Bioequivalence Study of Telmisartan Between Telmisartan 80 mg/Amlodipine 5 mg FDC Tablet and Telmisartan 80 mg Tab and Amlodipine 5 mg Tab Concomitant Use: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study of Telmisartan Between Telmisartan 80 mg/Amlodipine 5 mg FDC Tablet and Telmisartan 80 mg Tab and Amlodipine 5 mg Tab Concomitant Use (NCT01344629), a randomized phase 1 study. The primary outcome is AUC0-tz.

2. Clinical Question

This is a pharmacokinetic comparison, not a trial of treatment for a health condition. Its stated aim is to investigate bioequivalence between two ways of administering the same listed doses. The primary endpoint concerns the amount of telmisartan measured in plasma over the observed interval, rather than a clinical outcome.

The crossover arrangement means that participants received treatments in multiple periods, according to randomized treatment sequences. That design allows within-participant comparison in principle, but the posted summary does not give the sequence-specific treatment results or enough detail to reconstruct the analysis. The central question is therefore limited to the registry’s reported exposure estimate and its uncertainty, not to clinical benefit or harm.

3. Trial Design

This was a phase 1, randomized, open-label study with a crossover model. Its official title describes a single-dose, four-period replicated crossover study in healthy male volunteers. The registry reports enrollment of 64 and lists the study as completed. The sponsor was Boehringer Ingelheim.

Participants received the fixed-dose combination tablet in one treatment condition and telmisartan and amlodipine as separate tablets taken together in the other. Both arms are described as using a single dose in a four-period replicated crossover design. A crossover study differs from a parallel-group study because participants can contribute observations under more than one treatment condition. This can make a within-participant comparison useful for pharmacokinetic questions, although the exact analysis depends on the protocol and statistical model.

The record gives the study start as 2011-04 and primary completion as 2011-07. It does not report the sequence allocation details, the timing or duration of any washout, or the precise conduct of each period. Those details should not be inferred from the word “crossover.” Randomization is reported, but the randomization method and concealment procedures are not reported in the registry record.

The primary endpoint is listed as AUC0-tz for telmisartan. Blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration. The record reports 126 observed pharmacokinetic parameter values for each treatment. These are period-level observations in a replicated crossover, not a count of 126 distinct participants per treatment.

Masking is listed as none, consistent with an open-label study. The registry record does not report a sample-size justification or the details of any interim analyses. The posted sample-size displays elsewhere on the page are planning illustrations based on the observed effect, not evidence of the trial’s original planning or of observed power.

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.

Crossover Period 1

Crossover Period 2

Reasons for not completing this period:

Crossover Period 3

Crossover Period 4

Analysis population for the primary outcome, as defined in the registry: One subject who discontinued the study on period 2 was excluded from Pharmacokinetic data set. Therefore, the number of observed PK parameter were 32+32+31+31=126 in T80/A5 FDC tablet and T80 + A5, respectively.

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 AUC0-tz, measured over Serial pharmacokinetic blood samples collected before drug administration, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after drug administration.

The primary endpoint, AUC0-tz, is the area under the plasma concentration-time curve for telmisartan from time zero to the time of the last quantifiable data point. It summarizes measured drug exposure across the sampled interval. The unit is ng*hour/mL, and the registry reports the treatment summaries as geometric means with geometric coefficients of variation.

AUC is used in pharmacokinetic comparisons because it incorporates concentration measurements across time rather than relying on a single blood sample. In general, two formulations can have similar exposure summaries even if their concentration profiles differ at particular sampling times; other pharmacokinetic measures can help describe those patterns. The registry lists AUC0-∞, Tmax, λz, t1/2 and MRTpo as secondary outcomes, but their result values are not included in the registry record.

The posted primary analysis gives a test/reference ratio of the mean, multiplied by 100, and a 90% confidence interval. In general, the ratio expresses the relative exposure estimate for the treatments, while the interval describes uncertainty around that estimate under the stated analysis. Judging bioequivalence also requires a prespecified acceptance range. The registry record does not report that range, so the interval alone cannot establish whether a formal bioequivalence criterion was met.

The endpoint is a laboratory-based pharmacokinetic measure, not a direct measure of symptoms, disease control, or other clinical outcomes. Its interpretation should remain tied to the question of relative telmisartan exposure in this study population and under this single-dose study design.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary comparison is reported as an ANOVA, with the parameter described as the test/reference ratio of the mean multiplied by 100. The registry reports the result as a ratio estimate and a 90% confidence interval. It does not provide enough detail to reproduce the model or to verify which terms were included in it.

What the ratio describes

In general, a ratio places one treatment’s mean relative to another treatment’s mean. A value expressed as a percentage uses 100 to represent equality of the two quantities being compared. Here, the posted estimate is 100.9 for the test/reference comparison. The treatment labels in the record identify the fixed-dose combination and the concomitant tablets, but the registry does not provide a fuller model specification or an independent derivation of the estimate from participant-level data.

The arm summaries are geometric means, a common way to describe positive pharmacokinetic measurements that can be skewed. In general, geometric means are calculated on a logarithmic scale and then expressed on the original scale. That approach can make relative comparisons more natural for exposure data. The record reports geometric coefficients of variation as measures of dispersion. In general, a coefficient of variation summarizes variability relative to the scale of the measurements; the geometric version is associated with the geometric-data analysis. It should not be confused with the uncertainty interval for the ratio.

How to read the confidence interval

The 90% confidence interval runs from 97.7 to 104.2. In general, a confidence interval describes the precision of an estimate under a specified statistical procedure: narrower intervals indicate greater precision than wider intervals on the same scale. It is not a guarantee that the true value lies inside this particular interval, and it does not by itself give the probability that a treatment comparison is equivalent.

For a formal equivalence assessment, the interval is interpreted against acceptance bounds set in advance. If the full interval meets the specified bounds, that can support an equivalence conclusion under the trial’s planned method. The registry record does not report those bounds, so this page cannot apply that decision rule. The interval should therefore be read as the posted uncertainty around the ratio, rather than as a stand-alone pass-or-fail result.

Why crossover structure matters

In general, crossover designs compare treatments within participants, which can reduce the influence of stable differences between individuals. A replicated crossover also obtains repeated period observations for treatments. Correct analysis needs to account for the design and the dependence among observations from the same participant. Treating every period observation as if it came from a different person would generally misrepresent the amount of independent information.

The registry reports 32+32+31+31=126 observed pharmacokinetic parameters for each treatment and says one participant discontinued during period 2 and was excluded from the pharmacokinetic data set. The record does not describe the fitted ANOVA model, the treatment sequence structure, participant effects, period effects, or any other model terms. It is therefore not possible to assess from the registry summary whether each design feature was handled in a particular way. The reported sponsor analysis remains the available inferential result.

What over-dispersion can mean

In general, over-dispersion means that the observed variability is greater than a statistical model would expect under its assumptions. It matters because standard errors and confidence intervals can be too optimistic if the model understates variation. The geometric coefficients of variation posted describe variability, but their presence alone does not show that over-dispersion occurred or that the analysis failed. Assessing model fit would require diagnostic information that is not reported in the registry record.

Recalculation and planning displays

The calculated material may include simple unadjusted recalculations from posted summary statistics where a two-arm comparison can be reduced to one comparison. Here the record identifies the analysis kind as “other,” and the calculation system indicates that values are missing or not estimable for such a comparison. The posted ANOVA result is therefore the main reported inferential comparison; it should not be replaced by an unadjusted reconstruction that the available summaries cannot support.

In general, sample-size planning illustrations show how many participants per arm a hypothetical future study might require under chosen assumptions. The illustrations described for this page use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. They are planning scenarios, not the original trial’s design justification and not “observed power.” The registry record does not report the original sample-size justification.

10. Analyses Reported by the Sponsor

The registry posts an ANOVA result for the primary comparison: a test/reference ratio of 100.9 and a 90% confidence interval from 97.7 to 104.2. The arm-level geometric means and geometric coefficients of variation provide descriptive context, but they do not reproduce that analysis by themselves. The crossover structure and the model used for the sponsor’s comparison matter to the estimate and its uncertainty.

No discrepancy is flagged between the posted analysis and any recalculated result. In this record, a separate unadjusted recalculation is not available for the two-arm comparison because the analysis is identified as “other” and the relevant values are not estimable from the posted summaries. The sponsor’s listed analysis is consequently the appropriate result to describe, rather than an independently reconstructed comparison.

The record does not report a p-value, the model specification in detail, or the equivalence limits. The ratio and interval can be quoted, but a formal conclusion about meeting a bioequivalence criterion cannot be independently checked without the decision limits and associated analysis details. The sponsor’s result should be presented as the registry reports it, with those limits of interpretation made clear.

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is AUC0-tz. The registry also lists five secondary outcomes: AUC0-∞, Tmax, λz, t1/2 and MRTpo. It reports seven outcome measures and seven analyses overall. Those registry counts do not explain how the analyses map to each listed outcome, and the numerical results for the secondary outcomes are not reported in the record.

When several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control that risk, but they depend on which outcomes were planned, how they were ordered, and what adjustment was prespecified. The registry record does not report whether any multiplicity adjustment was planned or used. There is no basis to infer that the primary analysis was adjusted, or that the secondary analyses were confirmatory.

The record says one subject who discontinued during period 2 was excluded from the pharmacokinetic data set. It gives observed pharmacokinetic counts as 32+32+31+31=126 for each treatment. These are observations across periods in a crossover design; they should not be read as participant counts per arm in a parallel-group trial. The record does not explain any imputation method, how other incomplete measurements were handled, or whether sensitivity analyses were conducted.

The analysis population is described as a pharmacokinetic data set, but formal population labels such as intention-to-treat or per-protocol are not reported in the registry record. The reasons for excluding the participant and any prespecified rules for exclusions beyond this statement are not described. The record also does not report a missing-data analysis plan or the extent of missingness at individual sampling times. These omissions limit independent assessment of the analysis population and the robustness of the result, but they do not justify assuming that additional exclusions or adjustments occurred.

12. 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 posted serious adverse event figures are grouped by treatment sequence. For Treatment Sequence A, the record lists 32 at risk and 0 affected for serious adverse events, and 32 at risk and 0 affected for other adverse events. For Treatment Sequence B, it likewise lists 32 at risk and 0 affected for serious adverse events, and 32 at risk and 0 affected for other adverse events.

These are the registry’s reported counts for the listed groups. Because this was a crossover study, a treatment sequence is not the same thing as a separate treatment arm in a parallel-group design. The summary does not provide event narratives, timing, exposure-specific counts, or information about how adverse events were attributed across periods. It should not be used to infer more detail than the displayed figures contain.

Deaths are shown as not reported in the registry record. Zero affected in these summary rows does not establish that no events of any kind occurred under every possible definition or observation window. The record does not give enough detail about adverse-event collection duration or the safety analysis population to broaden the interpretation. These figures describe the posted summaries; they are not a comparative safety assessment.

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

The posted result addresses a narrow question: how telmisartan exposure, as measured by AUC0-tz, compared after a single dose of the fixed-dose combination tablet and after the two component tablets were taken together in this study. The reported test/reference estimate is 100.9, and its 90% confidence interval is 97.7 to 104.2. This gives a point estimate and an interval for the relative exposure comparison.

It does not, by itself, establish whether a formal bioequivalence criterion was met. That requires the prespecified acceptance limits and the planned analysis; the registry record does not report the limits. The posted summary also does not include a p-value. A conclusion should not be based solely on the fact that the estimate is near 100 or on a visual reading of the interval without the applicable decision boundaries.

Nor does the comparison test clinical effectiveness or establish comparative safety. The endpoint is a pharmacokinetic measure, and the study involved healthy male volunteers under a single-dose design. The posted results do not establish what would happen with repeated dosing, in other populations, or on clinical outcomes. The registry record lists several secondary pharmacokinetic outcomes, but their numerical results are not available.

The reported geometric means and coefficients of variation describe the observed exposure summaries, while the ratio and confidence interval describe the formal comparison. The crossover design means the observations are collected over periods and should not be interpreted as independent participant counts for each treatment. One participant who discontinued during period 2 was excluded from the pharmacokinetic data set, and the record does not describe additional missing-data handling.

Thus, the result is best understood as a posted estimate of relative telmisartan exposure with a stated interval, in a particular study population and design. It is not a general claim about patient outcomes, nor is it enough on its own to verify a regulatory or protocol-defined equivalence decision.

14. Why This Trial Matters Statistically

This study illustrates why the statistical interpretation of a bioequivalence comparison cannot rest on the two treatment means alone. The geometric means, 1970.0 ng*hour/mL and 1950.0 ng*hour/mL, summarize the observed AUC0-tz values. The ratio and confidence interval give the comparative estimate and its uncertainty. Each answers a different descriptive question.

The crossover structure is also important. Participants contribute observations across treatment periods, so the number of recorded pharmacokinetic observations is not the number of independent participants per treatment. A valid analysis needs to reflect the repeated, within-participant structure. The registry reports an ANOVA comparison but does not give enough model detail to reproduce or fully assess it from the summary.

The example also shows why confidence intervals need a decision context. An interval can be reported precisely, but a formal bioequivalence judgment depends on boundaries defined in advance. Since those limits are not reported in this record, readers should distinguish the numerical estimate from a conclusion about whether a criterion was satisfied.

Finally, the record separates what is measured from what is clinically important. AUC0-tz describes telmisartan exposure after a single dose; it is not a symptom or clinical outcome. The study’s specific design and population define the scope of the result. These distinctions are useful when reading pharmacokinetic trials more broadly: identify the estimand, the analysis structure, the uncertainty, and the decision rule before drawing a conclusion.

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 available record leaves several trial-specific details unclear. Although it identifies a randomized, open-label, four-period replicated crossover design, it does not report the treatment sequence allocation details, washout arrangements, or the full ANOVA model. Those details matter for understanding the handling of period and participant effects, but they cannot be reconstructed from the summary.

The primary endpoint is reported with an estimate and a 90% confidence interval, but the equivalence margins are not reported. The registry record therefore does not give the complete decision framework needed to verify a formal bioequivalence conclusion. The p-value is also not reported. The stated endpoint summaries cannot substitute for these missing inferential details.

The pharmacokinetic data set excluded one participant who discontinued during period 2. The record does not specify the detailed exclusion criteria, the treatment-period observations retained for that participant, or the handling of any missing samples. It does not report sensitivity analyses or other checks of robustness. The listed secondary outcomes lack numerical results in the material, limiting assessment beyond the primary endpoint.

The study population was healthy male volunteers, and the study used a single-dose design. These features constrain interpretation to the setting described; the result does not answer questions about repeated dosing, other populations, or clinical outcomes. The registry reports no masking, so the study was open-label, although the primary endpoint is based on measured plasma concentrations.

Safety information is summarized by treatment sequence, without event narratives or details on observation periods. Death counts are not reported in the registry record. Finally, the registry record does not report the original sample-size justification or interim-analysis plan. Planning illustrations based on the observed effect cannot fill those gaps or describe the trial’s original design rationale.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bioequivalence Study of Telmisartan Between Telmisartan 80 mg/Amlodipine 5 mg FDC Tablet and Telmisartan 80 mg Tab and Amlodipine 5 mg Tab Concomitant Use — NCT01344629.
• Registry record last updated 2014-03-28; status last verified 2014-02.
• Results first posted 2012-08-27.
• 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

This completed phase 1 study compared telmisartan 80 mg/amlodipine 5 mg as a fixed-dose combination tablet with telmisartan 80 mg and amlodipine 5 mg taken concomitantly. It was randomized, open-label and described as a single-dose, four-period replicated crossover study in healthy male volunteers. Enrollment was 64.

The primary endpoint was telmisartan AUC0-tz. The posted ANOVA result is a test/reference ratio of 100.9 with a 90% confidence interval from 97.7 to 104.2. The record does not report the equivalence limits needed to assess a formal bioequivalence decision. One participant who discontinued during period 2 was excluded from the pharmacokinetic data set, and observed pharmacokinetic counts were 126 for each treatment.

The record lists secondary pharmacokinetic outcomes but does not include their numerical results. It reports no affected participants for the displayed serious and other adverse-event rows; deaths are not reported in the registry record. The result should be read as a single-dose exposure comparison, not as a clinical-outcome or broad safety assessment.