Bioequivalence Study Between Two Albendazole 400 mg Tablets in Healthy Adult Participants Under Fed Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study Between Two Albendazole 400 mg Tablets in Healthy Adult Participants Under Fed Conditions (NCT06201559), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) of Albendazole.

2. Clinical Question

This is a pharmacokinetic comparison, not a trial of treatment for intestinal disease. The registry lists intestinal diseases as a condition, but describes the study objective as comparing the extent and rate of absorption of two formulations at the same dose in healthy adults. The primary endpoint is maximum plasma concentration of albendazole; secondary outcomes include additional concentration-time measures for albendazole and albendazole sulfoxide.

The design exposes participants to both formulations across repeated periods, in different orders. That makes the question a within-participant comparison as well as a comparison between formulations. The registry lists two randomized sequences, TRTR and RTRT, where T is the test intervention and R is the reference intervention. The posted primary result combines the four treatment-period groups in an equivalence analysis. The registry record does not report the equivalence margins or enough detail to reconstruct the analysis model independently.

3. Trial Design

The registry describes a completed, randomized, open-label, four-period, two-sequence, single oral dose, full replicate crossover study under fed conditions. It lists phase 1 and enrollment of 70. The sponsor is GlaxoSmithKline. The recorded study dates are 2023-08-21 for start and 2023-09-12 for primary completion.

In a crossover design, participants receive more than one study intervention at different times, so each participant can contribute observations under both formulations. This can support a direct pharmacokinetic comparison by reducing the influence of stable differences between participants. That is a general feature of crossover designs, not evidence about the size of any particular design benefit in this study. The registry does not report the washout duration or other details needed to assess period-to-period separation.

The two sequences alternate the test and reference formulations. Sequence TRTR starts with the test formulation, followed by the reference formulation, then the test and reference formulations again. Sequence RTRT starts with the reference formulation and alternates in the opposite order. The official title calls the study balanced, but the registry record does not describe how balance was achieved or give the sequence allocation counts.

Masking is listed as none, so the study is open label. The registry record does not report the randomization generation method, allocation concealment procedures, or whether laboratory personnel were masked. The arms reported for the primary endpoint are period-specific test and reference groups, with separate observations for the first and second administrations of each formulation. Their reported counts differ, so the period-specific observations should not be treated as identical analysis sets or added to infer the number of participants.

The registry reports a total enrollment of 70, but the pharmacokinetic result rows have their own analysis counts. The registry record does not explain all differences between enrollment and those counts, or provide a participant flow account in the registry record used for this interpretation. Nor does it report a sample-size justification. The trial's actual design rationale and the methods used to determine enrollment are therefore not established by 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

Period 2

Period 3

Period 4

Analysis population for the primary outcome, as defined in the registry: PK population included all participants in Safety set who had at least 1 measurable PK assessment. As pre-specified in Statistical Analysis Plan (SAP), data is collected and reported for PK parameters per study intervention i.e. Test Study Intervention-T1 (1st administration), Test Study Intervention-T2 (2nd administration), and Reference Study Intervention-R1 and Reference Study Intervention-R2 similarly. Only those participants with data available at specified time points have been analyzed.

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 Maximum Plasma Concentration (Cmax) of Albendazole, measured over Pre-dose, 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.50, 5, 6, 8, 10, 12, 14, 18 and 24 hours.

The primary endpoint is maximum plasma concentration, or Cmax, of albendazole, measured in nanograms per millilitre. It represents the highest measured plasma concentration after administration during the concentration-time sampling period. A peak concentration is a pharmacokinetic measure of exposure that can reflect how quickly and how much of a drug reaches the circulation, although it does not by itself describe the whole concentration-time profile.

Blood sampling was scheduled before dosing and at the listed post-dose times through 24 hours. The registry says pharmacokinetic parameters were determined using standard non-compartmental methods. For this endpoint, the registry reports geometric means and geometric coefficients of variation for the period-specific test and reference observations. It also reports an equivalence analysis using the ratio of geometric least-squares means.

Geometric summaries are commonly used for pharmacokinetic measures that are positive and may be right-skewed. The ratio is useful because it expresses the relative scale of the two formulations rather than their absolute difference. General interpretation of bioequivalence depends on the estimated ratio and its uncertainty in relation to prespecified acceptance bounds. Those bounds are not reported in the registry record, so the ratio and confidence interval alone do not establish whether the study met its prespecified equivalence criterion.

Cmax is one component of the concentration-time profile, not a direct measure of clinical benefit or harm. The registry lists several secondary pharmacokinetic endpoints, including area-under-the-curve measures, time to Cmax, half-life, and other parameters for albendazole or albendazole sulfoxide. Their presence gives broader context for the pharmacokinetic assessment, but the primary question remains the comparison of albendazole Cmax.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish the posted period summaries from the reported equivalence result. The registry lists geometric means and geometric coefficients of variation for each administration period, then separately reports a ratio of geometric least-squares means with a confidence interval. These summaries answer related but different questions: the first describe each treatment-period group, while the second estimates a relative contrast under an analysis model.

Why use a crossover comparison?

General explanation: in a crossover study, participants receive different interventions in separate periods. A comparison can use the fact that each participant has observations under both interventions, allowing stable participant characteristics to be controlled through within-participant comparisons. The design also requires careful consideration of period effects, sequence effects, and possible carryover between periods. The registry record identifies a four-period, two-sequence full replicate crossover, but does not report the washout duration, the model terms, or diagnostic assessments for these potential effects. No specific conclusion about their influence can therefore be made.

What does a geometric mean convey?

General explanation: a geometric mean is calculated on a logarithmic scale and then expressed back on the original scale. It is often used for positive concentration measures because such measurements can be skewed, with some observations appreciably larger than others. The geometric coefficient of variation describes relative variability on a multiplicative scale. It is not the same as a standard deviation in the original units, and it does not show how the paired treatment differences vary within participants.

The registry reports geometric means and geometric coefficients of variation for the four administration groups. Those summaries are informative about each group's distributional scale and variability, but do not reveal the covariance between repeated measurements from the same participant. As a result, they are insufficient to independently reconstruct the crossover treatment contrast or its standard error.

How should the ratio be read?

General explanation: a ratio compares the scale of one estimated quantity with another. A ratio near 100 on a percentage-style scale represents similar estimated levels, while uncertainty is conveyed by the confidence interval. The registry reports the ratio of geometric least-squares means as 98.1 and its 90% confidence interval as 86.79 to 110.91. The least-squares means are model-based estimates; they need not be identical to the raw geometric means listed for individual periods.

In a formal bioequivalence assessment, an interval is judged against prespecified lower and upper bounds. The registry record does not report those bounds, the direction convention for the ratio, or the detailed model used to obtain the least-squares means. It is therefore possible to describe the estimate and interval, but not to verify the sponsor's formal equivalence decision from the registry figures alone. The absence of a p-value is not unusual for an equivalence presentation, where an interval and acceptance bounds are typically central, but the record does not state the specific planned decision procedure.

What does a confidence interval mean?

General explanation: a confidence interval is a method for representing uncertainty in an estimated quantity. It is not a range that contains a fixed proportion of individual measurements, and it does not guarantee that the true value lies within the particular interval. The reported 90% confidence interval summarizes the uncertainty associated with the ratio estimate under the analysis assumptions. Those assumptions and the model specification are not fully described in the registry record.

The width of an interval reflects both the information in the data and the variability under the analysis. A crossover estimate may be more or less precise than a comparison based only on separate groups, depending in part on the within-participant correlation. Because the correlation and model details are not reported, the period-specific geometric coefficients of variation cannot be used alone to explain the precision of the ratio interval.

Why do multiple endpoints matter?

General explanation: when a study evaluates several endpoints, repeated testing can increase the chance of finding a nominally notable result by chance if each test is interpreted independently. Researchers may prespecify one primary endpoint, use a testing hierarchy, adjust significance thresholds, or treat other analyses as descriptive. The registry names a primary endpoint and lists secondary pharmacokinetic outcomes and treatment-emergent adverse events. A multiplicity strategy or detailed testing hierarchy is not reported in the registry record. The primary result should therefore be distinguished from the wider set of outcomes, for which results and inferential procedures are not available in the registry record described.

How do planning calculations differ from observed power?

General explanation: sample-size planning calculations depend on assumptions about the effect to detect, variability, allocation, and statistical method. A calculation based on an observed effect is an illustration of planning under stated assumptions, not a retrospective measure of the probability that the completed study detected an effect. Such a calculation should not be called observed power. The registry record does not report the trial's own sample-size justification, so any planning illustration should not be treated as evidence of the study's original design rationale.

Finally, the registry describes the pharmacokinetic population as participants in the safety set who had at least one measurable pharmacokinetic assessment. It does not provide detailed rules for handling missing measurements, exclusions, below-quantification values, or incomplete periods. Those details can affect which observations contribute to the model and how uncertainty is estimated. Without them, the analysis can be described at the level reported, but not fully reproduced.

10. Analyses Reported by the Sponsor

The registry's reported analysis is the sponsor's equivalence result: a ratio of geometric least-squares means of 98.1, with a 90% confidence interval from 86.79 to 110.91. The record identifies the analysis as an equivalence analysis and gives no p-value. It does not state the equivalence margins or provide enough model detail to reproduce the sponsor's estimate from the period-specific geometric summaries.

The posted period-specific means and coefficients of variation are descriptive summaries, not a substitute for the sponsor's model-based crossover analysis. They do not include the within-participant covariance needed to reconstruct the treatment contrast and its uncertainty. No recalculated analysis is available among the reported details, so there is no independent numerical re-calculation to compare with the sponsor's result.

The registry record does not report the decision bounds or the sponsor's written conclusion about whether the planned equivalence criterion was met. The reported confidence interval can be described, but formal interpretation depends on the prespecified bounds. Since those are not available, the sponsor's estimate should be presented as reported, without inferring a pass or fail decision from the interval alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies Cmax of albendazole as the primary outcome and lists multiple secondary pharmacokinetic outcomes, including Cmax and area-under-the-curve measures for albendazole sulfoxide, area-under-the-curve measures for albendazole, time to Cmax, half-life, terminal elimination rate, and extrapolated area. It also lists the number of participants with treatment-emergent adverse events. The registry entries available do not include results for these secondary endpoints, apart from the safety counts discussed separately.

When many outcomes are analyzed, multiplicity can matter. General explanation: interpreting each endpoint as if it were the only analysis can raise the chance of a chance finding across the collection of tests. A protocol may specify a hierarchy, adjustment, or descriptive approach. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan detailed enough to determine how the secondary outcomes were handled. The primary result should not be taken as a summary of all listed outcomes.

Missing-data handling is also not reported in sufficient detail. The registry says the pharmacokinetic population included participants in the safety set who had at least one measurable pharmacokinetic assessment. It does not explain how missing time points, incomplete treatment periods, measurements outside assay limits, or participants with no measurable assessment were treated in each endpoint analysis. It also does not give reasons for the differences between the period-specific analysis counts.

The registry lists enrollment of 70 and separate period-specific counts of 64, 61, 63, and 62. Those counts describe the posted outcome rows and should not be summed to infer the number of participants. A participant flow account and the relationship among enrollment, safety, and pharmacokinetic analysis populations are not reported in the registry record. These omissions limit assessment of selection into the analysis population and whether missing observations could have affected the estimate.

The record does not report the study's sample-size justification, planned handling of interim analyses, or a complete statistical analysis plan. Those items cannot be inferred from the completed study status or from a planning illustration based on the observed effect.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (1.5%).

The registry reports serious adverse events by treatment group. In the test group, 1 participant was affected among 67 at risk; in the reference group, 0 were affected among 68 at risk. Deaths were 0 in both groups. The record lists appendicitis at 1.5% among the top serious-event terms, but does not establish in the registry record used which treatment group that term belongs to.

The registry also reports other events affecting 6 participants among 67 at risk in the test group and 6 among 68 at risk in the reference group. These counts are presented separately from serious events. They should not be conflated with the serious-event counts or interpreted as a complete description of event severity or clinical significance.

These are descriptive registry figures, not a powered comparative safety analysis. The record does not provide event definitions, event timing, severity beyond the serious-event classification, exposure-adjusted rates, or a statistical comparison between groups. The reported counts should therefore be read as the recorded event totals for the listed treatment groups, not as proof of a difference or equivalence in safety.

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

The result describes a pharmacokinetic comparison between Albendazole IP 400 mg and Albendazole 400 mg in healthy adults under fed conditions. For the primary endpoint, the registry reports a ratio of geometric least-squares means of 98.1 and a 90% confidence interval from 86.79 to 110.91. That result summarizes the relative Cmax estimate and its uncertainty within the reported analysis.

It does not, by itself, establish whether a formal bioequivalence criterion was satisfied. Such a conclusion depends on the acceptance limits specified before analysis and on the analysis plan. Those limits and the detailed model are not reported in the registry record. The result also does not show how the formulations compare on every secondary pharmacokinetic measure, because their numerical results are not included in the registry record.

The study is not a clinical-outcome trial in patients with intestinal disease. Participants are described as healthy adults, and the objective is to compare absorption of two formulations. Cmax is a pharmacokinetic endpoint, not a direct measure of symptom improvement, disease control, or clinical benefit. The registry record does not support conclusions about treatment effectiveness in a patient population.

The result also cannot establish that the formulations have identical effects in every individual. Group-level estimates and confidence intervals characterize an average model-based contrast, while individual responses can vary. The period-specific geometric coefficients of variation are large, but they do not reveal the distribution of paired within-participant differences. Nor do the posted counts provide a definitive comparative safety conclusion.

Thus, the most defensible interpretation is limited: the registry reports an estimated relative Cmax and its confidence interval from a randomized crossover study, together with descriptive period-specific summaries. Formal equivalence status, broader clinical implications, and the full interpretation of secondary outcomes cannot be determined from the registry record alone.

14. Why This Trial Matters Statistically

This trial illustrates why a bioequivalence result cannot be interpreted from treatment-group averages alone. The record gives geometric summaries for each period and a model-based ratio with a confidence interval. The latter is the central comparative estimate, while the former help describe the scale and variability of the observed concentrations. Keeping those quantities distinct prevents a descriptive comparison of means from being mistaken for the planned crossover analysis.

The replicated crossover design is also statistically important. Each participant was scheduled to receive both formulations more than once, in alternating orders. In general, repeated observations can help separate formulation differences from stable differences among participants, but they also make model structure and within-participant correlation important. The registry does not provide enough detail to reconstruct those features. This makes clear why marginal summaries cannot recreate an analysis that depends on paired observations.

The result highlights the role of prespecified equivalence limits. A ratio and confidence interval are not self-interpreting: an equivalence decision requires judging the interval against bounds established for the study. Those bounds are not reported in the registry record. Stating the estimate without claiming a formal pass or fail preserves the distinction between a numerical result and the decision rule that gives it meaning.

Finally, the record separates a pharmacokinetic primary endpoint from a broad list of secondary measures and safety outcomes. Without the secondary numerical results, multiplicity plan, missing-data rules, and analysis-population details, readers should avoid treating one reported estimate as a complete account of the study. This is a useful example of how registry results can offer a clear headline estimate while leaving important interpretive context unreported.

15. 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 principal limitation for interpretation is incomplete reporting of the statistical decision framework. The registry provides an equivalence estimate and a 90% confidence interval, but does not report the equivalence margins or detailed analysis model. This prevents independent verification of the formal equivalence conclusion and limits reproduction of the sponsor's result.

The record gives period-specific counts and summaries but does not provide participant-level data or within-participant covariance. In a crossover design, those relationships are relevant to the precision of the treatment comparison. The marginal geometric means and coefficients of variation cannot recover them. The registry also does not report how period, sequence, or carryover effects were handled, or the washout duration.

The PK population is described as participants in the safety set with at least one measurable assessment, but the registry does not provide detailed missing-data rules, reasons for absent measurements, or a full participant flow. Counts vary across the treatment-period rows. Those differences cannot be explained from the registry entries alone, and the period counts should not be combined to estimate the number of participants.

Numerical results for the listed secondary pharmacokinetic outcomes are not included in the registry record for this interpretation. The multiplicity approach, sample-size justification, and detailed statistical analysis plan are also not reported in the registry record. This leaves uncertainty about the broader outcome set and the original design rationale.

Finally, the study is described as open label and conducted in healthy adults under fed conditions. The registry record does not provide enough information to assess the implications of the absence of masking for laboratory processes or other study procedures. Its reported population and setting also restrict interpretation to the stated pharmacokinetic comparison, rather than clinical outcomes in patients.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bioequivalence Study Between Two Albendazole 400 mg Tablets in Healthy Adult Participants Under Fed Conditions — NCT06201559.
• Registry record last updated 2025-01-27; status last verified 2024-12.
• Results first posted 2025-01-27.
• 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.

19. Record Summary

The registry record describes a completed, randomized, open-label phase 1, four-period, two-sequence crossover study of Albendazole IP 400 mg and Albendazole 400 mg under fed conditions in healthy adult participants. Enrollment was 70. The primary outcome was maximum plasma concentration of albendazole, assessed using blood sampling and standard non-compartmental methods.

The primary reported equivalence analysis gives a ratio of geometric least-squares means of 98.1, with a 90% confidence interval from 86.79 to 110.91. Period-specific geometric means and geometric coefficients of variation are also reported for the first and second administrations of each formulation. The registry lists additional pharmacokinetic and safety outcomes, but their numerical results are not available in the registry record, apart from the adverse-event counts.

The registry record does not report the equivalence bounds, complete statistical model, multiplicity strategy, detailed missing-data handling, or sample-size justification. These omissions limit independent assessment of the formal equivalence decision and the full analysis context.