Tamsulosin Hydrochloride 0.4 mg Capsules Under Fed Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tamsulosin Hydrochloride 0.4 mg Capsules Under Fed Conditions (NCT01149733), a randomized phase 1 study. The primary outcome is Cmax (Maximum Observed Concentration of Drug Substance in Plasma).

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, unmasked crossover study of two tamsulosin hydrochloride 0.4 mg capsule formulations under fed conditions. Its stated objective was to evaluate comparative bioavailability after a single dose in healthy subjects. The study was sponsored by Teva Pharmaceuticals USA and is recorded as completed. The recorded start and primary completion are both 2004-11.

The crossover model means that the comparison concerns formulations evaluated within a crossover design, rather than a conventional parallel-group trial in which each participant is assigned to only one formulation. Randomization is reported, but the registry record does not describe the sequence allocation, treatment periods, washout, or the timing of administration beyond the single-dose and fed-condition description. It also does not explain how the crossover structure was incorporated into the sponsor's analysis.

The primary endpoint records give 16 observations for Tamsulosin and 16 for Flomax®. Those entries are endpoint-specific group counts; they should not be treated as evidence that the study was analyzed as a parallel trial. The safety record instead lists 32 participants at risk for each formulation. The registry record does not explain the difference between the endpoint counts and the safety denominators, identify exclusions, or report completion by period.

Masking is recorded as none. This describes the reported masking status, but the registry record does not explain whether endpoint measurement or laboratory procedures were performed without knowledge of formulation. The record lists three outcome measures and three analyses, but no secondary outcomes are posted. Detailed information about recruitment, eligibility criteria beyond healthy status, analysis populations, and the trial's original statistical plan is 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.

Overall 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 Cmax (Maximum Observed Concentration of Drug Substance in Plasma), measured over Blood samples drawn over 60 hour period.

The primary endpoint was Cmax, the maximum observed concentration of drug substance in plasma. It is a continuous measure reported in ng/mL, summarized in the registry using means and standard deviations. Blood samples were drawn over a 60 hour period, and the endpoint description states that bioequivalence was based on Cmax.

As a general statistical concept, Cmax captures the observed peak concentration within the sampling period. It can help characterize the concentration profile following a dose, while other measures may describe different aspects of exposure. The endpoint is useful for a formulation comparison because the two products can be assessed using the same measured quantity under the study's stated fed condition. However, Cmax alone does not describe every feature of a concentration-time profile.

The reported means were 8.869 ng/mL for Tamsulosin and 9.015 ng/mL for Flomax®. The registry also reports a sponsor analysis using the ratio of geometric means, a distinct summary from the unadjusted arithmetic mean comparison. The record does not give the complete endpoint sampling schedule, details of the laboratory assay, or a stated rule for handling missing samples. It also does not report equivalence limits for the Cmax analysis. Those omissions limit how fully the endpoint result can be reconstructed from the registry record.

7. Results Posted in the Registry

• Flomax®: mean 9.02 versus 8.87 on control; difference 0.15 (95% CI -18.58 to 18.87), standardized effect d = 0.01; z-test p = 0.988.

8. Statistical Interpretation

9. Statistical Methods Explained

The record contains an unadjusted recalculation from posted summary statistics and a sponsor-reported ratio of geometric means. These address the formulation comparison using different summaries and scales. Understanding that distinction helps avoid treating the estimates as interchangeable.

What does the unadjusted mean difference describe?

A mean difference subtracts one group's arithmetic mean from the other group's arithmetic mean. The posted means are 8.869 ng/mL for Tamsulosin and 9.015 ng/mL for Flomax®, and the recalculated mean difference is 0.146. The reported confidence interval runs from -18.58 to 18.87, and the unadjusted p-value is 0.988. These are the recalculation's reported results; no further calculation is needed to interpret their direction or uncertainty.

In general, an unadjusted comparison does not account for covariates or design features unless they are included in the calculation. This study is identified as a crossover, but the recalculation is described as an unadjusted re-calculation from posted summary statistics. The record does not report whether the summary-statistic calculation incorporates the paired structure. Its result should not be assumed to represent a period-adjusted or participant-paired treatment estimate.

Why is the sponsor's ratio on a different scale?

The sponsor-reported statistic is a ratio of geometric means, with a value of 97.90 and a 90% confidence interval from 91.00 to 105.32. A geometric mean is commonly used for positive measurements that are analyzed on a logarithmic scale, with results then expressed as a ratio. As a general explanation, a ratio near the reference value indicates that the geometric means are close on that ratio scale. The registry record does not provide enough method detail to confirm the exact transformation, model, or back-transformation used in the sponsor analysis.

The sponsor result is not a second expression of the arithmetic mean difference. The two analyses differ in their reported summary measure and confidence interval. The record does not give the sponsor's p-value, model specification, or equivalence limits. As a result, the geometric-mean ratio can be described as posted, but the record does not allow a full reconstruction of the sponsor's inferential procedure.

What do standard deviations and uncertainty mean?

The registry reports standard deviations of 28.0 for Tamsulosin and 26.0 for Flomax®. A standard deviation describes spread among observations around a mean; it is not the same quantity as a confidence interval or a standard error. The comparison record also reports a pooled standard deviation of 27.02, along with standard errors of 7.0 and 6.5 for the two arms. These are posted summary statistics, and the page should not be read as if the standard deviations were the uncertainty bounds for the means.

As a general concept, a confidence interval conveys uncertainty about an estimated quantity under a specified statistical method. Its width depends on the variability in the data, the amount of information available, and the analysis design. A p-value addresses compatibility of the data with a stated null hypothesis under a test; it does not quantify the probability that the null is true, nor does it establish equivalence.

Why does the crossover structure matter?

In a crossover trial, participants can contribute observations under more than one treatment condition. When measurements from the same person are related, a paired analysis can use that within-person relationship to estimate a treatment contrast. General statistical methods for crossover data may also consider period and sequence effects, depending on the design and analysis plan. The registry identifies this study as crossover but does not describe its periods, sequences, washout, or the model used by the sponsor.

The summary records list 16 endpoint observations under each formulation, while safety records list 32 participants at risk for each. The record does not explain the analysis-set definitions or why the endpoint counts differ from the safety denominators. These numbers should be read in their respective contexts rather than combined or interpreted as a participant flow.

What does the reported p-value establish?

The unadjusted p-value is 0.988. As a general explanation, a p-value is calculated under a null hypothesis and the assumptions of a specified test. A large p-value means that the data do not provide a basis for rejecting that null under that test; it does not prove that the null is correct. Equivalence requires a prespecified margin and an analysis that evaluates whether the uncertainty lies within that margin. The registry record does not report the margins or the method behind the sponsor's analysis, so the p-value must not be treated as an equivalence conclusion.

There is no reported discrepancy between the sponsor analysis and the recalculation. Even so, they have different scales and reported confidence levels, and the sponsor result is the study's own posted analysis. The recalculation is a supplementary, unadjusted summary-statistic comparison. The registry record does not identify the statistical method behind the sponsor result, so the two results should be kept distinct rather than reconciled by assumption.

10. Confidence Intervals and Precision

The unadjusted mean-difference estimate is 0.146, and its confidence interval extends from -18.58 to 18.87. The interval includes zero and spans values on both sides of the point estimate. As a general statistical interpretation, this indicates that the unadjusted data are compatible with a range of possible mean differences under the calculation's assumptions. The interval is broad, so the point estimate alone gives an incomplete picture of uncertainty.

The sponsor's ratio of geometric means is 97.90, with a 90% confidence interval from 91.00 to 105.32. This interval is on the ratio scale and should not be confused with the unadjusted mean-difference interval. The registry labels the sponsor analysis as a non-inferiority-or-equivalence legacy type, but the record does not report the acceptance limits. Without those limits, the interval cannot be judged against a registry-stated equivalence criterion.

Confidence intervals express uncertainty around an estimate under a method and its assumptions; they are not ranges containing a fixed proportion of individual observations. A narrower interval generally indicates greater precision for the estimated quantity, while a wider interval indicates less precision. In general, the precision of a crossover comparison can depend on within-participant variability and the correlation between measurements. Those details are not reported in the registry record.

The endpoint standard deviations are 28.0 and 26.0, and the recalculation reports a pooled standard deviation of 27.02. The record does not provide the participant-level observations needed to independently assess distribution shape, outliers, or the paired covariance. The displayed intervals therefore provide the available uncertainty summaries, but the registry record does not permit a full check of the assumptions behind either analysis.

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 event counts. They use the observed effect as a starting point and illustrate planning at 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The original trial's own design assumptions are not reported in the registry record.

For 100% of the observed effect, the illustration gives 540,553 participants per arm for 80% power and 723,647 participants per arm for 90% power. For 75% of the observed effect, it gives 960,983 participants per arm for 80% power and 1,286,483 participants per arm for 90% power. For 50% of the observed effect, it gives 2,162,210 participants per arm for 80% power and 2,894,586 participants per arm for 90% power.

In plain terms, the 80% power column describes an illustrative sample size intended to give an 80% chance of detecting the stated effect under the planning assumptions if that effect were real. The 90% power column uses a higher target chance of detection under those same assumptions. Smaller effects require more participants to detect with a given power and significance level, which is why the illustrative counts rise as the assumed fraction of the observed effect falls.

These figures are planning illustrations based on the observed effect, not observed power and not evidence about the study's original planning. They are not a recommendation for a future study. The crossover design and the lack of reported original design assumptions also mean that these simple equal-allocation illustrations should not be taken as a reconstruction of the trial's 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 = 0.146; pooled standard deviation σ = 27.019.
2. n = 2 × (1.96 + 0.842)² × 27.019² / 0.146² = 540,552.4, rounded up to 540,553 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 <- 0.1456                      # observed difference in means
sigma <- 27.0185121722126                     # 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(1149733)
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 = 540,553 (80% power), 723,647 (90% power)
 75% of observed effect: n per arm = 960,983 (80% power), 1,286,483 (90% power)
 50% of observed effect: n per arm = 2,162,210 (80% power), 2,894,586 (90% power)
power.t.test: 540553.3 
Simulated power at n = 540,553 per arm: 0.802 (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 sponsor-reported analysis gives a ratio of geometric means of 97.90, with a 90% confidence interval from 91.00 to 105.32. It is recorded as a non-inferiority-or-equivalence legacy analysis. The registry record does not state its method, decision limits, or p-value, so its result can be described but not independently assessed against a complete decision rule.

The unadjusted recalculation instead compares the posted arithmetic means. It reports a mean difference of 0.146, a confidence interval from -18.58 to 18.87, and an unadjusted p-value of 0.988. These are not the same estimand: a geometric-mean ratio and an arithmetic mean difference are expressed on different scales and may reflect different analysis procedures.

The record reports no discrepancy between the analyses. The sponsor result remains the study's own posted analysis, while the recalculation is an unadjusted re-analysis from summary statistics. The registry does not report enough detail about the crossover model, participant pairing, or the sponsor's statistical method to establish that the recalculation reproduces the sponsor analysis. Neither result should be interpreted using an equivalence margin that is not stated in the registry record.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but no secondary outcomes are posted. The primary endpoint is identified as Cmax, and one sponsor-reported ratio of geometric means is recorded. The registry record does not provide a full analysis plan that would show which endpoints or contrasts were considered confirmatory, how outcome families were defined, or whether any adjustment for multiple testing was planned.

As a general statistical concept, multiplicity arises when several hypotheses or outcomes are tested. Considering more tests can increase the chance of at least one apparently notable result under a collection of null hypotheses. Methods to address multiplicity depend on the analysis objectives and prespecified plan. Since that plan is not reported in the registry record, it is not possible to determine whether multiplicity procedures were intended or used.

The record does not describe missing-data handling, the number of participants contributing to each period, exclusions from the primary analysis, or the definition of the analysis population. It also does not report participant flow or reasons for any missing endpoint measurements. The endpoint arm entries list 16 observations for each formulation, while the adverse-event entries list 32 participants at risk for each; the registry does not explain the analysis-set distinction.

For a crossover study, details such as treatment sequence, period, and within-participant pairing can be important to the analysis. Those details, along with any rules for handling incomplete crossover data, are not reported in the registry record. The study's original statistical plan, any interim analyses, and sample-size justification are also not reported in the registry record. No conclusions about their presence or absence should be inferred from the posted outcome summaries alone.

The sponsor's analysis method is not named, and the record does not report an analysis population or missing-data approach for that result. The unadjusted re-calculation does not supply those missing design and analysis details. Accordingly, the registry provides numerical results but not enough documentation to assess all assumptions, analysis choices, or the treatment of incomplete observations.

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 5% reporting threshold.

The adverse-event record lists zero serious adverse events among 32 participants at risk for Tamsulosin and zero among 32 participants at risk for Flomax®. It also lists zero other adverse events among 32 participants at risk for each formulation. These are the posted counts for the recorded risk groups.

The safety denominators are distinct from the endpoint arm counts, which list 16 observations for each formulation. The registry record does not explain the difference in denominators, and the safety figures should be read as recorded rather than combined or interpreted as a participant-flow account. The crossover design also means that the formulation-specific risk entries should not be assumed to represent non-overlapping groups.

Zero recorded events in these entries means that no events were reported in the registry's stated categories for those at-risk groups. It does not establish that no event could occur, and it does not by itself provide a precise estimate of uncommon risks. The record does not list serious adverse-event terms, and deaths are not reported in the posted safety information. These safety summaries describe what was recorded in this trial; they do not support broader conclusions about safety.

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

The posted Cmax results show similar observed arithmetic means for the two formulations: 8.869 ng/mL for Tamsulosin and 9.015 ng/mL for Flomax®. The unadjusted recalculation reports a mean difference of 0.146, a confidence interval from -18.58 to 18.87, and an unadjusted p-value of 0.988. The sponsor's result is a ratio of geometric means of 97.90, with a 90% confidence interval from 91.00 to 105.32. Each statistic describes the comparison on its own scale.

The results do not, by themselves, establish that the formulations are equivalent. Equivalence is assessed against prespecified limits using an appropriate analysis; those limits and the sponsor's detailed method are not reported in the registry record. A non-significant unadjusted comparison does not prove equality, and a point estimate close to a reference value does not show how precisely the difference has been estimated. The confidence intervals convey uncertainty, but their interpretation depends on the estimand and method.

The study was a randomized, unmasked, single-dose crossover comparison conducted under fed conditions in healthy subjects. It therefore addresses a specific formulation comparison and measured endpoint in the stated study setting. The registry record does not describe enough about the treatment sequence, periods, missing observations, analysis population, or crossover model to reconstruct the full inferential analysis. The posted endpoint summaries also do not describe every aspect of drug exposure.

The safety entries report zero serious and zero other adverse events for each formulation among the stated at-risk groups. Those observations are limited to the trial's posted safety reporting and do not establish the absence of risk beyond the study. More broadly, the numerical results should be treated as trial findings in the registry record, not as medical advice or as a conclusion about outcomes that the study did not measure.

17. Why This Trial Matters Statistically

This study offers a useful statistical example because it brings together a crossover design, a continuous concentration endpoint, and more than one way of expressing a formulation contrast. The unadjusted arithmetic mean difference and the sponsor's geometric-mean ratio answer related but non-identical questions. Keeping their scales distinct is essential to accurate interpretation.

The contrast between a point estimate and its uncertainty is also instructive. The observed means are close, while the unadjusted confidence interval extends from -18.58 to 18.87. A point estimate alone can make a comparison look more decisive than its precision supports. Confidence intervals help show how much uncertainty remains under the analysis used.

The crossover designation matters statistically because measurements from the same participant may be related. A fully specified analysis can use that structure, but the registry record does not describe the sponsor's model or the within-participant information. That gap illustrates why summary statistics do not always allow a reader to reproduce a trial's primary analysis, even when the main estimates are posted.

Finally, this record illustrates the difference between a result that is compatible with little observed difference and a formal demonstration of equivalence. Equivalence depends on explicit margins and a specified method, neither of which is reported in detail. Recognizing what the record establishes—and what it leaves undocumented—is a central part of statistical reading.

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 record leaves important trial-specific details unreported. It identifies the study as a randomized crossover trial but does not give the treatment sequences, period structure, washout, or the statistical model used for the sponsor's analysis. These details matter when interpreting a crossover comparison because the analysis may need to account for repeated measurements and period-related structure.

The record does not state the equivalence limits for the Cmax analysis. Although a sponsor-reported ratio of geometric means and 90% confidence interval are posted, the decision rule and analysis method are not. The result therefore cannot be independently classified against a registry-stated equivalence criterion.

The endpoint counts are 16 observations for each formulation, while safety denominators are 32 for each formulation. The registry does not explain the difference or provide participant flow, completion by period, exclusions, or reasons for missing endpoint observations. It also does not identify the primary analysis population or describe missing-data handling.

The study evaluated a single dose under fed conditions in healthy subjects. This specific setting limits what can be inferred about other populations, dosing conditions, or outcomes not measured in the study. The endpoint is Cmax, and the registry does not provide the complete concentration-time data needed to assess other features of exposure.

The original sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record. The posted planning illustrations are based on the observed effect and do not recover the study's original design rationale. The record also lists no secondary outcomes as posted, limiting the range of outcomes available for interpretation.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Tamsulosin Hydrochloride 0.4 mg Capsules Under Fed Conditions — NCT01149733.
• Registry record last updated 2024-08-20; status last verified 2024-08.
• Results first posted 2010-09-13.
• 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

NCT01149733 records a completed, phase 1 randomized, unmasked crossover study of two tamsulosin hydrochloride 0.4 mg capsule formulations under fed conditions. The objective was to compare bioavailability after a single dose in healthy subjects. Enrollment was 32, and the recorded start and primary completion are both 2004-11.

The primary outcome was Cmax, measured in ng/mL, with blood samples drawn over a 60 hour period. The unadjusted recalculation reports a mean difference of 0.146, a confidence interval from -18.58 to 18.87, and a p-value of 0.988. The sponsor-reported ratio of geometric means is 97.90, with a 90% confidence interval from 91.00 to 105.32.

The record lists zero serious and zero other adverse events among 32 participants at risk for each formulation. Detailed crossover methods, equivalence limits, analysis populations, missing-data procedures, and the original statistical plan are not reported in the registry record.