69) |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3337641, measured over Period 1,2,3,4 (Day 1): Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 36, 48 and 72 hours postdose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nanograms per milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was pharmacokinetic Cmax: the maximum observed concentration of LY3337641 in blood, reported in nanograms per milliliter. Concentrations were scheduled from predose through 72 hours postdose, with measurements at the time points listed in the registry record for Period 1,2,3,4 (Day 1). Cmax represents the highest observed concentration among the measurements collected for an individual under a study condition. It is used in pharmacokinetic research to describe peak exposure, which can differ across formulations or with food.
The registry reports a geometric mean and geometric coefficient of variation for each condition. A geometric mean is a way of summarizing positive measurements when their distribution is better represented on a logarithmic scale than on an ordinary scale. The geometric coefficient of variation describes relative spread around that geometric mean; it is not a confidence interval and does not by itself indicate how precisely a comparison has been estimated.
The Cmax endpoint can describe peak concentration, but it does not alone describe total exposure over time or establish the clinical importance of any difference. The registry record does not report an inferential comparison, confidence intervals, or a threshold for interpreting the size of a Cmax difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted Cmax geometric means were 66.7 ng/mL for reference formulation R-fasted, 64.9 ng/mL for T1-fasted, 56.8 ng/mL for T1-fed, and 65.5 ng/mL for T2-fasted. The corresponding geometric coefficients of variation were 40.0, 41.0, 44.0, and 35.0. These are descriptive summaries for the four study conditions, not estimates from a reported adjusted comparison.
The group counts attached to those results were 28 for R-fasted, 29 for T1-fasted, 27 for T1-fed, and 27 for T2-fasted. They are endpoint summary counts, not a replacement for the enrollment figure or a statement about why a participant may not appear in a particular condition's summary. The registry record does not report the reasons for the differences in these counts.
The values allow a descriptive reading of peak concentration under each condition. However, the registry record lists no analyses for the posted primary results and gives no confidence limits, p-values, or model-based estimates. It therefore does not establish whether any observed separation between condition summaries is distinguishable from sampling variation. Nor does the record report a prespecified margin for deciding whether concentrations are sufficiently similar for a particular purpose. The displayed geometric coefficients of variation describe variability, but they do not supply the uncertainty around a contrast.
The crossover design means the conditions were studied in participants who took part across periods, which can make within-participant comparisons relevant. But the posted summaries are condition-level geometric means; the registry record does not give paired contrasts or the covariance information needed to assess the precision of such contrasts. It also does not report how period effects, sequence effects, or carryover were considered in analysis.
Accordingly, the posted results support statements about the observed Cmax summaries and their reported spread in this study. They do not, by themselves, establish the size or precision of a treatment contrast, a food effect, or a formulation effect. The record also reports adverse-event counts, which should be read as descriptive safety observations rather than as a comparative safety analysis.
9. Statistical Methods Explained
The registry presents a geometric mean for Cmax in each condition, accompanied by a geometric coefficient of variation. These are summary statistics for pharmacokinetic measurements. They provide a way to describe typical concentration and variation when values are positive and may be unevenly distributed. This is a general statistical explanation of the summaries, not a claim about the distribution of individual measurements in this study.
What does the geometric mean represent?
In general, the geometric mean summarizes values on a multiplicative scale. It is often useful for concentration measurements because a proportional change can be more informative than an equal absolute change across the range of values. A geometric mean is not the same as an arithmetic average. The registry record does not report individual participant values, so the geometric means cannot be used to reconstruct the data distribution or identify unusually high or low observations.
How should the geometric coefficient of variation be read?
In general, a coefficient of variation expresses spread relative to a mean. A geometric coefficient of variation is associated with summaries on the log scale and describes relative variability in the measurements. The reported values are 40.0 for R-fasted, 41.0 for T1-fasted, 44.0 for T1-fed, and 35.0 for T2-fasted. These quantities do not show the uncertainty in a difference between conditions. They are also not confidence intervals, and they should not be interpreted as the proportion of participants whose measurements fall within a particular range.
Why is Cmax a pharmacokinetic endpoint?
As a general concept, Cmax is the highest observed concentration among scheduled samples after dosing. It is a measure of peak exposure. The registry lists measurements from predose through 72 hours postdose and identifies the maximum observed drug concentration as the endpoint. Since sampling occurs at specified times, the observed maximum is based on those measurements; the registry does not describe a method for estimating a concentration peak between sampling times. Cmax is distinct from a measure that summarizes exposure over the full concentration-time profile.
What can a crossover design contribute?
In general, a crossover design measures participants under multiple conditions. Because a participant can serve as their own reference, comparisons may account for some stable differences between people. The design also requires attention to period, sequence, and possible carryover effects. The registry record states that participants took part in all four periods, but it does not report the condition sequence, washout details, or an analysis model addressing these design features. The condition-level summaries alone do not reveal whether a paired analysis was performed.
What does inferential precision require?
In general, a confidence interval describes a range of values compatible with an estimated effect under a specified statistical method and assumptions. A p-value addresses evidence against a defined null hypothesis under a model; it does not measure the size or clinical importance of an effect. The registry record does not post confidence intervals, p-values, or estimates for contrasts between conditions. Consequently, the posted Cmax means and their coefficients of variation cannot answer how precisely the differences between conditions were estimated.
How should planning calculations be distinguished from trial results?
In general, sample-size calculations are planning illustrations based on assumptions about an effect, variability, allocation, and statistical method. They are not observed outcomes and should not be described as observed power. The registry record describes a planning approach based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report the trial's own sample-size justification. Any planning illustration should therefore be kept separate from the completed trial's observed Cmax summaries and should not be treated as evidence that a particular contrast was adequately powered.
The record identifies the primary analysis population as all randomized participants who received at least 1 dose and had evaluable PK data. It does not provide a fuller statistical analysis plan, a definition of evaluability beyond that description, or methods for handling missing measurements. These omissions limit the ability to reproduce or assess an inferential analysis from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study addressed more than one pharmacokinetic question: relative bioavailability across formulations and the effect of a high-fat meal on LY3337641 exposure. It also described safety and tolerability. When several outcomes or contrasts are examined, multiplicity can increase the chance of a chance finding if each is tested separately. In general, statistical plans can address this through prespecified outcome hierarchies or adjustment procedures. The registry record does not report a multiplicity strategy, a hierarchy of contrasts, or inferential tests for the posted primary results.
The registry lists the primary Cmax endpoint and identifies its analysis population as randomized participants who received at least 1 dose and had evaluable PK data. No secondary results are posted in the registry record. The record does not explain how missing or nonevaluable pharmacokinetic measurements were handled, whether any imputation was used, or whether exclusions occurred after randomization. The differing condition-level endpoint counts are reported, but the reasons are not reported in the registry record.
In general, missing-data handling matters because estimates may depend on which measurements are available and why other measurements are absent. A crossover study can also have incomplete condition sequences for some participants, so the analysis population and the handling of partial data are relevant to interpretation. The registry record does not describe whether participants with incomplete period data contributed to any analysis or how within-participant dependence was addressed.
The record does not report an interim analysis plan or a detailed statistical analysis plan. These matters should therefore be treated as unreported, rather than inferred from the design or from the numerical summaries.
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 |
|---|---|---|---|
| Reference Formulation (R-fasted) | 0 | 28 | 0.0% |
| LY3337641 (T1-fasted) | 0 | 29 | 0.0% |
| LY3337641 (T1-fed) | 0 | 27 | 0.0% |
| LY3337641 (T2-fasted) | 0 | 27 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Reference Formulation (R-fasted) | 0 of 28 |
| LY3337641 (T1-fasted) | 0 of 29 |
| LY3337641 (T1-fed) | 0 of 27 |
| LY3337641 (T2-fasted) | 0 of 27 |
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 |
|---|---|
| Reference Formulation (R-fasted) | 6 of 28 |
| LY3337641 (T1-fasted) | 4 of 29 |
| LY3337641 (T1-fed) | 5 of 27 |
| LY3337641 (T2-fasted) | 2 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Reference Formulation (R-fasted) | LY3337641 (T1-fasted) | LY3337641 (T1-fed) | LY3337641 (T2-fasted) |
|---|---|---|---|---|---|
| Catheter site swelling | General disorders | 1 of 28 | 2 of 29 | 2 of 27 | 1 of 27 |
| Catheter site bruise | General disorders | 1 of 28 | 1 of 29 | 3 of 27 | 0 of 27 |
| Catheter site erythema | General disorders | 1 of 28 | 2 of 29 | 1 of 27 | 1 of 27 |
| Headache | Nervous system disorders | 2 of 28 | 0 of 29 | 0 of 27 | 0 of 27 |
| Erythema | Skin and subcutaneous tissue disorders | 2 of 28 | 0 of 29 | 0 of 27 | 0 of 27 |
The registry reports serious adverse events as zero in each condition: R-fasted, T1-fasted, T1-fed, and T2-fasted. The corresponding numbers at risk were 28, 29, 27, and 27. Deaths were also reported as zero in each condition. These are the serious-event and death counts posted for the study conditions; they do not establish that no non-serious events occurred.
Other adverse events were reported in the registry as counts of 6 for R-fasted, 4 for T1-fasted, 5 for T1-fed, and 2 for T2-fasted. The corresponding numbers at risk were 28, 29, 27, and 27. These are counts, not percentages or adjusted comparisons. The record does not provide a statistical comparison of these counts, event-level timing, or a breakdown of serious-event terms. The list of top serious adverse event terms is empty.
In general, adverse-event counts in a small study describe what was recorded during the study conditions, but they do not by themselves establish comparative risk. Differences in exposure time, event definitions, or reporting can matter when interpreting counts. The registry record does not report enough detail to assess those factors or to make a comparative safety estimate. The results should therefore be read as descriptive safety reporting within this study.
12. What the Result Does, and Does Not, Mean
The results describe a phase 1 pharmacokinetic study in healthy participants. The registry reports Cmax geometric means and geometric coefficients of variation for the reference formulation after fasting, T1 after fasting, T1 after a high-fat meal, and T2 after fasting. This provides a descriptive account of peak concentrations observed under those conditions. The record also reports adverse-event counts, serious adverse events, and deaths.
These findings do not establish that one formulation is equivalent or superior to another, or that food has a particular effect of a specified size. Such conclusions would require a defined comparison and an estimate of its uncertainty, and potentially a prespecified equivalence or bioavailability criterion. The registry record does not provide those inferential results or criteria. A difference between descriptive means, by itself, is not a statistical test.
The study was conducted in healthy participants and used single-dose conditions. Its results therefore describe the study setting and the posted endpoint population, rather than outcomes in a broader patient population or under a different dosing pattern. The registry record does not report evidence about clinical benefit, longer-term outcomes, or effectiveness in a disease population. Cmax describes peak concentration and does not represent every aspect of pharmacokinetic exposure.
The reported absence of serious adverse events and deaths in the condition summaries is a description of events recorded in this study. It is not proof that such events cannot occur, nor does it establish a safety difference between conditions. The posted counts of other adverse events are also descriptive and are not accompanied by comparative statistical estimates.
The appropriate interpretation is therefore bounded: the record documents the design, the condition-specific Cmax summaries, and adverse-event counts. It does not report the analysis needed to quantify comparative effects or their precision. No clinical recommendation follows from these registry results alone.
13. Why This Trial Matters Statistically
This trial illustrates how pharmacokinetic questions can be studied with a crossover design. The same participants took part in all four periods, and the conditions varied by formulation and feeding status. In general, this structure can make within-participant comparisons useful because stable individual differences may be less influential than in a design where each person receives only one condition. At the same time, interpretation depends on the period sequence, adequate separation between conditions, and an analysis that accounts for repeated measurements. Those details are not reported in the registry record.
The study also shows why endpoint summaries and treatment comparisons are not interchangeable. Condition-specific geometric means and coefficients of variation describe the observed measurements, but they do not quantify uncertainty in a contrast. For a comparative pharmacokinetic question, paired estimates and confidence intervals would help readers assess both the size and precision of the contrast. The registry record does not report these inferential results.
There is also a useful distinction between peak concentration and broader exposure. Cmax describes the maximum observed concentration, while other pharmacokinetic measures can address different features of the concentration-time profile. A result for Cmax should not be treated as a complete characterization of exposure or as a clinical outcome.
Finally, the study demonstrates the importance of transparent reporting around analysis populations, missing data, multiplicity, and safety. The registry gives condition-level counts and an endpoint population definition, but does not explain the differences in counts or detail the statistical handling of the repeated measurements. These reporting details are central to judging how much weight to place on descriptive results.
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 registry record does not report inferential comparisons for the primary Cmax endpoint. It gives condition-specific geometric means and coefficients of variation, but no confidence intervals, p-values, or model-based contrast estimates. As a result, the precision of differences between formulations or feeding conditions cannot be assessed from the posted results.
The record does not describe the randomization sequence, condition order, washout interval, or how period and carryover effects were addressed. These are relevant features of a crossover study. It also does not explain why the endpoint counts differ across conditions or describe handling of missing and nonevaluable measurements beyond defining the primary analysis population.
The trial enrolled healthy participants and used single-dose administration. The posted results therefore have a limited setting and do not address outcomes in a patient population, repeated dosing, or clinical effectiveness. The registry record does not report longer-term outcomes or a clinical endpoint.
The endpoint is maximum observed concentration, based on scheduled sampling through 72 hours. It does not by itself describe the full concentration-time profile. The registry record does not report a criterion for deciding whether a formulation comparison meets a bioavailability standard, nor does it post a statistical plan explaining how multiple questions or contrasts were handled.
Safety reporting is also descriptive. The registry provides event counts by condition but no comparative analysis, and the list of top serious adverse event terms is empty. These limitations concern what can be concluded from the registry record; they do not establish that an unreported method or analysis was absent from other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of LY3337641 in Healthy Participants — NCT03099148.
- Registry record last updated 2023-10-17; status last verified 2023-10.
- Results first posted 2023-10-17.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT03099148 is a completed phase 1 randomized, open-label crossover study sponsored by Eli Lilly and Company. Its title is A Study of LY3337641 in Healthy Participants, and its official title describes relative bioavailability and the effect of food on bioavailability. The registry lists enrollment of 29, with a start date of 2017-04-04 and primary completion on 2017-05-31.
Participants took part in four periods involving reference formulation R-fasted, LY3337641 T1-fasted, T1-fed, and T2-fasted conditions. The primary endpoint was maximum observed drug concentration, summarized by geometric mean and geometric coefficient of variation. The posted results give condition-specific Cmax summaries and adverse-event counts. The registry record does not report inferential comparisons, confidence intervals, a detailed statistical analysis plan, or explanations for the differing endpoint counts.