SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fast Admin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fast Admin (NCT01262989), a randomized phase 1 study. The primary outcome is AUC0-t.

2. Clinical Question

This is a formulation-comparison question in a controlled pharmacokinetic study, not a comparison of clinical outcomes in people with prostatic hyperplasia. Although that condition is listed in the registry, the described participants were healthy male volunteers. The record describes fasting administration and a two-period crossover: each participant received both the test and reference formulations, with the order determined by assigned sequence.

The primary outcome is AUC0-t, measured over the specified periods. The posted arm summaries give means and standard deviations for the completed-study population. A separate reported analysis gives the ratio of test formulation to reference formulation and its 90% confidence interval. The record does not state the prespecified equivalence limits, the detailed method for that reported ratio, or the rule used to make a formal bioequivalence decision. Therefore, the clinical question and the reported estimates can be described, but the formal decision criterion cannot be reconstructed from the registry record.

3. Trial Design

The registry describes a completed, randomized, open-label, two-treatment, two-sequence, two-period crossover study. It lists Phase 1 and 40 enrolled participants. The planned population was healthy male volunteers under fasting conditions. The record lists prostatic hyperplasia as a condition, but the participant description for the study and primary outcome is healthy volunteers rather than people being treated for that condition.

Participants followed one of two sequences. One sequence received the test product in Period 1 and the reference product in Period 2; the other received the reference product first and the test product second. The primary outcome timeframe is Days 1 to 3 for Period 1 and Days 9 to 11 for Period 2. The registry summary describes laboratory blinding, while the masking field is listed as none. It does not explain which study personnel were blinded or how laboratory blinding was implemented.

A crossover design allows each participant to receive both formulations, so the comparison can account for stable differences between participants when the analysis appropriately uses the paired observations. The registry’s posted arm summaries, however, present the formulations as separate groups with 35 participants in each, and the simple recalculation is an unadjusted comparison of those posted summaries. The detailed sponsor analysis method is not reported in the registry record.

The registry lists GlaxoSmithKline as sponsor and marks the study completed. It reports 40 enrolled, while the primary outcome population is participants who completed the study and the outcome summaries list 35 participants for each sequence. The reasons that participants did not appear in the primary outcome summaries are not reported in the registry record. The original design assumptions, including the planned sample-size justification, are also 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.

Period 1

Reasons for not completing this period:

7-Day Washout Period

Period 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who completed the study

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-t, measured over Days 1 to 3 (Period 1) and Days 9 to 11 (Period 2).

The primary endpoint is AUC0-t, expressed in ng per hour per ml (ng/h/ml). It represents the area under the plasma concentration-versus-time curve from time zero, before medication administration, until time t, the last quantifiable concentration. The registry says the area was calculated with the trapezoidal method: the areas between successive collection times and concentrations are added to estimate the curve’s total area.

AUC is used in pharmacokinetic research to estimate the extent of drug absorption and is useful for assessing bioavailability. In this study, it provides a quantitative measure for comparing the test and reference formulations after administration under fasting conditions. The endpoint is not a measure of symptom relief or a clinical outcome for prostatic hyperplasia.

The record gives the timeframe as Days 1 to 3 in Period 1 and Days 9 to 11 in Period 2. The primary outcome population is participants who completed the study. It reports means and standard deviations for the two formulations, as well as a test-to-reference ratio and a 90% confidence interval from the registry’s reported analysis. The record does not describe the complete pharmacokinetic analysis procedure or state the limits used to judge equivalence.

7. Results Posted in the Registry

• Test Product: mean 237.35 versus 226.74 on control; difference 10.61 (95% CI -40.75 to 61.97), standardized effect d = 0.10; z-test p = 0.686.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous, and the registry reports it as a mean with standard deviation. The primary comparison can be described in more than one way. A mean difference expresses the distance between two means on the endpoint’s original measurement scale. A ratio expresses one formulation’s value relative to the other. These measures answer related but different statistical questions and should not be treated as interchangeable.

What does the mean difference describe?

The posted means are 237.3 for the test product and 226.7 for the reference product. The recalculated unadjusted mean difference is 10.61. Its 95% confidence interval runs from -40.75 to 61.97. Because the interval includes zero, it includes values consistent with a difference in either direction as well as no difference on this scale. This description applies to the unadjusted recalculation; it does not establish a formal equivalence result.

The unadjusted p-value is 0.686. In general, a p-value measures how compatible observed data are with a particular null hypothesis under the assumptions of the test. It does not give the probability that the null hypothesis is true, and it does not quantify the probability that the formulations are equivalent. Here, the p-value belongs to the unadjusted recalculation, not to the ratio analysis reported by the registry.

Why does the crossover design matter?

In a crossover study, each participant receives both formulations, in an assigned order. Comparing the two measurements within each participant can remove some variation due to stable characteristics shared by that participant across periods. A paired analysis depends on the relationship between the two measurements from the same participant. Separate means and standard deviations do not reveal that relationship, so they do not contain all the information needed to reproduce a paired analysis.

The posted recalculation is explicitly an unadjusted comparison of the summary statistics. It is useful as a transparent descriptive calculation, but it does not use the participant-level pairing, sequence, or period information. The registry’s reported ratio analysis may use a method suited to the crossover design, but its method is not reported in the registry record. No specific model or adjustment should therefore be attributed to it.

What does the ratio and its interval mean?

The registry reports a test-to-reference ratio of 102.95 and a 90% confidence interval from 97.17 to 109.07. A ratio is a relative measure: it places the test formulation’s estimated value in relation to the reference formulation’s estimated value. A confidence interval describes uncertainty around an estimate under the analysis used. The interval does not, by itself, determine equivalence. That requires comparison with prespecified limits, which are not reported in the registry record.

The record labels the reported analysis as non-inferiority or equivalence, but does not give its method, a p-value, or the acceptance limits. Those omissions prevent a full assessment of how the label was operationalized. In particular, the ratio interval should not be judged against a conventional boundary unless that boundary is stated in the record.

How should variability be understood?

The standard deviations, 115.6 for the test product and 103.3 for the reference product, describe the spread of observed AUC values around their respective means. Standard deviation is a measure of variability among observations, not the precision of the estimated mean. Standard errors describe uncertainty in an estimate and depend on sample size and the analysis. The posted recalculation lists standard errors of 19.53 and 17.47 for the test and reference summaries, respectively.

In general, greater variability makes estimates less precise when other aspects of the study are held constant. In pharmacokinetic data, variability can affect the width of confidence intervals and the ability to assess a target range. The registry does not report participant-level observations, a within-participant variability estimate, or an explanation of how variability was handled in the sponsor’s analysis. Those details would be important for interpreting the crossover analysis beyond the summary statistics.

What can the recalculation establish?

A recalculation based on posted summary statistics is not necessarily the same as the trial’s prespecified primary analysis. It offers a check using a simple, unadjusted method and makes its assumptions visible. It does not recover information that is absent from the summaries, such as paired covariance, period effects, sequence effects, or participant-level exclusions. The registry does not report enough detail to determine how those features were addressed by the sponsor.

There is no discrepancy flagged between the reported and recalculated results. Even so, the recalculation and registry analysis remain different estimands and methods: one reports an unadjusted difference with a 95% confidence interval and p-value, while the registry reports a formulation ratio with a 90% confidence interval. The registry’s analysis is the relevant source for the sponsor’s stated result, while the unadjusted calculation is a supplementary view of the posted summaries.

10. Confidence Intervals and Precision

The registry’s reported ratio estimate is 102.95, with a 90% confidence interval from 97.17 to 109.07. The interval gives a range of values compatible with the data and the analysis used, subject to that analysis’s assumptions. It does not mean that there is a 90% probability that the true ratio lies within these particular limits. In general, confidence intervals describe the long-run performance of an interval-making procedure across repeated studies under its assumptions.

The interval’s interpretation depends on the statistical method, which is not reported in the registry record. It also depends on the decision limits specified for bioequivalence. Those limits are not reported, so the interval cannot be classified against the study’s formal criterion from the record alone. Its endpoints should be read as the uncertainty range reported for the ratio, not as a standalone declaration of equivalence.

The recalculated mean difference has a 95% confidence interval from -40.75 to 61.97. That interval is on the original AUC scale, whereas the registry’s 90% interval is for a ratio. The two intervals therefore answer different questions and use different confidence levels. The difference interval includes zero, but that observation is not a substitute for the ratio-based assessment used in a bioequivalence framework.

Precision is also influenced by the study’s design and analysis. The study is a crossover, but the unadjusted recalculation does not use participant-level pairing. The registry reports 35 participants in each treatment sequence for the primary outcome; it does not report the paired observations or the within-participant variability needed to independently assess the precision of a crossover estimate. The sponsor’s reported interval is therefore the available registry result for the ratio, while its statistical construction cannot be independently verified from the record.

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 illustrations based on the observed effect and are not the study’s original sample-size justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original trial design assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to provide an 80% chance of detecting the specified effect under those planning assumptions, if the assumptions hold. The 90% power column gives the corresponding number per arm for a higher chance of detection. These are planning targets, not observed results and not evidence that the completed study had a particular probability of success.

The rows describe planning for 100%, 75%, and 50% of the observed effect. The figures increase as the assumed effect becomes smaller: detecting a smaller effect generally requires more participants, all else being equal. The curve should be interpreted as a visual representation of this planning relationship under the stated assumptions; it does not add an independent estimate of the trial’s result.

These calculations are based on a simple two-arm planning framework, while the actual study used a two-period crossover. They should therefore be treated as illustrations rather than as a reconstruction of the trial’s design plan. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 10.610; pooled standard deviation σ = 109.620.
2. n = 2 × (1.96 + 0.842)² × 109.620² / 10.610² = 1,675.7, rounded up to 1,676 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 10.61                      # observed difference in means
sigma <- 109.620411420501                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1262989)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,676 (80% power), 2,244 (90% power)
 75% of observed effect: n per arm = 2,979 (80% power), 3,989 (90% power)
 50% of observed effect: n per arm = 6,703 (80% power), 8,974 (90% power)
power.t.test: 1676.6 
Simulated power at n = 1,676 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry’s own analysis reports a test-to-reference formulation ratio of 102.95 and a 90% confidence interval from 97.17 to 109.07. It labels the analysis as non-inferiority or equivalence, but does not report the statistical method, the acceptance limits, or a p-value. The registry does not provide enough information to determine the exact decision rule or reproduce that analysis.

The supplementary recalculation uses the posted means and standard deviations to estimate an unadjusted mean difference of 10.61, with a 95% confidence interval from -40.75 to 61.97 and an unadjusted p-value of 0.686. It is not the same analysis as the registry’s ratio result, and it does not use the participant-level pairing inherent in the crossover design. It should not be used to override the sponsor’s own analysis.

No discrepancy is flagged between the registry result and the recalculation. The two results remain different in scale, confidence level, and stated analysis. The sponsor’s reported ratio result takes precedence as the registry’s own analysis; the recalculation is a transparent, unadjusted check of the posted summary statistics rather than a replacement for the crossover analysis.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, with AUC0-t identified as the primary outcome. It lists no secondary outcomes posted. The record does not describe whether multiple outcomes, comparisons, or analyses were considered in a prespecified testing plan, or whether any multiplicity adjustment was planned or used. Without that information, the impact of multiple testing cannot be assessed.

The primary outcome population is described as participants who completed the study. The registry reports 40 enrolled and lists 35 participants for each treatment sequence in the primary outcome summaries. It does not explain the difference between enrollment and the outcome counts, identify reasons for non-completion, or describe how missing measurements were handled. No imputation method or sensitivity analysis for missing outcome data is reported in the registry record.

The crossover design also makes analysis-population details relevant. The record does not state whether the primary analysis included all participants who received treatment, only participants with complete data in both periods, or another defined population beyond the description of participants who completed the study. It does not report how protocol deviations, incomplete periods, or unusable concentration measurements were handled. These omissions limit assessment of potential selection effects and the reproducibility of the primary analysis.

The record identifies the reported ratio as a non-inferiority or equivalence analysis but does not report the detailed statistical plan, equivalence limits, handling of period or sequence effects, or rules for missing data. It also does not report interim analyses or a sample-size justification. These items should be treated as unreported rather than assumed absent or inferred from general practice. As a result, the registry supports a description of the posted estimates, but not a complete audit of the analysis plan or its execution.

15. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures are reported by treatment sequence. In the sequence receiving test product in Period 1 and reference product in Period 2, zero serious adverse events were reported among 20 participants at risk. In the sequence receiving reference product in Period 1 and test product in Period 2, zero serious adverse events were reported among 20 participants at risk.

These counts are sequence-level registry summaries. They do not provide a formulation-specific estimate of serious adverse events across periods, nor do they establish that no serious event occurred outside the reported observation or categorization. The deaths field is not populated, so deaths are not reported in the registry record. No serious adverse event terms are listed.

The record also lists other adverse events affecting 9 participants in the first sequence and 10 in the second sequence, each with 20 at risk. Those counts are separate from the serious adverse event figures and should not be conflated with them. The registry does not provide further details about event severity, timing by formulation, or attribution. These safety summaries describe what is posted for the study and are not a clinical safety recommendation.

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

The results describe a randomized crossover comparison of test and reference tamsulosin formulations in healthy male volunteers under fasting conditions. The primary endpoint, AUC0-t, is a pharmacokinetic measure of drug exposure over the period from administration to the last quantifiable concentration. It is used to compare the extent of absorption, not to measure symptom response or treatment outcomes for prostatic hyperplasia.

The posted means are 237.3 for the test product and 226.7 for the reference product. The registry’s own analysis reports a test-to-reference ratio of 102.95 with a 90% confidence interval from 97.17 to 109.07. These figures describe the observed estimates and their reported uncertainty. The registry does not state the equivalence limits, so the ratio interval cannot by itself establish whether a formal bioequivalence criterion was satisfied.

The unadjusted recalculation reports a mean difference of 10.61, with a 95% confidence interval from -40.75 to 61.97 and a p-value of 0.686. It uses summary statistics and does not account for the participant-level pairing of the crossover design. Its p-value is not a formal test of equivalence. A non-significant difference test is not proof that two formulations are equivalent.

The study was conducted in healthy male volunteers under fasting conditions. The findings therefore describe this study setting and population; the registry does not establish how the estimates apply to other populations or conditions. The record also does not provide the detailed sponsor method, the decision limits, or the handling of missing data needed for a complete independent evaluation. The results should be understood as registry-reported pharmacokinetic estimates, not as a conclusion about clinical benefit or a recommendation about treatment.

17. Why This Trial Matters Statistically

This study illustrates why the scale of an estimate matters. A mean difference and a formulation ratio both compare the test and reference products, but they answer the comparison on different scales. The mean difference is expressed in the endpoint’s units; the ratio expresses a relative comparison. Confidence intervals around these estimates must be interpreted according to their respective scales and analysis methods.

It also shows why a conventional difference test and an equivalence assessment are not interchangeable. A p-value of 0.686 from the unadjusted recalculation does not demonstrate equivalence. Equivalence requires a prespecified criterion and an analysis that evaluates whether the uncertainty range falls within that criterion. Although the registry reports a ratio and a 90% confidence interval, it does not report the limits needed to assess that decision.

The crossover design is statistically important. Each participant received both formulations, so paired data can carry information that separate treatment summaries do not preserve. A recalculation from the posted means and standard deviations is informative as a simple check, but cannot reproduce a participant-level crossover analysis. The registry’s limited methodological detail makes it important to distinguish the sponsor’s reported analysis from the unadjusted recalculation.

Finally, the gap between 40 enrolled and 35 participants listed per sequence for the primary outcome highlights the importance of analysis populations and missing-data reporting. Without reasons for exclusions or details of the analysis set, readers cannot fully assess how the available observations relate to enrollment. The record is useful for identifying the endpoint and posted estimates, while also demonstrating how omitted methods and decision limits constrain statistical interpretation.

18. 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 does not report the equivalence limits used for the ratio analysis, so the formal bioequivalence decision cannot be reconstructed. The method for the sponsor’s reported ratio, its handling of the crossover structure, and any model adjustments are not described. The confidence interval can be reported accurately, but its calculation cannot be independently checked from the registry record.

The unadjusted recalculation is limited by the summary-level information available. It does not use participant-level paired measurements, and the record does not provide within-participant covariance or individual concentration data. It therefore cannot reproduce a crossover analysis or evaluate possible period and sequence effects. The reported treatment summaries also do not explain how the two periods contributed to each participant’s endpoint.

The primary outcome population is participants who completed the study. The registry lists 40 enrolled and 35 participants in each sequence for the outcome, but does not report why the outcome summaries include fewer participants than were enrolled or how missing measurements were handled. It does not describe sensitivity analyses or other approaches to assess missing data.

The study population was healthy male volunteers under fasting conditions, which limits the scope of the setting described by the results. The registry does not report the original sample-size justification or detailed protocol assumptions. It also gives limited detail on blinding: the masking field says none, while the summary describes laboratory blinding. The responsibilities of blinded personnel are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fast Admin — NCT01262989.
• Registry record last updated 2017-08-14; status last verified 2017-07.
• Results first posted 2011-03-31.
• 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.

22. Record Summary

The registry describes a completed, randomized, open-label, two-period crossover study of test and reference tamsulosin hydrochloride 0,4 mg prolonged-release capsules in healthy male volunteers under fasting conditions. It lists 40 enrolled participants and identifies AUC0-t as the primary outcome, measured in participants who completed the study. The outcome summaries list 35 participants for each sequence.

The posted primary outcome means are 237.3 for the test product and 226.7 for the reference product. The registry’s reported analysis gives a test-to-reference ratio of 102.95 and a 90% confidence interval from 97.17 to 109.07. The unadjusted recalculation gives a mean difference of 10.61, a 95% confidence interval from -40.75 to 61.97, and an unadjusted p-value of 0.686.

The equivalence limits, sponsor analysis method, original sample-size justification, and missing-data procedures are not reported in the registry record. The estimates can therefore be described, but a formal equivalence decision cannot be independently verified from the posted information.