A Study of Cephalexin Liquid for Pediatrics in Healthy Adults Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Cephalexin Liquid for Pediatrics in Healthy Adults Participants (NCT02123472), 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

This was a pharmacokinetic comparison, not a trial of treatment for an infection. Its stated purpose was to compare two preparations and assess whether they were essentially the same. The primary outcome was area under the concentration-versus-time curve from time zero to infinity, abbreviated AUC(0-∞). The listed unit is hour*microgram per milliliter (h*µg/mL).

The study used a randomized, open-label, two-period, two-treatment, two-sequence crossover design. In a crossover, each participant receives both treatments in different periods, so the comparison can use measurements from the same participant under each treatment. The registry says participants received one preparation in each period, with at least 7 hours between periods. Sequence assignments and the number of participants assigned to each sequence are not reported in the registry record.

The question is therefore whether the recorded exposure estimates support a precise comparison between these preparations under the study conditions. The registry record includes arm-level geometric means and geometric coefficients of variation. It does not include a treatment-effect estimate, confidence interval, or prespecified acceptance limits. Those omissions mean the posted outcome summaries alone cannot establish whether a formal bioequivalence criterion was met.

3. Trial Design

This was a phase 1 randomized, open-label crossover study of cephalexin in fasting healthy volunteers. Its official title describes a two-period, two-treatment, two-sequence design and single doses of two oral suspensions containing 125 mg/5 ml of cephalexin. One preparation was manufactured in Italy and identified as the test; the other was manufactured in Mexico and identified as the reference. The sponsor was Eli Lilly and Company.

The registry record lists enrollment of 28 and a completed status. The start and primary completion dates are both recorded as 2014-05. The brief summary says the study had two periods, with participants receiving one preparation in each period and at least 7 hours between periods. It estimates that participation would take about 2 days, excluding screening or follow-up. The actual dates of individual study visits and the duration of follow-up are not reported in the registry record.

Randomization was reported, but the method used to generate or conceal the sequence is not reported in the registry record. The study was open-label, with no masking. The numbers assigned to each sequence, any period-specific completion counts, and whether any participants changed or discontinued their assigned sequence are not reported in the registry record.

The primary outcome population is described as participants who had at least one study treatment and evaluable pharmacokinetic data. The outcome lists 26 participants for the test preparation and 26 for the reference preparation. These are treatment-specific outcome counts; the record does not state how many participants had evaluable paired measurements or explain the difference between enrollment and the outcome counts.

Measurements were scheduled before dosing and at multiple post-dose times through 7.0 hours in each period. The listed secondary outcomes were time to maximum observed concentration (Tmax) and maximum concentration (Cmax). The registry record reports no analyses for these outcomes. It also does not report details of the dose administration procedure, sample handling, assay validation, or the protocol’s statistical analysis plan.

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)

Period 2 (7 Days)

Reasons for not completing this period:

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, or AUC(0-∞), after a single dose. Concentration measurements were scheduled before dosing and at specified times from 0.25 through 7.0 hours in each period. AUC represents drug exposure over time: it summarizes the concentration profile rather than describing concentration at one sampling time. Extending the area to infinity uses the observed profile and an extrapolated terminal portion; the registry record does not describe the calculation method or how much of the estimate came from extrapolation.

Pharmacokinetic exposure measures are used in comparisons of formulations because they describe how much drug enters systemic circulation over time. In bioequivalence evaluations, exposure summaries are generally compared using a treatment contrast and its uncertainty, assessed against prespecified limits. That is a general explanation of the approach; the limits and analysis plan for this study are not reported in the registry record.

The posted primary outcome is expressed as a geometric mean with geometric coefficient of variation. A geometric mean is a summary suited to positive measurements that may have a right-skewed distribution. The geometric coefficient of variation describes variability on a multiplicative scale. These summaries describe the treatment-specific exposure data, but do not by themselves provide the treatment contrast or its precision.

The record also lists Cmax and Tmax as secondary outcomes. Cmax is the maximum observed concentration, while Tmax is the time at which that maximum is observed. They characterize different parts of the concentration profile and do not replace the primary exposure measure. Their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, open-label, and crossover. These design features explain how the treatment comparison was organized, but they do not by themselves specify the statistical analysis. The registry record does not report the statistical model, the treatment contrast definition, the handling of period or sequence, or the decision criteria for bioequivalence.

What does a crossover design contribute?

In a crossover study, participants receive more than one treatment in separate periods. Because a participant can contribute measurements under both treatments, comparisons can account for stable differences between people. This within-participant feature can make a treatment comparison more informative than treating the treatment groups as unrelated, provided the analysis uses the pairing appropriately. The study summary says each participant was to receive one preparation in each of two periods, with at least 7 hours between periods. Whether that interval was adequate for the protocol’s pharmacokinetic aims, and what rationale was used to select it, are not reported in the registry record.

Period and sequence are potential design considerations in crossover trials. A period effect is a difference associated with when a treatment was received; sequence refers to the order in which treatments were assigned. Depending on the setting and analysis plan, carryover from one period may also matter. These are general methodological considerations, not findings about this study. The registry record does not report results for period, sequence, or carryover, or say how such effects were handled.

What do the reported summaries mean?

The primary outcome is reported as a geometric mean. Geometric summaries are often used for positive pharmacokinetic measurements because such data can be skewed, and because proportional changes can be more relevant than equal absolute changes. A geometric coefficient of variation summarizes spread on a multiplicative scale. It is not a confidence interval and does not, on its own, indicate how precisely the treatment contrast was estimated.

In a common general approach to bioequivalence analysis, exposure values are transformed to the logarithmic scale, analyzed with a model suited to the trial design, and the treatment contrast is then expressed on the original scale. A confidence interval for that contrast is compared with prespecified acceptance limits. This describes a general method only. The registry record does not state whether this study used that method, what limits were prespecified, or what confidence level or model was used. No treatment contrast or confidence interval is posted.

Why does variability matter?

Variability affects how precisely a treatment comparison can be estimated. In a crossover study, within-participant variability is especially relevant because the comparison depends on paired observations. The posted geometric coefficients of variation describe arm-level variability but do not separate within-participant from between-participant variation. A valid assessment of the comparison’s precision therefore requires analysis details and paired data or a reported contrast with uncertainty, none of which are reported in the registry record.

Over-dispersion is a general issue when observed variability is greater than a statistical model assumes. If a model fails to account for that extra variability, standard errors and confidence intervals may be too narrow. The registry record does not report evidence of over-dispersion, the model’s variance assumptions, or any diagnostic checks. This concept should not be taken as evidence that over-dispersion occurred in this study.

What can a confidence interval tell a reader?

A confidence interval communicates the uncertainty around an estimated treatment contrast under a specified analysis. A narrow interval indicates greater precision than a wide interval, while the interval’s location relative to prespecified limits is important for a bioequivalence conclusion. An interval is not the probability that the true value lies within its particular bounds. No confidence interval for the primary contrast is reported in the registry record, so neither its precision nor its relation to acceptance limits can be assessed.

The outcome lists the number of participants and arm-level summaries, but not an inferential analysis. The record indicates zero posted analyses. This does not mean that no analyses were performed; it means inferential analysis results are not reported in the registry record. No independent recalculation is appropriate from the arm-level summaries alone because the pairing and analysis details are not reported.

How should planning calculations be understood?

Sample-size calculations are planning exercises that ask how many participants per arm might be needed under specified assumptions to detect an effect with a chosen power and significance level. The planning description for this study states a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect set as a stated fraction of the observed effect. Such calculations are illustrations based on assumptions, not observed power and not evidence that the study was adequately powered. They should not be confused with the actual analysis or the trial’s original design rationale. The rationale and sample-size justification used for the trial are not reported in the registry record.

For a crossover design, planning depends on assumptions about within-participant variation and the treatment contrast. The planning description does not establish which assumptions were used in the original protocol, and no original power calculation or target sample size is reported in the registry record. Any planning illustration should therefore be read as conditional rather than as a reconstruction of the study’s design process.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome, AUC(0-∞), and two secondary pharmacokinetic outcomes: Tmax and Cmax. It does not report a multiplicity adjustment, a hierarchy among outcomes, or a plan for controlling the chance of false-positive findings across multiple tests. The record lists zero analyses, so it provides no reported tests across which multiplicity could be assessed. Whether the protocol specified an approach is not reported in the registry record.

The primary outcome population included participants who had at least one study treatment and evaluable pharmacokinetic data. The outcome lists 26 participants for the test preparation and 26 for the reference preparation, while enrollment was 28. The registry record does not explain the difference, identify which participants were excluded, or report whether the same participants contributed data under both treatments. It also does not give missing-data counts by period or sampling time, reasons for missingness, or a method for handling missing measurements.

In a crossover study, missing data in one period can affect whether a participant contributes a complete paired comparison. General approaches depend on the analysis plan and the pattern and cause of missingness; no particular method can be attributed to this study from the registry record. The record does not report imputation, sensitivity analyses, or an analysis population based on complete pairs.

The record’s description of evaluable pharmacokinetic data clarifies the population considered for the primary outcome, but it does not specify how evaluability was defined. The protocol definition, any exclusions for protocol deviations, and any distinction between safety and pharmacokinetic populations are not reported in the registry record. These gaps limit assessment of the consequences of missingness and the robustness of the outcome summaries.

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.

The registry reports no serious adverse events for the test preparation among 28 participants at risk, and no serious adverse events for the reference preparation among 28 participants at risk. It also reports no other adverse events for either preparation among 28 participants at risk. These are the recorded event counts for the two treatment groups.

The outcome does not establish that no events of any kind occurred outside the recorded categories or observation period. The registry record does not describe the safety observation window, the event collection method, or how adverse events were attributed to a treatment. It also does not report death counts; those figures are not reported in the registry record. No serious adverse-event terms are listed.

Because the study used a crossover, participants could receive both preparations in different periods. The treatment-specific at-risk counts should be read as the recorded counts for each preparation, not added together to infer a number of unique participants. The record does not provide person-time or a detailed account of exposure periods.

These safety entries are descriptive reporting. They do not establish comparative safety, particularly without inferential analysis, a detailed event definition, or information about follow-up. They also do not support medical advice or conclusions about use in children: the study population was fasting healthy volunteers, and the title’s reference to pediatrics describes the preparation rather than the participant population.

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

The posted results establish that the registry record contains treatment-specific geometric mean AUC(0-∞) estimates for the two cephalexin preparations, along with geometric coefficients of variation and outcome counts. They describe the pharmacokinetic exposure summaries observed among participants with evaluable data. The study was randomized and crossover, with each participant scheduled to receive both preparations in separate periods.

The record does not establish whether the preparations met a formal bioequivalence standard. That conclusion ordinarily depends on a prespecified treatment contrast, its confidence interval, and acceptance limits. None of those elements is reported in the registry record. The arm-level geometric means cannot be substituted for the required inferential comparison, and a visual comparison of the values does not resolve uncertainty.

The findings also do not show whether the preparations have the same clinical effects or safety profile. The study assessed pharmacokinetic outcomes in healthy volunteers following single doses; it did not report a clinical efficacy outcome in patients being treated for infection. Its results therefore do not answer how either preparation performs in clinical care or in a pediatric population.

The primary outcome population was defined by receipt of at least one treatment and evaluable pharmacokinetic data. Although the record reports outcome counts for each treatment, it does not explain the difference from the enrollment count, report the number with complete paired data, or describe missing measurements. This leaves uncertainty about the composition of the analyzed population and limits independent assessment of the analysis.

The study can be understood as a structured formulation-comparison experiment with a pharmacokinetic exposure endpoint. Its descriptive results are useful for identifying what outcome was measured and the summaries posted for each preparation. But the absence of a reported contrast, uncertainty interval, analysis method, and decision threshold means that the strength and precision of the comparison cannot be determined from the registry record. The appropriate conclusion is limited to those reported descriptive summaries, without asserting equivalence, difference, or clinical effect.

13. Why This Trial Matters Statistically

This study illustrates why the design and analysis details matter when interpreting a pharmacokinetic comparison. A crossover design allows a participant to receive both formulations, potentially making within-participant comparisons informative. But the advantage depends on an analysis that respects the pairing and accounts for relevant design features. Treatment-specific summaries alone do not show how that comparison was estimated.

It also illustrates the distinction between descriptive results and a formal bioequivalence conclusion. Geometric means summarize exposure under each preparation, while the decision about bioequivalence depends on a treatment contrast, its uncertainty, and prespecified limits. Without those elements, the reported exposure values do not answer the formal comparison question, regardless of how similar or different they may appear to a reader.

The registry record distinguishes enrollment from the population contributing to the primary outcome. That distinction is important: a reader needs to know which participants contributed data, whether measurements were paired, and why some participants or observations may be absent. Here, the population definition and arm-specific counts are reported, but the reasons for the enrollment-to-outcome difference and the missing-data pattern are not.

Finally, the study’s population and endpoint define the scope of any interpretation. These were fasting healthy volunteers receiving single doses, and the primary outcome was pharmacokinetic exposure. The study does not report clinical outcomes in patients. Reading the record narrowly helps separate what was measured from broader claims about treatment or patient benefit.

For statistical education, the case is a reminder that design labels and summary statistics do not replace a complete analysis report. The record identifies a randomized crossover experiment and posts geometric summaries, but omits the model, contrast, confidence interval, multiplicity approach, and bioequivalence limits needed to evaluate the primary inferential 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 main limitation for statistical interpretation is that the registry record does not report an inferential comparison for the primary outcome. There is no treatment contrast, confidence interval, p-value, analysis model, or bioequivalence acceptance range. Consequently, the precision and formal interpretation of the observed exposure summaries cannot be evaluated.

The record describes a crossover design but does not report sequence assignments, period-specific results, paired-data counts, or how the analysis addressed period or sequence. The relationship between the 28 enrolled participants and the 26 participants listed for each treatment outcome is not explained. The extent and causes of missing data, and any exclusions from the pharmacokinetic population, are not reported in the registry record.

The study was open-label. The record does not explain whether this could have affected any study procedures or assessments, nor does it give details of randomization generation or concealment. These design and implementation details are not reported in the registry record.

The posted primary endpoint is a pharmacokinetic measure following single doses in fasting healthy volunteers. Clinical outcomes in patients, repeated dosing, and pediatric participants are not described as study populations or endpoints. The findings therefore have a limited scope and should not be extended to those contexts.

The registry record lists secondary outcomes but reports no analyses for them. It does not describe a multiplicity plan, detailed sample-size justification, interim analyses, missing-data procedures, or the statistical analysis plan. These omissions do not show that such procedures were absent from the study; they mean they are not reported in the registry record. The adverse-event entries are also limited: observation duration and event-collection details are not reported, and death counts are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Cephalexin Liquid for Pediatrics in Healthy Adults Participants — NCT02123472.
• Registry record last updated 2015-06-25; status last verified 2015-06.
• Results first posted 2015-06-25.
• 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 crossover study sponsored by Eli Lilly and Company. It enrolled 28 fasting healthy volunteers and compared single oral doses of cephalexin suspension manufactured in Italy and Mexico. Participants were scheduled to receive each preparation in a separate period, with at least 7 hours between periods.

The primary outcome was AUC(0-∞) through 7.0 hours of scheduled sampling in each period. The record reports geometric means of 36.26 h*µg/mL for the test preparation and 38.2 h*µg/mL for the reference, with geometric coefficients of variation of 15.51 and 14.38. Each treatment outcome lists 26 participants. The record lists Tmax and Cmax as secondary outcomes but reports no analyses for them.

No formal primary comparison, confidence interval, or bioequivalence conclusion is reported in the registry record. Serious and other adverse-event counts are reported as zero for both treatment groups; death counts are not reported in the registry record.