A Study of Tadalafil in Benign Prostatic Hyperplasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tadalafil in Benign Prostatic Hyperplasia (NCT01183650), a registered phase 1 study. The primary outcome is Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710.

2. Clinical Question

3. Trial Design

This was a completed Phase 1, parallel study sponsored by Eli Lilly and Company. It began in 2010-07 and reached primary completion in 2011-04. The registry record lists 24 enrolled participants with benign prostatic hyperplasia. It identifies Japanese and Caucasian participant groups, with 12 participants in each group. The study was not masked. Allocation is not stated in the registry record.

All participants were assigned the listed intervention of tadalafil 5 mg taken orally daily for 10 days. The study’s stated purpose was to investigate tadalafil pharmacokinetics in Japanese and non-Japanese men with benign prostatic hyperplasia, with safety also to be studied. The primary outcome population is described as all enrolled participants.

The record explicitly cautions that this is not a randomized comparison and that the groups are not a like-for-like control comparison. Accordingly, the participant groups should not be interpreted as randomized treatment arms testing tadalafil against a control. The design can describe pharmacokinetic measurements in the groups listed, but the record does not establish that any observed difference between those groups would be attributable to group characteristics alone or to tadalafil.

The registry record lists three outcome measures and 12 analyses. It does not report a sample-size justification, allocation procedure, detailed analysis plan, or the numerical AUC results. Those omissions constrain interpretation: the design and stated measurement schedule can be described, but the strength and precision of the primary outcome findings cannot be evaluated from the reported information.

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

Analysis population for the primary outcome, as defined in the registry: All enrolled participants

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 Pharmacokinetics: Area Under the Concentration Curve (AUC) for Tadalafil and Metabolite IC710, measured over 1 day and 10 days.

The primary endpoint measures area under the concentration curve, or AUC, for tadalafil and metabolite IC710. AUC represents drug exposure across a specified time interval, incorporating the concentration measurements collected over that interval rather than relying on a single concentration reading. As a general pharmacokinetic concept, it is used to characterize the amount of circulating drug exposure over time.

The registry record specifies AUC(tau [t], day 1) as the area from time zero to 24 hours after dosing on Day 1. For Day 10, it specifies AUC(t,steady state [ss]) as the area during one 24-hour dosing interval at steady state. These are distinct measurement occasions and definitions; they should not be treated as interchangeable without considering their timing.

The reported parameter is the geometric mean, with geometric coefficient of variation as the measure of dispersion. In general, geometric summaries are useful for measurements that are positive and may vary multiplicatively. The coefficient of variation describes relative variability, rather than the absolute spread in the endpoint’s units. No numerical geometric means or dispersion estimates are reported in the registry record, so the endpoint’s observed values and precision are unavailable for interpretation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does AUC represent?

Area under the concentration curve is a summary of concentration over a defined period. As a general statistical and pharmacokinetic explanation, it combines information across the sampling interval, so its value depends on both the concentration pattern and the interval being summarized. AUC is therefore meaningful only when the measurement window is clear. The registry record defines the Day 1 measure as AUC from time zero to 24 hours after dosing and the Day 10 measure as AUC during one 24-hour dosing interval at steady state.

The two timepoints answer related but distinct descriptive questions. Day 1 characterizes exposure over the interval following the initial dose described in the endpoint definition. Day 10 characterizes exposure over a dosing interval at steady state, according to the registry definition. A direct contrast between these measurements would require attention to their timing, the analysis method, and the numerical results. Those details and findings are not reported in the registry record.

Why use a geometric mean?

The primary endpoint is summarized using a geometric mean. As a general explanation, a geometric mean is calculated on a logarithmic scale and then expressed back on the original scale. It can be suitable for positive measurements whose variation is more naturally understood in multiplicative terms. This is different from an arithmetic mean, which summarizes values on their original additive scale. The registry record does not provide an explanation for selecting the geometric mean or describe any transformation used in the analysis.

The corresponding dispersion measure is the geometric coefficient of variation. In general, this expresses variability relative to the scale of the geometric mean, rather than as an absolute distance in ng*hr/mL. It can help characterize how variable exposure measurements are within a group. It does not, by itself, provide a confidence interval for the mean or quantify uncertainty in a contrast. No geometric coefficient of variation values are reported in the registry record.

What can a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the method used to estimate it. Its width conveys precision: wider intervals indicate less precise estimation, while narrower intervals indicate greater precision under the same inferential framework. An interval for an individual group mean and an interval for a difference or ratio between groups address different questions. The registry record does not report confidence intervals for the primary endpoint, so its precision cannot be assessed using that information.

A p-value, if reported, would address how compatible the observed data are with a specified null model, subject to the analysis assumptions. It would not give the probability that a hypothesis is true, nor would it describe the size or practical importance of an effect. The registry record does not report a p-value for the primary endpoint. No test or inferential result should be inferred from the fact that 12 analyses are listed.

Why does the design matter for group comparisons?

A randomized comparison aims to make groups comparable, on average, with respect to factors other than the assigned intervention. This study’s record states that it is not a randomized comparison and that the groups are not a like-for-like control comparison. Both listed groups received tadalafil, and allocation is not stated. Thus, the groups are not a treatment group and a control group. A contrast between Japanese and Caucasian participants, if calculated, would be a descriptive group comparison rather than a randomized estimate of treatment effect.

Parallel describes the study model in the registry record: the listed groups are not described as participants crossing through different treatment conditions. The record does not provide details of participant assignment beyond identifying the groups, and it does not describe adjustment for differences between groups. Any statistical interpretation should therefore avoid attributing group contrasts to a single cause.

What does the analysis population mean?

The primary outcome population is described as all enrolled participants. This identifies the intended population for that outcome in the registry record, but does not establish whether every enrolled participant contributed usable concentration measurements at each timepoint. The record does not report missing-measurement counts, exclusions, deviations from the analysis population, or how incomplete concentration profiles were handled. Without those details, the extent to which the intended population and the analyzed observations coincide is not known.

How should multiple analyses be considered?

The record lists 12 analyses and three outcome measures. In general, when several outcomes or analyses are examined, the chance of obtaining at least one apparently unusual result can depend on the number and relationship of the analyses. Multiplicity methods may be used to control a specified error rate or to organize confirmatory and exploratory questions. The registry record does not report whether multiplicity adjustments were used, which analyses were primary or secondary beyond the stated primary endpoint, or whether the analysis set was prespecified. The number of analyses alone does not show that a multiplicity adjustment was required or omitted.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and 12 analyses, while identifying AUC for tadalafil and metabolite IC710 on Day 1 and Day 10 as the primary endpoint. It does not explain how the analyses map to the outcome measures, distinguish confirmatory from exploratory analyses, or state whether a multiplicity procedure was used. In general, multiplicity matters when several statistical questions are considered because repeated testing can affect the interpretation of nominal evidence. The record does not provide enough detail to determine whether or how that issue was addressed.

The primary outcome population is listed as all enrolled participants. This is an analysis-population description, not a report that all participants had complete endpoint data. The registry record does not report missing AUC measurements, participant exclusions, withdrawals, protocol deviations, or the number of observations contributing to each endpoint summary. It also does not describe imputation, handling of incomplete concentration-time profiles, or sensitivity analyses for missing data.

The statistical analysis plan, including prespecification of models and any adjustment for group characteristics, is not reported in the registry record. The primary endpoint’s numerical estimates and inferential results are also not reported. Consequently, readers cannot determine how missingness, multiple analyses, or analysis choices affected the reported findings. These are limits on what can be evaluated from the registry record, not evidence that any particular method was or was not used.

11. 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.

Most frequent non-serious adverse event terms

The serious adverse-event entries list 0 affected participants among 12 Japanese participants and 0 among 12 Caucasian participants. For other adverse events, the entries list 0 affected participants among 12 Japanese participants and 12 among 12 Caucasian participants. These counts describe the registry’s reported categories; they do not provide event-level detail, severity gradations within the other category, or an attribution assessment.

The groups were not a randomized control comparison, and all listed participants received tadalafil. The counts therefore should be read descriptively, not as a controlled comparison of safety between treatments. The record does not report the number of distinct events, their timing, duration, or relationship to treatment. Death counts are not reported in the registry record. The listed counts also do not establish how completely adverse events were collected or whether any participants had missing safety follow-up.

Because the study enrolled 24 participants in total, these entries are limited descriptions of the observed safety record, not precise estimates of event frequency in a broader population. No conclusion about safety beyond the recorded counts can be drawn from these entries alone.

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

The registry record describes a Phase 1 study of tadalafil pharmacokinetics in men with benign prostatic hyperplasia. Participants received tadalafil 5 mg orally daily for 10 days, and the primary endpoint concerned AUC for tadalafil and metabolite IC710 on Day 1 and Day 10. The reported measurement definitions identify the time intervals and the intended geometric summaries.

However, the registry record does not report numerical AUC estimates, geometric coefficients of variation, confidence intervals, or a primary statistical comparison. This means the size and precision of the pharmacokinetic findings cannot be assessed. Missing numerical findings are not the same as a finding of no difference or no effect; the record does not establish either conclusion.

The Japanese and Caucasian participant groups are not described as randomized or as a like-for-like control comparison. They both received tadalafil. Any group contrast would therefore be descriptive in this record and should not be read as a causal treatment comparison. The record also does not report the methods needed to evaluate whether other differences between groups were considered.

The adverse-event entries describe no serious adverse events in either group, with other adverse events reported for 0 of 12 Japanese participants and 12 of 12 Caucasian participants. Event details and death counts are not reported. These safety counts do not provide a randomized estimate of comparative risk and do not resolve the absence of numerical primary endpoint findings.

In general, a study’s measurement plan can clarify what investigators intended to learn, while interpretation of results depends on the estimates, their precision, and the analysis methods. For this study, the endpoint definitions and participant counts are available, but the primary numerical findings and important analysis details are not reported in the registry record. Conclusions should remain within those limits.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a study question and a result that can be quantitatively interpreted. The registry record specifies pharmacokinetic exposure as the primary focus, defines AUC measurement intervals on Day 1 and Day 10, and identifies geometric mean and geometric coefficient of variation as the summary approach. Those details help clarify the intended measurement, but they cannot establish the observed level or variability of exposure without numerical endpoint results.

It also illustrates why design labels matter. The study is parallel and not masked, but it is explicitly not a randomized comparison. The Japanese and Caucasian groups both received tadalafil, and the registry record cautions that they are not a like-for-like control comparison. A statistical contrast between groups, even if available, would not have the interpretation of a randomized treatment-versus-control effect.

The record also raises practical questions for statistical reporting. It lists 12 analyses and three outcome measures, but does not describe multiplicity handling, missing-data methods, or the detailed analysis plan. Such information helps readers understand whether estimates were prespecified, how incomplete data were treated, and how findings across multiple analyses should be interpreted. Its absence limits evaluation without establishing that any particular method was inappropriate.

Finally, the safety entries are counts that should be interpreted in context. They are descriptive observations from 24 enrolled participants, not precise comparative safety estimates. Taken together, the record shows how a defined endpoint and a completed study can still leave important questions unanswered when numerical findings and analysis details are not reported.

14. 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 main limitation for interpreting the primary outcome is that numerical AUC results are not reported in the registry record. Geometric means, geometric coefficients of variation, confidence intervals, and statistical tests are unavailable. Consequently, readers cannot assess the magnitude, variability, or precision of tadalafil or metabolite IC710 exposure at either measurement occasion.

The study is not a randomized comparison, and the record explicitly cautions that the groups are not a like-for-like control comparison. Both groups received tadalafil, and allocation is not stated. A comparison of Japanese and Caucasian participants therefore cannot be treated as an estimate of tadalafil versus control, and the record does not describe adjustment for group differences.

The enrolled sample was 24 participants, with 12 in each listed group. This limits how much detail the study can provide about variability and uncommon safety outcomes. The registry record does not report a sample-size justification or explain whether the enrollment was intended to support a specific level of precision for the pharmacokinetic endpoints.

Important analysis details are also not reported: the statistical analysis plan, handling of missing data, participant exclusions, multiplicity procedures, and the mapping of 12 analyses to three outcome measures. The primary endpoint population is stated as all enrolled participants, but the record does not establish how many contributed usable measurements at each timepoint. Safety reporting lacks event-level descriptions and does not report death counts. These omissions narrow the conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Tadalafil in Benign Prostatic Hyperplasia — NCT01183650.
• Registry record last updated 2012-05-16; status last verified 2012-04.
• Results first posted 2012-05-16.
• 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.

18. Record Summary

This completed Phase 1 parallel study evaluated tadalafil pharmacokinetics in Japanese and non-Japanese men with benign prostatic hyperplasia. It enrolled 24 participants: the registry lists 12 Japanese participants and 12 Caucasian participants. The intervention was tadalafil 5 mg orally daily for 10 days. The study was not masked, and allocation is not stated.

The primary endpoint was AUC for tadalafil and metabolite IC710 on Day 1 and Day 10, summarized using geometric means and geometric coefficients of variation. The primary outcome population was all enrolled participants. Numerical AUC findings are not reported in the registry record.

Serious adverse events were reported for 0 of 12 Japanese participants and 0 of 12 Caucasian participants. Other adverse events were reported for 0 of 12 Japanese participants and 12 of 12 Caucasian participants. Event details and death counts are not reported. The record also does not describe the detailed statistical plan, missing-data handling, or multiplicity procedures.