Clarithromycin 500 mg Extended Release Tablets Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clarithromycin 500 mg Extended Release Tablets Under Fasting Conditions (NCT00840411), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration.

2. Clinical Question

The comparison concerns measured drug concentration after administration of the two formulations, rather than a clinical health outcome. The posted primary results give a mean Cmax of 640.1 ng/mL for each treatment group and a sponsor-reported test-to-reference ratio of LS means x 100 of 100.0, with a 90% confidence interval from 93.3 to 107.1. The registry also posts an unadjusted mean-difference recalculation with a confidence interval that spans values below and above zero. These are different summaries and should not be treated as interchangeable.

The study record identifies healthy subjects, fasting conditions, and a single-dose comparison. It does not report a patient population or outcomes beyond the stated drug-concentration measures in the material described by this record.

3. Trial Design

This was a randomized, two-way crossover, single-dose, open-label study. The two treatment conditions were clarithromycin ER 500 mg tablets and BIAXIN® XL 500 mg tablets. In a crossover design, participants receive both treatments in an assigned order, so each participant can contribute measurements under both conditions. Randomization concerns assignment to treatment order; the registry identifies the two sequences as Clarithromycin (test) First and Biaxin® XL (reference) First.

The study was conducted in 66 fasted, healthy, adult subjects according to its official title and brief summary. The posted primary outcome analysis includes data from subjects who completed the study. The outcome listings report 62 participants for each treatment. The record does not give further details about withdrawals or why the completion-based analysis included fewer participants than planned enrollment.

The study is identified as Phase 1 and completed. The registry lists the start as 2002-09 and primary completion as 2002-10. The design was open-label, meaning the record does not indicate masking of participants or study personnel. It does not report the treatment sequence allocation details, the interval between treatment periods, washout procedures, or other operational features beyond the stated crossover design.

The primary outcome was Cmax, measured in ng/mL from blood samples collected over a 36 hour period. The registry lists three outcome measures and three analyses, but the material described for the primary outcome does not provide the other outcome results. The original design assumptions, including any planned sample-size justification or prespecified analysis details, 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.

First Intervention

Reasons for not completing this period:

Washout

Reasons for not completing this period:

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Data from subjects who completed the study were included in the statistical analysis.

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 Cmax - Maximum Observed Concentration, measured over Blood samples collected over 36 hour period.

The primary endpoint is Cmax, the maximum observed concentration of clarithromycin in blood following administration. It is a continuous measure reported in ng/mL. For each treatment, the posted results give a mean and standard deviation. Blood samples were collected over a 36 hour period, and the endpoint description identifies bioequivalence based on Cmax.

Cmax is useful in a relative-bioavailability comparison because it describes the highest measured concentration reached during the sampling period. Comparing this measure across formulations helps characterize whether the test and reference products produce similar concentration profiles at their observed peaks. It is not, by itself, a measure of clinical benefit or harm, and it does not describe the full concentration-time profile. Other pharmacokinetic measures may address different features, but their results are not included in the primary outcome details presented in this record.

The registry reports the same displayed mean Cmax, 640.1 ng/mL, for clarithromycin and Biaxin® XL, while the standard deviations are 214.2 and 231.8, respectively. The sponsor’s posted comparison uses a ratio of LS means, whereas the separate recalculation expresses the contrast as a mean difference. These summaries answer the comparison in different scales. The registry does not report the bioequivalence acceptance limits, so the endpoint values alone do not establish whether a prespecified equivalence criterion was met.

7. Results Posted in the Registry

• Biaxin® XL: mean 640.11 versus 640.08 on control; difference 0.03 (95% CI -78.53 to 78.59), standardized effect d = 0.00; z-test p = 0.999.

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical summaries use two different scales for comparing Cmax. The sponsor-reported result is a ratio of least-squares means multiplied by 100. The separate recalculation is an unadjusted difference between arithmetic means. A ratio describes the test result relative to the reference result, while a difference describes the amount by which one mean exceeds or falls below the other in the endpoint’s units. Because the scales and methods differ, their estimates and confidence intervals should be interpreted separately rather than combined into one result.

What does the mean describe?

The mean is a measure of the central value of the observed Cmax measurements. The reported mean is 640.1 ng/mL for each treatment. Equal displayed means indicate equality at the precision shown, not necessarily identical underlying participant values. Individual measurements can vary even when group averages match. The registry also reports standard deviations, which describe the spread of observations around their group means. The standard deviations are 214.2 for clarithromycin and 231.8 for Biaxin® XL.

What is a ratio of least-squares means?

A least-squares mean is a model-based estimate of a group mean. The registry reports the test-to-reference ratio of LS means x 100 as 100.0. On this scale, 100.0 corresponds to equal estimated means. The associated 90% confidence interval is 93.3 to 107.1. The record does not name the statistical model or give details of any adjustment, so the exact model-based procedure cannot be reconstructed from the outcome entry. In particular, the label alone does not establish which terms, if any, were included in the sponsor’s model.

Why is a crossover analysis different?

In a crossover study, the same participant receives both treatments in an assigned sequence. Comparing measurements within a participant can account for stable differences between people and uses the pairing of observations. A standard independent-group comparison does not use that pairing. The unadjusted recalculation presented for this outcome is a simple comparison of posted summary statistics and does not fully represent the crossover structure. The registry does not provide the paired treatment differences or the within-participant correlation needed to reconstruct a paired estimate from these summaries.

Sequence and period effects can also matter in crossover analyses: sequence refers to treatment order, and period refers to the treatment occasion. The registry record does not report whether or how these effects were modeled, nor does it describe a washout interval. These omissions prevent a detailed assessment of the sponsor’s crossover model. They do not change what the posted summary statistics state, but they limit independent replication of the primary analysis.

What does the recalculated p-value mean?

The unadjusted recalculation reports a mean difference of 0.03 and p = 0.999, with a 95% confidence interval from -78.53 to 78.59. A p-value measures how compatible the observed result is with a specified null model, under the assumptions of that analysis. It is not the probability that the treatments are equal, and it does not quantify the probability that a conclusion is correct. Because this recalculation is unadjusted and does not use the crossover pairing, the p-value should not be substituted for the sponsor’s reported bioequivalence analysis.

Why do equivalence questions need a margin?

In an equivalence assessment, the question is whether the plausible treatment difference is contained within prespecified limits judged acceptable for the purpose of the study. A confidence interval is interpreted relative to those limits. A ratio confidence interval that includes 100.0 shows that equality is among the values compatible with the estimate, but that fact alone does not demonstrate equivalence. The registry record does not report the limits or the detailed decision rule, so the posted ratio and interval cannot be used to verify the criterion.

General statistical context: confidence intervals reflect sampling uncertainty under the analysis assumptions, while standard deviations describe variation among observed measurements. Neither summary accounts automatically for design features omitted from the calculation. In a crossover trial, preserving the participant-level pairing is particularly relevant to the precision of a treatment contrast. The registry reports the sponsor’s ratio result and a separate unadjusted recalculation, but does not provide enough model detail or paired data to reproduce a full crossover analysis.

10. Confidence Intervals and Precision

The sponsor-reported estimate is a test-to-reference ratio of LS means x 100 of 100.0, with a 90% confidence interval from 93.3 to 107.1. The interval describes a range of values compatible with the observed data and the sponsor’s analysis assumptions. Its center is the reported estimate, and its span conveys uncertainty: values below and above 100.0 remain compatible with the estimate at the stated confidence level.

The registry does not state the equivalence margins. Consequently, the interval cannot be assessed against the study’s decision limits from this record. A confidence interval that includes the ratio value 100.0 is not, by itself, proof of equivalence. For an equivalence conclusion, the interval must be compared with prespecified acceptable boundaries, and those boundaries are not reported in the registry record.

The separate unadjusted recalculation gives a mean difference of 0.03, with a 95% confidence interval from -78.53 to 78.59. This interval includes zero and allows for differences in either direction. It uses a different contrast scale and a different confidence level from the sponsor’s ratio result, so its numerical limits should not be compared directly with the sponsor’s ratio limits. It also does not account for the participant-level pairing inherent in the crossover design.

The registry reports 62 participants for each treatment in the primary outcome summary. The precision of a crossover treatment comparison depends not only on the number of participants but also on the variability and correlation of paired measurements. Those paired details are not reported. The displayed confidence intervals therefore provide the uncertainty summaries associated with their respective reported analyses, not a complete independent reconstruction of precision under the trial design.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are an illustration based on the observed effect rather than the trial’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and those assumptions were correct. The 90% power column gives the corresponding illustration for a 90% chance. Power is a property of a planned analysis under assumed conditions; it is not a measure of whether the observed study result is true.

The listed rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller target effects are harder to distinguish from sampling variability and therefore require more participants under the same assumptions. In this outcome, the observed recalculated mean difference is very small relative to the reported variability, so the resulting illustrations are extremely large. They should not be read as a recommendation or as the trial’s actual enrollment target.

This is not observed power. It is a planning illustration derived from the observed effect and the stated generic assumptions; it does not establish how well the completed trial was designed or what its original power was.

12. How the Sample Size Is Derived

13. Analyses Reported by the Sponsor

The sponsor’s posted result is a test-to-reference ratio of LS means x 100 of 100.0, with a 90% confidence interval from 93.3 to 107.1. This is the study’s reported ratio-scale analysis. The registry does not identify the model in the result entry or provide enough detail to reproduce it independently. The record also does not give the equivalence margins needed to assess the interval against a prespecified bioequivalence decision rule.

The separate recalculation uses posted group summaries to estimate an unadjusted mean difference of 0.03, with a 95% confidence interval from -78.53 to 78.59 and p = 0.999. It is not the sponsor’s analysis: it uses a difference rather than a ratio, has a different confidence level, and does not represent the crossover pairing as a paired treatment contrast. It is best viewed as a simple check of the displayed summary means, not as a substitute for the sponsor’s analysis.

The registry record does not flag a discrepancy between the reported and recalculated results. The sponsor’s result remains the relevant posted analysis for the trial’s stated bioequivalence objective, while the recalculation offers a limited unadjusted summary. Neither result can be interpreted against the study’s equivalence criterion without the unreported margins and further analysis details.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but the primary outcome details identify Cmax and the posted material described for this result does not provide the other outcomes or their results. Whether the trial prespecified a hierarchy among outcomes, adjusted for multiple comparisons, or used a particular strategy to control the chance of false-positive findings is not reported in the registry record. No multiplicity adjustment should be inferred from the number of listed measures alone.

The primary endpoint’s analysis population is described as subjects who completed the study. The outcome summary reports 62 participants for each treatment, while planned enrollment was 66. The registry does not report the reasons for non-completion, the timing of missing measurements, or whether any additional participants or observations were excluded. It also does not describe how missing data were handled. Because the primary analysis is completion-based, the record does not establish whether all randomized participants contributed to the primary endpoint analysis.

The record describes a randomized, two-way crossover trial, but does not provide a detailed statistical analysis plan. The specific model, treatment of period and sequence effects, handling of carryover concerns, and use of participant-level pairing are not reported in the registry record. The sponsor’s result is identified as a ratio of LS means, but that label alone is insufficient to determine the full model specification.

The posted analysis category indicates a legacy non-inferiority or equivalence analysis. However, the equivalence margins, any prespecified testing sequence, and the decision rule are not reported. The record also does not state whether interim analyses were planned or performed. These omissions limit assessment of multiplicity, missing-data handling, and the complete analysis population. They do not change the reported Cmax summaries, but they prevent a full audit of the analysis decisions underlying them.

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

The results describe Cmax after a single dose of test clarithromycin extended-release tablets and Biaxin® XL in fasted, healthy adult subjects. The displayed mean Cmax is 640.1 ng/mL for both treatments. The sponsor reports a ratio of LS means x 100 of 100.0, with a 90% confidence interval from 93.3 to 107.1. These figures describe the measured concentration comparison and its reported uncertainty in this study.

They do not, by themselves, show that a prespecified bioequivalence standard was met. A formal equivalence assessment depends on the margins and decision rule, which are not reported in the registry record. Nor does the unadjusted recalculation establish equivalence: its mean-difference confidence interval spans -78.53 to 78.59 and is not a substitute for the sponsor’s crossover analysis.

The endpoint is a pharmacokinetic measure, not a patient-centered clinical outcome. The trial record concerns healthy subjects under fasting conditions and a single-dose comparison. The results therefore do not directly describe clinical outcomes, repeated dosing, fed conditions, or other populations. The registry record does not provide results that would support conclusions about those circumstances.

The data also do not establish that either product is clinically preferable or that treatment should be selected on the basis of these results. The appropriate interpretation is limited to the reported concentration summaries and the analysis context that is available. The absent equivalence margins and incomplete model details leave important parts of the formal bioequivalence assessment unresolved in the registry record.

16. Why This Trial Matters Statistically

This study illustrates why the design and statistical contrast must be considered together. In a crossover trial, participants receive both formulations, making the within-participant comparison central to the design. A simple difference between group means does not retain all of that paired information. The registry’s recalculated result is therefore useful as a limited summary check, but it should not be mistaken for a complete crossover analysis.

It also demonstrates that equal displayed means and a ratio estimate of 100.0 do not, on their own, settle an equivalence question. Equivalence requires a confidence interval to be assessed against prespecified boundaries. Without those margins, readers can describe the estimate and its uncertainty but cannot verify the formal decision criterion from the registry record.

The endpoint and population also define the scope of inference. Cmax captures the maximum observed concentration during the stated sampling period; it is not a clinical outcome and does not describe every aspect of exposure. The study’s fasting, healthy-subject, single-dose setting matters when interpreting what the results address.

Finally, the contrast between the sponsor’s ratio-scale result and the simple unadjusted mean-difference recalculation is a useful reminder that a recalculation is not automatically a replication. The analysis scale, crossover structure, model details, missing-data handling, and decision margins all affect how a result should be read. Transparent reporting of these elements makes it possible to evaluate both the estimate and the inference drawn from it.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the equivalence margins or the complete decision rule. This is a central limitation for interpreting an analysis labeled as non-inferiority or equivalence: the sponsor’s ratio interval cannot be compared with the intended acceptance boundaries from the record alone.

The reported sponsor method is identified as a ratio of LS means, but the model specification is not reported. The record does not explain how the crossover pairing, treatment period, or treatment sequence was handled. It also does not report the washout interval or other details that would allow readers to evaluate potential carryover concerns.

The primary analysis included subjects who completed the study, and the posted summaries report 62 participants for each treatment compared with planned enrollment of 66. Reasons for non-completion, missing measurements, and any exclusions are not reported in the registry record. The record does not describe sensitivity analyses or methods for handling missing data.

The independent recalculation is unadjusted and does not use the paired participant-level data needed to reconstruct a crossover treatment contrast. The participant-level observations and within-person correlation are not reported. The primary Cmax result is available, but the other listed outcome measures and their results are not described in the outcome details.

The study was open-label and involved healthy, fasted adult subjects receiving a single dose. The registry does not report masking, and the design does not provide direct evidence about clinical outcomes or other dosing conditions. These boundaries should remain part of any interpretation of the posted pharmacokinetic comparison.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clarithromycin 500 mg Extended Release Tablets Under Fasting Conditions — NCT00840411.
• Registry record last updated 2024-08-19; status last verified 2024-08.
• Results first posted 2009-07-21.
• 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.

21. Record Summary

The registry record describes a completed Phase 1 randomized, open-label, two-way crossover, single-dose comparison of clarithromycin ER 500 mg tablets with BIAXIN® XL 500 mg tablets in fasted, healthy adult subjects. Planned enrollment was 66.

The primary outcome was Cmax in ng/mL, based on blood samples collected over a 36 hour period. The primary analysis included data from subjects who completed the study; the treatment summaries report 62 participants each. The mean Cmax was 640.1 for both treatments.

The sponsor-reported test-to-reference ratio of LS means x 100 was 100.0, with a 90% confidence interval from 93.3 to 107.1. A separate unadjusted mean-difference recalculation was 0.03, with a 95% confidence interval from -78.53 to 78.59. The registry does not report the equivalence margins, complete model details, or original sample-size assumptions.