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

1. Trial at a Glance

This page covers the registry results for A Study of Cephalexin Suspension in Healthy Participants (NCT02123459), a randomized phase 1 study. The primary outcome is Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Cephalexin Following a Single Dose.

2. Clinical Question

The study asked whether two oral cephalexin suspension preparations had comparable pharmacokinetic exposure after a single dose in fasting healthy volunteers. It compared a reference preparation manufactured in Mexico by Eli Lilly y Compañía de México, S.A. de C.V. with a test preparation manufactured in Brasil by Antibioticos do Brasil Ltda for Eli Lilly y Compañía de México, S.A. de C.V. Both preparations are identified in the official title as 250 mg/5 ml suspensions.

The question is pharmacokinetic rather than a comparison of clinical symptoms or treatment outcomes. The registry record also lists maximum concentration and time to maximum observed concentration as secondary outcomes. These measures describe different aspects of the concentration-time profile, while the primary endpoint focuses on total estimated exposure.

3. Trial Design

This was a randomized, open-label, two-period, two-treatment, two-sequence crossover study in healthy volunteers. Each participant was intended to receive both cephalexin preparations, with one preparation given in each study period. The registry summary states that at least 7 hours would pass between the study periods. The study was registered as Phase 1 and is marked completed.

A crossover design uses participants as their own comparison: measurements after one preparation can be compared with measurements after the other preparation in the same participant. This can account for stable differences between participants, but a valid treatment comparison still depends on the period and sequence structure and on an analysis that reflects the paired observations. The registry record identifies two sequences but does not report how many participants were assigned to each sequence or provide sequence-specific results.

The study was open label, so masking was not used. The record describes a single oral dose in each period and identifies the participants as fasting healthy volunteers. It says the study was expected to last about 2 days per participant, excluding screening or follow-up; this is the registered expectation, not a reported measurement of actual participation time. The study start and primary completion are both recorded as 2014-05.

Enrollment was 28. The posted primary outcome results include 27 participants for each treatment, and the outcome population is defined as those with at least one study treatment and evaluable pharmacokinetic data. The registry record does not explain the difference between the enrollment count and the reported endpoint counts, nor does it give participant flow by period or sequence.

The intervention is listed as cephalexin. The arm descriptions distinguish a reference product manufactured in Mexico from a test product manufactured in Brasil. No additional treatment groups are described. The record does not report a washout rationale, protocol-specific handling of period effects, or a sample-size justification. Those details cannot be inferred from the crossover structure alone.

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 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 was the area under the cephalexin concentration-versus-time curve from time zero to infinity, abbreviated AUC(0-∞). It is a pharmacokinetic measure of total exposure over time after a dose. The registry specifies the unit as hours*microgram per milliliter (h*μg/mL) and reports the endpoint as a geometric mean with geometric coefficient of variation.

Concentrations were scheduled for measurement before dosing and at the listed post-dose times in each period: 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. The endpoint combines information across the concentration-time profile, including an estimate extending beyond the final listed sampling time. How that extrapolation was performed is not reported in the registry record.

In general, total exposure is useful in a formulation comparison because it summarizes how much drug reaches the circulation over time. Maximum concentration and time to maximum concentration, listed as secondary outcomes, describe the peak level and when it occurs. Together, these pharmacokinetic measures characterize the observed concentration profile, but the registry record does not provide inferential results for the secondary outcomes.

The posted geometric means were 29.54 for the reference preparation and 35.86 for the test preparation. Their reported geometric coefficients of variation were 22.92 and 14.45, respectively. These are descriptive arm-level summaries. Without a reported treatment contrast and its uncertainty, they do not by themselves establish the size or precision of the within-participant difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design is a randomized crossover comparison. In general, crossover trials assign participants to treatment sequences so that each participant receives each treatment in separate periods. This makes the participant a natural comparison unit and can reduce the influence of stable differences between people. The treatment effect is not obtained simply by comparing unrelated group averages: the analysis needs to use the within-participant structure and address any relevant period or sequence effects. The registry record identifies the design as two-period, two-treatment, and two-sequence, but does not describe the statistical model or its handling of those effects.

What the geometric summaries mean

The primary endpoint is reported as a geometric mean. In general, geometric means are suited to positive measurements whose variation is better understood proportionally than as fixed additive differences. They are calculated on a logarithmic scale and transformed back to the original scale for reporting. The posted geometric means are 29.54 for the reference preparation and 35.86 for the test preparation.

The geometric coefficient of variation describes relative dispersion on the scale used for these pharmacokinetic data. The reported values are 22.92 for the reference preparation and 14.45 for the test preparation. Dispersion is not the same as uncertainty in the mean or uncertainty in a treatment contrast. A confidence interval, if reported, would instead describe a range of estimates compatible with the data and the analysis assumptions. No confidence interval is posted for this endpoint.

Why a paired analysis matters

Because participants received both preparations in separate periods, their measurements are related. A valid comparison should preserve that relationship rather than treat the two treatment summaries as if they came from independent groups. General crossover analyses commonly compare log-transformed pharmacokinetic measurements and estimate a treatment contrast within a model that accounts for the design. That is a general description, not a claim about the method used in this study. The registry record does not report the transformation, model, covariates, treatment contrast, or standard error used by the sponsor.

Period effects can occur when measurements differ systematically between study periods, while sequence effects can reflect the assigned order. Carryover is another design consideration when an earlier treatment might influence a later-period measurement. The registered interval between periods was at least 7 hours, but the registry record does not explain the rationale for that interval or report assessments of period, sequence, or carryover effects. It would be inappropriate to infer how these issues were addressed.

Sampling and endpoint construction

The primary endpoint was AUC(0-∞), based on concentrations scheduled before dosing and at the stated post-dose times through 7.0 hours in each period. In general, area under a concentration-time curve can be estimated from measured concentrations, with an extrapolated component used to extend the estimate toward infinity. The registry record does not state the calculation method, the contribution of extrapolation, or criteria for judging a pharmacokinetic profile evaluable. It reports the unit as hours*microgram per milliliter (h*μg/mL).

The primary outcome population is defined as participants who had at least one study treatment and evaluable pharmacokinetic data. The posted results give 27 observations for each preparation. The record does not state whether all participants with a result for one treatment also had a paired result for the other, how many participants completed each period, or how incomplete profiles were treated. Those details are important because a crossover contrast ordinarily depends on paired information.

Inference and planning

Statistical inference would usually present an estimated treatment contrast together with a measure of uncertainty, such as a confidence interval, and may include a test against a prespecified null hypothesis. For a bioequivalence assessment, the decision also depends on prespecified acceptance criteria. Neither the formal contrast nor its uncertainty, test, or acceptance limits are reported in the registry record. The arm-level geometric means and dispersion values therefore remain descriptive rather than a substitute for the sponsor's inferential analysis.

The registry record indicates that a planning illustration uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. Such planning illustrations are not the trial's observed power and do not demonstrate that the trial had adequate power for its intended analysis. The registry record does not report the trial's own sample-size justification, target effect, or design assumptions. No numerical planning estimates are stated in the record information.

The record lists no analyses. That absence means the registry entry does not describe the sponsor's model, inferential outputs, or decision process. It does not establish that no analysis was performed outside the registry. Without the analysis details, readers cannot verify whether the posted summaries correspond to the planned estimand or determine the precision of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary exposure endpoint and two secondary pharmacokinetic outcomes: maximum concentration and time to maximum observed concentration. It does not report a plan for controlling multiplicity across these outcomes, a hierarchy for interpreting them, or a rule for designating any analyses as confirmatory. When multiple outcomes are examined, the chance of at least one apparently unusual result can change; in general, a prespecified approach helps readers understand how evidence across outcomes is interpreted. The registry record does not describe such an approach.

The primary endpoint population is defined as participants who had at least one study treatment and evaluable pharmacokinetic data. Enrollment was 28, while the posted primary endpoint results report 27 for each treatment. The reason for this difference is not reported in the registry record. It also does not explain whether the same participants contributed to both treatment summaries or how results from incomplete periods were handled.

Missing-data methods, rules for excluding profiles, and sensitivity analyses are not reported in the registry record. In a crossover study, missing measurements can affect the availability of within-participant comparisons; separate treatment counts do not show whether complete pairs were available. The record also does not report an intention-to-treat or per-protocol analysis population, or any departures from the stated evaluable pharmacokinetic population.

Although the registry defines the primary population, it does not give enough information to assess the consequences of missing or nonevaluable data. The absence of posted analyses also leaves the treatment of secondary outcomes and any multiplicity adjustment unreported.

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 record lists 28 participants at risk for serious adverse events in each treatment group. It reports 0 participants with a serious adverse event in the reference group and 0 in the test group. These are the posted serious-event counts for the groups, not an estimate of comparative safety or a test of whether the preparations differ.

For other adverse events, the record lists 28 participants at risk in each group, with 0 affected in the reference group and 2 affected in the test group. The record does not provide event terms for these other events in the information, so their nature, severity, timing, and relationship to study treatment cannot be described. The serious-event terms list is empty.

Deaths are not reported in the registry record. A blank death count should not be interpreted as a reported count of zero. The record also does not provide additional detail about how adverse events were collected, classified, or assessed for relationship to treatment. These safety figures are limited to the registry's posted counts and do not provide a complete account of clinical safety.

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

The results establish that the registry record contains descriptive pharmacokinetic summaries for the reference and test cephalexin suspensions. For AUC(0-∞), the reported geometric means are 29.54 and 35.86, with geometric coefficients of variation of 22.92 and 14.45, respectively. The endpoint counts are 27 for each preparation. These values describe the recorded data; they do not quantify the uncertainty of a paired treatment comparison.

The study's stated purpose was to evaluate bioequivalence, but the registry record does not post a treatment contrast, confidence interval, p-value, analysis method, or bioequivalence acceptance limits. Therefore the descriptive results alone do not show whether the formal bioequivalence criteria were met. They also do not establish that the preparations are equivalent or different.

The crossover design means each participant was intended to receive both preparations, but the reported arm summaries do not reveal individual paired responses. Without paired results or an inferential analysis, readers cannot assess how much within-participant variability affected the comparison. The record also does not explain the difference between enrollment and the endpoint counts or describe missing-data handling.

The reported endpoint concerns drug exposure in fasting healthy volunteers after single oral doses. It is not a clinical effectiveness outcome, and these data should not be interpreted as evidence about patient outcomes. The registry record lists maximum concentration and time to maximum observed concentration as secondary outcomes, but does not provide their results in the information.

The safety counts are also limited. No serious adverse events are recorded among the participants listed at risk, and the record reports other adverse events for 0 participants in the reference group and 2 in the test group. Deaths are not reported in the registry record, and details of the other adverse events are not available. Taken together, the entry gives a partial descriptive account, not a complete efficacy, bioequivalence, or safety assessment.

13. Why This Trial Matters Statistically

This study is statistically instructive because the design and the reported summaries answer different parts of a research question. A crossover design is intended to compare treatments within participants, while the posted primary results are separate geometric means and geometric coefficients of variation for each preparation. The design identifies the intended comparison structure; it does not replace the paired analysis needed to quantify that comparison.

Pharmacokinetic endpoints are often summarized using geometric means because their variation can be more naturally expressed proportionally. Here, the record reports geometric means of 29.54 and 35.86 and geometric coefficients of variation of 22.92 and 14.45. These summaries are useful descriptions, but they are not a treatment ratio, a confidence interval, or a bioequivalence decision. Distinguishing descriptive summaries from inferential results is essential when interpreting a registry entry.

The record also illustrates why an endpoint population definition matters. Enrollment was 28, while the posted primary results use 27 per treatment. The population is described as participants with at least one treatment and evaluable pharmacokinetic data, but the registry record does not explain the difference in counts or confirm the availability of complete paired observations. Participant flow and missing-data rules are needed to assess how the reported population relates to the randomized participants.

Finally, the record states the trial's bioequivalence purpose but does not report the inferential method, uncertainty, or acceptance criteria. A stated study objective and descriptive outcome values do not by themselves establish that an objective was achieved. The distinction is broadly useful in clinical research: design, estimation, uncertainty, and decision criteria each contribute separate information, and readers need the relevant pieces to interpret a result.

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 that the registry record does not report the within-participant treatment contrast or its uncertainty. The posted geometric means and geometric coefficients of variation are descriptive summaries, not a formal bioequivalence result. The record does not state the statistical model, confidence interval, test statistic, p-value, or acceptance limits.

The endpoint population is defined as participants with at least one treatment and evaluable pharmacokinetic data, with 27 participants reported for each preparation. Enrollment was 28, but the reason for the difference is not reported in the registry record. Participant flow by period and sequence, the number with complete paired data, and the handling of missing concentrations or incomplete profiles are also not reported.

The registry record does not provide results for the listed secondary outcomes of maximum concentration and time to maximum observed concentration. It does not describe a multiplicity plan, outcome hierarchy, sample-size justification, or protocol-specific analysis plan. The sample-size planning assumptions do not substitute for the trial's own design justification or for observed inferential results.

The study was open label and involved fasting healthy volunteers receiving single oral doses. The registry does not report whether these features affect measurement or interpretation, and the results do not directly describe patient outcomes. The registered sampling schedule and endpoint definition are available, but the method for estimating AUC(0-∞), including extrapolation, is not reported.

Safety reporting is limited to counts. The record does not provide terms or clinical detail for the other adverse events, and deaths are not reported in the registry record. These limitations mean the posted entry does not provide a full statistical or clinical account of the comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Cephalexin Suspension in Healthy Participants — NCT02123459.
• Registry record last updated 2015-05-27; status last verified 2015-05.
• 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

The registry record describes a completed Phase 1 randomized, open-label, two-period, two-treatment, two-sequence crossover study of cephalexin suspensions in fasting healthy volunteers. Enrollment was 28. Participants were intended to receive each preparation once, with at least 7 hours between periods; the registered expected participation duration was about 2 days, excluding screening or follow-up.

The primary endpoint was AUC(0-∞), reported as a geometric mean with geometric coefficient of variation. The reference and test results were 29.54 and 35.86, with coefficients of variation of 22.92 and 14.45; each treatment result lists 27 participants. The registry record does not report an inferential treatment comparison or a bioequivalence conclusion.

Two secondary pharmacokinetic outcomes are listed, but their results are not reported in the registry entry described. Serious adverse events were reported for 0 participants in each group; other adverse events were reported for 0 participants in the reference group and 2 in the test group. Deaths are not reported in the registry record. The analysis plan, missing-data handling, and sample-size justification are not reported.