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

1. Trial at a Glance

This page covers the registry results for SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fed Admin (NCT01330303), a randomized phase 1 study. The primary outcome is AUC 0-t.

2. Clinical Question

This is a formulation comparison in a controlled study setting, rather than a comparison of treatment strategies or clinical outcomes. The endpoint concerns drug concentration over time; it does not directly measure symptoms, disease progression, or a clinical benefit. The registry record reports randomization and a crossover design, with two treatment sequences. Each participant was intended to receive both formulations, one in each period, under fed conditions. That structure allows the comparison to use within-participant information, although the posted group-summary re-calculation does not preserve the paired structure. The record does not report a separate clinical-effectiveness question.

3. Trial Design

The study is identified as NCT01330303 and titled SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fed Admin. It is listed as a Phase 1, randomized, open-label crossover study. The registry describes two treatments, two sequences, and two periods. In each period, participants received either the test or reference formulation under fed conditions. One sequence received the reference drug followed by the test drug; the other received the test drug followed by the reference drug.

The planned crossover structure is important to interpretation. Each participant could contribute observations under both formulations, so treatment comparisons may be made within participants rather than treating the formulation groups as unrelated samples. The ordering of treatment was randomized, and having two sequences allows the reverse order to be represented. The record does not report details of the randomization procedure, allocation concealment, a washout interval, or how period and sequence effects were handled in the primary analysis.

The study is listed as completed, with enrollment of 37. The recorded start date is 2009-12-08, and the primary completion date is 2009-12-22. The sponsor is GlaxoSmithKline. Masking is listed as none, while the brief description says the study was open-label and laboratory-blind. Thus, participants and study personnel were not described as masked, but laboratory blinding was reported. The record does not explain which laboratory staff were blinded or how that blinding was implemented.

The primary outcome is AUC 0-t among participants who completed the study. The registry lists 37 participants for each formulation summary, while the safety sequence groups each list 20 at risk. These figures describe different posted summaries; the record does not explain how the group counts relate to enrollment or reconcile them. The number of outcome measures and analyses is listed as three each, but further results for secondary outcomes are not posted. The trial's original sample-size justification and the details of its prespecified statistical plan 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.

Period 1

Reasons for not completing this period:

7-Day Washout Period

Period 2

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 AUC 0-t, measured over Day 1 (day that blood collections started) to Day 4 (Period 1) and Days 8 to 11 (Period 2).

The primary endpoint, AUC 0-t, measures the area under the curve formed by plasma drug concentration over time, beginning at time zero before administration and ending at the last quantifiable concentration. The registry says the area was calculated using the trapezoidal method: areas between successive collection times and concentrations are added. The reported unit is ng per hour per ml (ng.h/ml).

AUC is used in pharmacokinetic research as an indicator of the extent of drug absorption, or overall systemic exposure during the measured interval. Comparing AUC for two formulations can therefore address whether the amount of drug exposure is similar under the conditions studied. In this trial, that comparison concerns the test formulation and SECOTEX® reference formulation after administration under fed conditions.

The endpoint is a continuous measure. The registry reports means and standard deviations for each formulation, as well as a test-to-reference ratio with a 90% confidence interval. These are different ways to express the comparison: the means retain the endpoint's concentration-time units, while the ratio expresses relative exposure. AUC 0-t does not by itself describe the shape of the concentration-time curve or establish a clinical effect. Other pharmacokinetic outcomes may address different aspects of exposure, but the registry record does not provide their results in the posted outcome details.

The endpoint population is participants who completed the study. The record does not report how missing concentration measurements were handled, how the last quantifiable concentration was determined, or whether any participants were excluded from the primary analysis after completion. Those details matter because the endpoint depends on serial blood collection and quantifiable measurements across the assessment interval.

7. Results Posted in the Registry

• Test Product: mean 229.87 versus 220.85 on control; difference 9.02 (95% CI -40.99 to 59.03), standardized effect d = 0.08; z-test p = 0.724.

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a randomized crossover comparison of two formulations. In a crossover study, a participant receives each treatment in separate periods. Because the same person contributes results under both treatments, the analysis can account for stable differences between participants. This can make the within-participant contrast more informative than a comparison that ignores pairing. General statistical principle: the benefit depends on an analysis that correctly represents the pairing, period, and sequence structure.

What does the endpoint summary describe?

AUC 0-t is continuous, so the registry reports a mean and standard deviation for each formulation. The mean describes the average measured exposure in the posted group summary. The standard deviation describes how dispersed individual measurements are around that mean; it is not the uncertainty in the mean itself. The registry lists 229.9 with standard deviation 119.9 for the test formulation and 220.8 with standard deviation 98.6 for the reference formulation. These are marginal summaries and do not show the within-participant relationship between the two measurements.

The sponsor analysis is reported as a ratio of test formulation to reference formulation, with a 90% confidence interval. A ratio is a relative comparison, whereas a mean difference is an absolute comparison in the endpoint's units. General statistical principle: ratios are often useful for pharmacokinetic comparisons when proportional differences are of interest. The registry does not report the analysis method, any transformation, or the criterion used to interpret the interval, so those aspects cannot be reconstructed from the posted result.

What does the re-calculation add?

The unadjusted re-calculation uses the posted means and variability summaries to describe an absolute mean difference. It gives an estimate of 9.02, a 95% confidence interval from -40.99 to 59.03, and an unadjusted p-value of 0.724. This is a simple comparison of posted summaries, not the sponsor's crossover analysis. It does not incorporate the paired measurements or a covariance between the test and reference observations from the same participant. General statistical principle: in a crossover trial, ignoring pairing can change the estimated uncertainty, because the two measurements from each person may be correlated.

The p-value describes how compatible the observed summary difference is with a specified null hypothesis under the assumptions of the calculation. It is not the probability that the null hypothesis is true, and it does not quantify the probability that one formulation is equivalent to the other. Here it is an unadjusted result for a re-calculated difference; the registry does not post a p-value for the ratio analysis. A p-value alone cannot establish practical equivalence, which requires a prespecified margin and a suitable interval-based decision rule.

Why do confidence intervals matter?

A confidence interval conveys the range of estimates compatible with the data and the analysis at the stated confidence level. For the re-calculated difference, the interval is expressed in the original AUC units. For the sponsor's result, the interval is expressed for the test-to-reference ratio. The intervals cannot be compared as if they were on the same scale. General statistical principle: a wider interval indicates less precision, while the substantive meaning of its endpoints depends on the estimand and decision limits relevant to the research question.

The registry does not describe an equivalence margin, a noninferiority margin, or a formal testing procedure, even though the reported analysis is categorized as noninferiority or equivalence. It also does not state whether confidence intervals were adjusted for multiple testing. Therefore, a reader cannot verify the analysis assumptions or reproduce the sponsor's conclusion from the record alone. The reported ratio and interval remain useful descriptive results, but an equivalence decision cannot be independently checked without those missing details.

How does variability affect interpretation?

The reported standard deviations are large relative to the means, indicating considerable spread in the individual AUC summaries. General statistical principle: substantial variability can make an estimated comparison less precise, particularly when the number of independent observations is limited. In a crossover setting, however, the precision of a treatment contrast also depends on the correlation between within-participant measurements. Marginal standard deviations alone do not reveal that correlation, so they are not enough to recover the precision of a paired contrast.

Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model expects. A model that understates variability can produce confidence intervals that are too narrow and tests that overstate evidence. The registry does not report a model or diagnostics that would establish whether over-dispersion was assessed in this analysis. Thus, it is appropriate to treat any discussion of over-dispersion as a general methodological consideration, not as a documented feature of this trial.

The record also does not report the original sample-size justification, missing-data procedures, treatment of below-quantification measurements, period effects, sequence effects, or sensitivity analyses. Those omissions limit the extent to which the sponsor analysis can be independently evaluated. They do not alter the numbers that are posted, but they mean that the analytic details behind them cannot be confirmed from the registry record.

10. Confidence Intervals and Precision

The sponsor's posted ratio estimate is 101.89, with a 90% confidence interval from 94.91 to 109.39. The interval communicates uncertainty around the estimated relative exposure. It spans values below and above 100, so the point estimate alone should not be treated as a complete description of what the data allow. Whether the interval is sufficiently narrow for a bioequivalence conclusion depends on the acceptance limits and analysis procedure, which are not reported in the registry record.

The re-calculated mean difference is 9.02 ng per hour per ml, with a 95% confidence interval from -40.99 to 59.03. This interval includes negative and positive differences, consistent with uncertainty about the direction of the absolute contrast. Its endpoints are expressed on the AUC measurement scale, not as relative percentages. The interval is a simple unadjusted re-calculation and does not use the paired structure of the crossover design.

Confidence intervals should be read as ranges of estimates compatible with the data and statistical assumptions, not as ranges containing a fixed proportion of individual participants' results. They also do not state the probability that a particular hypothesis is true. General statistical principle: interval width depends on variability, information in the data, and the method used to estimate uncertainty. In crossover research, the correlation between a participant's measurements can be important for that width.

These two intervals differ in confidence level, scale, estimand, and analytic basis. The 90% interval belongs to the registry's ratio analysis; the 95% interval belongs to the unadjusted difference re-calculation. Their endpoints should not be compared directly, and one should not be substituted for the other. The record does not provide the sponsor's model or the relevant equivalence bounds, which prevents a fuller assessment of the precision required for the intended decision.

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 sample-size figures are planning illustrations based on the observed re-calculated effect, rather than the original trial design. For the non-time-to-event outcome in this study, the figures are participants per arm, not total event counts. The listed scenarios use 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each scenario, the columns give the number of participants per arm for 80% power and the number of participants per arm for 90% power.

In plain terms, the 80% power column describes the planned sample size under which a study would have an 80% chance of detecting the assumed effect if that effect were real and the planning assumptions held. The 90% power column describes the corresponding planning target for a 90% chance. These are prospective planning concepts, not statements about what this completed study achieved. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect is the stated fraction of the observed effect.

As the planning effect gets smaller, more participants are needed to distinguish it from random variation at the same power target. The listed counts rise across the scenarios from 100% to 75% to 50% of the observed effect. These figures are not observed power. The trial's original sample-size assumptions and justification are not reported in the registry record. Also, the illustration uses the simple unadjusted effect rather than modeling the crossover pairing, so it should be read as a general planning exercise, not as a reconstruction of the trial's own design calculation.

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 = 9.020; pooled standard deviation σ = 109.757.
2. n = 2 × (1.96 + 0.842)² × 109.757² / 9.020² = 2,324.3, rounded up to 2,325 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 <- 9.02000000000001                      # observed difference in means
sigma <- 109.756946021653                     # 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(1330303)
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 = 2,325 (80% power), 3,112 (90% power)
 75% of observed effect: n per arm = 4,133 (80% power), 5,532 (90% power)
 50% of observed effect: n per arm = 9,298 (80% power), 12,447 (90% power)
power.t.test: 2325.2 
Simulated power at n = 2,325 per arm: 0.801 (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 reports the sponsor's primary analysis as a test-to-reference ratio of 101.89, with a 90% confidence interval from 94.91 to 109.39. The analysis is categorized as noninferiority or equivalence, but the method, decision limits, and formal interpretation are not reported. The ratio expresses the comparison on a relative scale and is the posted sponsor result for the primary outcome.

The re-calculation from the posted group summaries is different: it estimates an unadjusted mean difference of 9.02, with a 95% confidence interval from -40.99 to 59.03 and an unadjusted p-value of 0.724. It uses the marginal group means and standard deviations rather than the participant-level paired data from the crossover. It therefore is not a reproduction of the sponsor's analysis and does not estimate the same quantity in the same way.

The registry record does not flag a discrepancy between the posted summary information and the sponsor analysis. Still, the result from the simple re-calculation should be regarded as a descriptive check, not as a replacement for the crossover analysis. No conclusion about satisfying equivalence criteria can be independently verified without the sponsor's method and prespecified limits. The sponsor's ratio result and its interval should be kept distinct from the recalculated absolute difference.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but it posts no secondary outcome results in the record summarized for this trial. The primary outcome is AUC 0-t. The record does not explain how the analyses were organized, which outcomes were designated as primary or secondary beyond the posted primary endpoint, or whether any multiplicity adjustment was planned or used. If several outcomes or comparisons are assessed, multiplicity can increase the chance of at least one apparently notable result by chance. General statistical principle: prespecified testing hierarchies or adjustments can help control that risk, but no such procedure is reported.

The analysis population for the primary outcome is described as participants who completed the study. The registry lists enrollment of 37 and reports 37 participants for each formulation summary. Safety sequence groups list 20 participants at risk each. The record does not explain how these counts relate to one another, whether all enrolled participants completed both periods, or how the analysis population was determined. It does not report participant flow, withdrawals, exclusions, or reasons for missing data.

The record also does not state how incomplete blood sampling or unquantifiable concentrations were handled. Such details can matter for AUC because it is derived from concentration measurements over time. The endpoint description gives the trapezoidal method and the interval ending at the last quantifiable concentration, but it does not specify any imputation, censoring, or sensitivity procedures. The handling of missing outcome data is therefore not reported in the registry record.

The registry identifies a crossover design but does not describe the statistical model or say how period and sequence effects were handled. It does not report the washout interval, whether carryover was assessed, or whether any sensitivity analysis was performed. These omissions prevent a reader from checking the assumptions underlying the sponsor's ratio estimate. They also mean that the simple unadjusted re-calculation cannot fill the gap: it uses aggregate summaries and cannot recover participant-level pairing or period-specific information.

Overall, the posted record provides the endpoint definition, group summaries, and one sponsor analysis, but does not provide a complete statistical analysis plan or a full account of missingness and analysis populations. No unreported methods should be inferred from the crossover structure alone.

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 registry lists serious adverse events by treatment sequence. For the sequence receiving test product in Period 1 and reference product in Period 2, 20 participants were listed at risk and zero serious adverse events were recorded. For the sequence receiving reference product in Period 1 and test product in Period 2, 20 participants were listed at risk and zero serious adverse events were recorded. These figures describe the posted serious-event counts within the sequence groups.

The record does not provide serious adverse event terms, and the list of top serious terms is empty. It also does not report death counts in these groups; deaths are not reported in the registry record. The zero serious-event counts should not be taken to mean that no adverse events of any kind occurred. Other adverse events were listed for the two sequence groups, with six and eight affected participants, respectively, as reported in the registry.

The safety figures are presented by sequence, rather than as a complete treatment-specific comparison across both periods. The record does not explain how events were attributed when participants received both formulations, or whether the at-risk counts reflect the full enrolled population. Enrollment is listed as 37, while each safety sequence group lists 20 at risk; the reason for this difference is not reported in the registry record. These entries are descriptive safety information and do not support broader conclusions about risk in other populations or settings.

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

The registry record documents a randomized crossover study of test and reference tamsulosin formulations under fed conditions in healthy male volunteers. The primary pharmacokinetic outcome is AUC 0-t, a measure of plasma exposure from administration to the last quantifiable concentration. The sponsor's reported estimate is a test-to-reference ratio of 101.89, with a 90% confidence interval from 94.91 to 109.39. Those results describe the estimate and its uncertainty for the registry analysis.

The record does not report the equivalence limits or the analysis method for that ratio. Consequently, the posted result cannot independently establish whether a prespecified bioequivalence criterion was met. The unadjusted re-calculation estimates a mean difference of 9.02, with a 95% confidence interval from -40.99 to 59.03 and an unadjusted p-value of 0.724. That is a distinct, aggregate comparison that does not account for the paired crossover measurements. It should not be treated as a substitute for the sponsor's analysis.

Neither analysis directly measures symptom improvement, disease outcomes, or clinical effectiveness. The study was conducted in healthy male volunteers under fed conditions, and results from that setting do not automatically describe other populations or administration conditions. The endpoint concerns pharmacokinetic exposure, not whether a treatment benefits a person with Prostatic Hyperplasia.

The record also leaves important analytic details unreported, including the original sample-size justification, missing-data handling, treatment of period and sequence effects, and the sponsor's decision criteria. The available evidence can be described precisely at the level of the posted estimates, intervals, and event counts, but its interpretation should remain bounded by those omissions. The absence of reported serious adverse events in the listed sequence groups does not establish that no adverse events occurred or characterize safety beyond the recorded groups.

17. Why This Trial Matters Statistically

This trial is statistically instructive because its crossover design and posted summary results invite two different kinds of comparison. The design has participants receive both formulations, which creates paired observations. The sponsor reports a relative ratio, consistent with expressing exposure comparisons on a proportional scale. By contrast, the simple re-calculation uses an absolute difference between the marginal means. These measures answer related but nonidentical questions and should not be conflated.

The distinction highlights why aggregate means and standard deviations cannot reproduce a crossover analysis. Participant-level pairing can affect uncertainty, but the posted marginal summaries do not include the covariance between each participant's measurements. A simple unadjusted calculation may therefore be useful as a transparent descriptive check while remaining an incomplete representation of the trial design.

The record also illustrates the importance of prespecified decision criteria in equivalence research. A ratio estimate and confidence interval are not sufficient by themselves to verify an equivalence conclusion when the acceptance bounds and analysis method are unavailable. Statistical interpretation depends not only on the point estimate, but also on the intended margin, interval procedure, and analysis population.

Finally, the planning illustrations show how a small assumed effect can demand substantially more participants to reach conventional power targets. Those illustrations use a specified set of planning assumptions, but are not the original design justification and are not observed power. The trial's own sample-size rationale is not reported. Reading the estimates, design, and missing analysis details together helps distinguish what the record establishes from what remains uncertain.

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.

Several limitations specific to this record constrain interpretation. The sponsor's ratio analysis is reported without its statistical method, equivalence limits, or explicit decision rule. Although the analysis is categorized as noninferiority or equivalence, the record does not provide enough information to verify a formal conclusion. The endpoint summaries do not recover the within-participant covariance that is relevant in a crossover study, so the unadjusted re-calculation cannot substitute for a paired analysis.

The registry describes randomization and two treatment sequences but does not report the randomization procedure, washout interval, or handling of period, sequence, or possible carryover effects. It also does not report the original sample-size justification, interim analyses, multiplicity procedures, or sensitivity analyses. These details are not available to assess from the record.

The study's enrollment is listed as 37, while each safety sequence group lists 20 at risk. The record does not explain the difference. The primary endpoint population is described as study completers, but participant flow, exclusions, missing measurements, and the treatment of unquantifiable concentrations are not reported. The posted group summaries list 37 for each formulation, but the record does not clarify how those values relate to the crossover sequences or the analysis population.

Generalizability is also limited by the stated population and conditions: healthy male volunteers and fed administration. The record does not establish whether results apply to other populations or conditions. It reports a pharmacokinetic endpoint, not clinical outcomes. Safety reporting is limited to the listed sequence-group counts, without serious-event terms or reported death counts. These are limitations of what the registry record reports, not evidence that unreported procedures or outcomes were absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: SECOTEX® (Tamsulosin Hydrochloride) Bioequivalence Study Brazil - Fed Admin — NCT01330303.
• Registry record last updated 2017-08-01; status last verified 2017-06.
• Results first posted 2011-04-06.
• 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

NCT01330303 is a completed Phase 1 randomized crossover study sponsored by GlaxoSmithKline. It compared a test tamsulosin hydrochloride 0,4 mg prolonged-release capsule with SECOTEX® 0,4 mg under fed conditions in healthy male volunteers. The registry lists enrollment of 37, an open-label design with laboratory blinding, and two treatment sequences across two periods.

The primary outcome was AUC 0-t among participants who completed the study. The registry reports a test-to-reference ratio of 101.89 with a 90% confidence interval from 94.91 to 109.39. An unadjusted re-calculation from group summaries gives a mean difference of 9.02, a 95% confidence interval from -40.99 to 59.03, and an unadjusted p-value of 0.724. These are different analyses and scales.

The record lists zero serious adverse events in each safety sequence group, while other adverse events were recorded. The analysis method, equivalence limits, original sample-size justification, missing-data handling, and several crossover-analysis details are not reported in the registry record.