A Study of Cephalexin Capsules in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Cephalexin Capsules in Healthy Participants (NCT02123446), a randomized phase 1 study. The primary outcome is Pharmacokinetics: Area Under the Concentration Versus Time Curve of Cephalexin From Time Zero to Infinity [AUC(0-∞)] of Cephalexin Following a Single Dose.

2. Clinical Question

The study record describes a phase 1 randomized, open-label crossover study. Participants were assigned to one of two treatment sequences and received both preparations, one in each of two study periods. The stated purpose was to compare the preparations to determine whether they were essentially the same. For the primary pharmacokinetic outcome, the registry reports a geometric mean for each preparation, but does not report a treatment contrast, confidence interval, or bioequivalence conclusion.

The posted primary values are 19.1 hour*microgram per milliliter for the Mexico-manufactured reference preparation and 19.21 hour*microgram per milliliter for the Italy-manufactured test preparation. These descriptive values alone do not establish whether a prespecified criterion for bioequivalence was met. The bioequivalence margins and the statistical analysis used to assess them are not reported in the registry record.

3. Trial Design

This was a randomized, open-label, two-period crossover study of two single-dose oral cephalexin capsule preparations. The registry identifies it as phase 1 and lists healthy volunteers as the study condition. The record gives enrollment as 28. Participants received the reference and test preparations in separate periods, with at least 7 hours between study periods according to the study summary. The planned study duration was about 2 days for each participant, not including screening or follow-up.

The reference was cephalexin manufactured in Mexico by Eli Lilly y Compañía de México, S.A. de C.V.; the test was cephalexin manufactured in Italy by Facta Farmaceutici S.p.A. Both were given once orally in one of the study periods. The study was open-label, meaning masking was not used. The registry identifies random allocation and a crossover model, but the allocation procedure, sequence-generation details, and handling of treatment order are not reported in the registry record.

For a crossover comparison, each participant receives both treatments at different times. In general, this design can allow a treatment comparison to use information from within the same participant, while also making period and sequence effects relevant to interpretation. Those are general design considerations; the registry record does not report a model or analysis addressing them. The reported primary outcome population included participants with at least one study treatment and evaluable pharmacokinetic data. The treatment-specific result counts are 25 for the reference and 25 for the test.

The study began in 2014-04, had primary completion in 2014-05, and is listed as completed. The record lists Cmax and Tmax as secondary pharmacokinetic outcomes in addition to the primary AUC outcome. Their results are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Period 1 (7 Days)

Washout Period (1 Day)

Reasons for not completing this period:

Period 2 (7 Days)

Analysis population for the primary outcome, as defined in the registry: All participants who had at least one study treatment and had evaluable pharmacokinetic (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.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics: Area Under the Concentration Versus Time Curve of Cephalexin From Time Zero to Infinity [AUC(0-∞)] of Cephalexin Following a Single Dose, measured over Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period.

The primary endpoint is the area under the cephalexin concentration-versus-time curve from time zero to infinity, written as AUC(0-∞). It summarizes drug concentration over time after a dose, extending the measured concentration-time profile from the first measurement through the estimated period beyond the last measurement. The unit is hour*microgram per milliliter.

AUC is used in pharmacokinetic comparisons because it represents overall exposure, rather than concentration at one particular sampling time. The primary outcome timeframe lists predose and postdose measurements at 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period. The endpoint record reports geometric means and geometric coefficients of variation for the treatment groups.

In general, a geometric mean is a measure of central tendency suited to positive values that may have a multiplicative pattern. It is not the same summary as an arithmetic mean. AUC is relevant to a bioequivalence question because the comparison concerns the extent of systemic exposure. However, the registry record does not report an estimated treatment contrast, confidence interval, or acceptance margins for this endpoint. The posted group summaries therefore describe exposure values but do not by themselves answer whether the preparations met a bioequivalence criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, open-label crossover design and reports geometric means with geometric coefficients of variation for the primary outcome. It does not report the statistical analysis plan or an analysis result for a treatment comparison. The concepts below are general explanations of how such methods are commonly interpreted; they do not identify unreported procedures as methods used in this study.

What does a geometric mean summarize?

A geometric mean is a measure of central tendency for positive measurements. Unlike an arithmetic mean, it reflects multiplicative rather than additive variation. This can be useful for pharmacokinetic measurements, which are positive and may be distributed asymmetrically. The registry reports geometric means for AUC(0-∞), but does not say how the values were calculated or whether any particular transformation or model was used.

The posted geometric mean for the reference is 19.1 hour*microgram per milliliter, and for the test it is 19.21 hour*microgram per milliliter. These summarize each treatment's results; they are not a direct estimate of the treatment effect. In a crossover study, a direct comparison would usually use the paired treatment responses, rather than treating each treatment summary as though it came from unrelated participants. The registry record does not report the paired comparison.

What does the geometric coefficient of variation mean?

A coefficient of variation expresses variability relative to a central value. A geometric coefficient of variation is used with geometric summaries and describes relative spread on a multiplicative scale. The registry reports 16.75 for the reference and 17.55 for the test. These figures are not confidence intervals, and they do not show the range of individual participant values. Without individual data or additional distributional summaries, they cannot show whether the participant-level responses overlap or how uncertain a treatment contrast would be.

In general, over-dispersion means that observed variability is greater than a statistical model expects. Accounting for variability appropriately matters because underestimating it can make uncertainty appear too small. The registry's reported coefficients of variation provide information about relative spread, but the analysis model and any assessment of over-dispersion are not reported in the registry record.

Why does the crossover structure matter?

In general, a crossover study compares treatments received by the same participant in different periods. Because each participant can serve as their own comparison, stable differences between participants may be less influential than in a parallel-group design. The design also means that the analysis needs to consider the paired nature of observations and may need to examine period or sequence effects. The registry reports two periods, two treatments, two sequences, and randomized allocation, but does not report sequence assignments, a washout interval, or the statistical treatment of period and sequence.

The study summary says at least 7 hours passed between study periods. That interval is a recorded design detail; it does not establish how the analysis addressed any carryover or period effects. The registry record does not describe a carryover assessment or provide enough information to evaluate the adequacy of the interval for that purpose.

What would a confidence interval add?

In general, a confidence interval describes statistical uncertainty around an estimated quantity, such as a treatment contrast. It helps distinguish the point estimate from the range of values compatible with the data and analysis assumptions. A confidence interval for a bioequivalence comparison can be assessed against prespecified acceptance limits. No confidence interval or acceptance limits are reported for the primary endpoint in the registry record, so the precision of the comparative effect and its relation to any criterion cannot be assessed from the posted summaries.

A p-value, when reported, addresses compatibility of data with a specified null hypothesis under an analysis model. It does not directly establish equivalence, and a non-significant result is not proof that two treatments are equivalent. No p-value or formal comparison result is reported for the primary outcome. The registry lists zero posted analyses.

How should planning illustrations be understood?

In general, a sample-size calculation estimates how many participants would be needed under stated assumptions to detect a chosen effect with a specified statistical procedure. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence about what the trial was designed to detect or what it could establish after enrollment.

Any sample-size illustration based on an observed effect is a planning calculation, not observed power. Observed power is not a substitute for interpreting an estimated effect and its uncertainty. No planning-output values are reported in the registry record, and the record does not provide the trial's own sample-size justification. The illustration assumptions therefore cannot be used to infer the trial's intended statistical power or to judge whether the enrollment was adequate for a formal bioequivalence conclusion.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary pharmacokinetic outcome, AUC(0-∞), and two secondary outcomes: Cmax and Tmax. The results for those secondary outcomes are not reported in the registry record. The record lists zero posted analyses, so it does not provide a set of inferential results across which multiplicity can be assessed.

Multiplicity arises when several outcomes, comparisons, or analyses are tested. In general, conducting multiple tests can increase the chance of at least one apparently noteworthy result; analysis plans may address this by defining a primary outcome, setting a testing sequence, or adjusting inference. The registry record does not report a multiplicity strategy, a statistical analysis plan, or whether secondary outcomes were intended to support confirmatory conclusions.

The primary outcome population is described as participants who had at least one study treatment and evaluable pharmacokinetic data. The outcome counts are 25 for the reference and 25 for the test, while enrollment is listed as 28. The reason for the difference is not reported in the registry record. The record does not describe missing-data handling, exclusions, protocol deviations, or whether all randomized participants were analyzed according to assigned sequence.

In general, missing pharmacokinetic data can affect a treatment comparison if the availability of measurements is related to treatment response or study participation. Without reasons for missingness and a stated analysis approach, the effect of missing data cannot be evaluated. The record also does not report whether any sensitivity analyses were planned or performed. These gaps limit assessment of how representative the reported primary outcome population is of all enrolled participants and how robust the result is to analytic choices.

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.

For the reference treatment, the registry reports 0 serious adverse events among 28 at risk and 0 other adverse events among 28 at risk. For the test treatment, it likewise reports 0 serious adverse events among 28 at risk and 0 other adverse events among 28 at risk. These are the posted counts for the two treatment groups. Death counts are not reported in the registry record.

The adverse-event figures should be read as counts in this study record, not as proof that either preparation has no risks. A zero count means that no events were recorded in the relevant reported category for the listed group; it does not establish that an event cannot occur or describe risks beyond the trial's observation. The registry does not provide serious adverse event terms, and the record does not give additional details about event definitions, collection procedures, or follow-up for safety.

Because this was a crossover study, participants received both preparations in different periods. The adverse-event counts are presented by treatment group, but the registry does not explain how events in participants exposed to both treatments were attributed or analyzed. The figures therefore describe the recorded safety counts without establishing a comparative safety difference.

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

The record describes a randomized phase 1 crossover study in fasting healthy volunteers, comparing two single-dose cephalexin capsule preparations. The primary endpoint is AUC(0-∞), a measure of drug exposure over time. The posted geometric means are 19.1 hour*microgram per milliliter for the reference and 19.21 hour*microgram per milliliter for the test. The associated geometric coefficients of variation are 16.75 and 17.55.

These results show the treatment-specific summary values recorded for the primary pharmacokinetic outcome. They do not provide a treatment contrast, its confidence interval, or a formal test of bioequivalence. The registry does not report bioequivalence margins or a conclusion about whether the preparations met them. It would therefore go beyond the posted data to state that the products were bioequivalent or not bioequivalent.

The study's crossover design is relevant because, in general, responses under both treatments can be compared within the same participant. But the registry does not report the paired analysis, the handling of period or sequence, or participant-level results. The two group geometric means and their coefficients of variation do not reconstruct that analysis or show its uncertainty.

The record also lists Cmax and Tmax as secondary outcomes, but their results are not reported in the registry record. It reports zero serious and zero other adverse events for each treatment group, with 28 at risk for each category and treatment. The death counts are not reported. These recorded counts are limited to the listed safety categories and do not establish that risk is absent.

Overall, the posted information allows a descriptive reading of the primary outcome summaries and safety counts. It does not establish the comparative precision, statistical significance, or bioequivalence status of the preparations. The registry record does not report the detailed statistical plan, sample-size justification, or missing-data procedures needed to assess those questions more fully.

13. Why This Trial Matters Statistically

This study is statistically interesting because it uses a crossover structure for a comparison of two formulations in the same broad clinical setting. In general, crossover designs can make within-participant treatment contrasts informative by reducing the influence of stable differences between participants. That benefit depends on an analysis that respects the paired observations and considers period and sequence. The registry identifies the design but does not report the analysis details needed to see how those features were handled.

The primary endpoint, AUC(0-∞), represents overall pharmacokinetic exposure after a single dose. The registry reports geometric means and geometric coefficients of variation, which are useful descriptive summaries for positive measurements. Yet a bioequivalence question is not answered simply by placing two group summaries side by side. It depends on a treatment comparison, its uncertainty, and prespecified acceptance limits. Those elements are not reported in the registry record.

The trial also illustrates the distinction between descriptive evidence and inferential evidence. The primary outcome values provide a view of the recorded central tendency and relative variability. Without a reported comparative estimate and confidence interval, readers cannot assess the precision of the difference or ratio on the analysis scale. The record's zero posted analyses is important context: the displayed summaries do not substitute for an inferential result.

Finally, the difference between the listed enrollment and the primary outcome counts raises a question about analysis populations and missing outcome data. The record identifies who was included in the primary outcome population, but does not explain the counts or describe missing-data procedures. This makes transparent reporting of participant flow, exclusions, and analysis methods particularly relevant to interpreting a crossover pharmacokinetic study.

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 important limitation for interpreting the primary result is the absence of a reported treatment comparison. The registry provides treatment-specific geometric means and geometric coefficients of variation, but not a contrast estimate, confidence interval, p-value, or formal bioequivalence conclusion. The acceptance margins for such a conclusion are not reported in the registry record.

The statistical analysis plan is not reported. In particular, the record does not explain how the paired crossover data were analyzed or whether period, sequence, or carryover considerations were addressed. The study summary records at least 7 hours between periods, but does not describe how this interval was selected or whether carryover was assessed. The sequence assignment details are also not reported.

The primary outcome population consisted of participants with at least one study treatment and evaluable pharmacokinetic data. Its treatment-specific counts are 25 for each preparation, while enrollment is listed as 28. The reasons for the difference, participant flow, exclusions, and handling of missing data are not reported in the registry record. The record also does not give participant-level measurements, which would be needed to examine the distribution of paired responses.

Results for the two listed secondary pharmacokinetic outcomes are not reported. The multiplicity plan, if any, is not reported in the registry record. The safety information is limited to the posted serious and other adverse event counts; death counts are not reported, and event terms and collection details are absent. Finally, the record does not report a sample-size justification. These limitations restrict both statistical and clinical interpretation of the posted summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Cephalexin Capsules in Healthy Participants — NCT02123446.
• Registry record last updated 2015-07-15; status last verified 2015-06.
• Results first posted 2015-05-27.
• 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

NCT02123446 is a completed phase 1 randomized, open-label, two-period crossover study sponsored by Eli Lilly and Company. It enrolled fasting healthy volunteers and compared single oral doses of a Mexico-manufactured cephalexin reference capsule with an Italy-manufactured test capsule. The study began in 2014-04 and had primary completion in 2014-05.

The primary outcome was AUC(0-∞), reported as a geometric mean of 19.1 hour*microgram per milliliter for the reference and 19.21 hour*microgram per milliliter for the test. The corresponding geometric coefficients of variation were 16.75 and 17.55. A formal treatment comparison, confidence interval, and bioequivalence conclusion are not reported in the registry record. Cmax and Tmax are listed as secondary outcomes, without posted results.

The registry reports zero serious and zero other adverse events for each treatment group. Death counts are not reported. The primary outcome population and treatment-specific counts are described, but the reason these counts differ from the enrollment entry is not reported.