Pilot Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men (NCT02697188), a non-randomized phase 2 study. The primary outcome is Mean Serum Testosterone Cavg.

2. Clinical Question

The study’s stated objective was to determine the single-day serum pharmacokinetic profile for two oral testosterone ester formulations, one TE and one TU, given once daily or twice daily. The primary outcome is mean serum testosterone Cavg, measured in ng/dL. Concentrations were scheduled at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose.

This is a pharmacokinetic question: it concerns how measured serum concentrations vary over time after administration, rather than a clinical outcome such as symptom change. The registry also lists mean serum dihydrotestosterone Cmax as a secondary outcome. Numerical results for either outcome are not reported in the registry record, so the stated question can be described but the concentration profiles cannot be compared from this record.

3. Trial Design

The registry identifies this as a phase IIa pilot pharmacokinetic study, with a crossover model, non-randomized allocation and no masking. The study is marked completed. Enrollment is listed as 12. The recorded start is 2007-11 and primary completion is 2008-04.

Five dosing periods are described. Period 1 used 400 mg T as TE once daily. Period 2 used 200 mg T as TU once daily. Period 3 used 200 mg T as TU twice daily, divided as 100 mg per dose. Period 4 used 400 mg T as TU twice daily, divided as 200 mg per dose. Period 5 used 800 mg T as TE twice daily, divided as 400 mg per dose. These descriptions identify the regimens assigned to the periods; details about period order beyond the period labels, transitions between periods, and washout procedures are not reported in the registry record.

A crossover design evaluates measurements under more than one regimen within a study framework. In general, this can make within-person comparisons relevant, but interpretation depends on the actual sequence, completion, timing and analysis. The registry record does not report those details. It also explicitly notes that allocation was non-randomized and that the arms are not a like-for-like control comparison. The periods therefore should not be described as randomized treatment groups or as a conventional randomized treatment-versus-control trial.

The study was sponsored by Clarus Therapeutics, Inc. The registry lists Hypogonadism as the condition. It does not report the rationale for the enrollment target, a detailed eligibility profile, or the protocol’s statistical plan.

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.

TE Period 1 - 400 mg QD

TU Period 2 - 200 mg QD

TU Period 3 - 200 mg BID

TU Period 4 - 400 BID

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 Mean Serum Testosterone Cavg, measured over Concentrations at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose.

The primary endpoint is mean serum testosterone Cavg, reported in ng/dL. Cavg refers to an average concentration measure; such a measure characterizes overall serum exposure over a defined measurement interval rather than focusing on a single peak concentration. The registry describes the outcome as a mean and specifies standard deviation as its dispersion measure.

Concentration measurements were scheduled at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose. These time points provide the intended sampling framework for describing concentration over time following administration. The exact calculation used to derive Cavg, including the interval and computational procedure, is not reported in the registry record.

Pharmacokinetic summaries are useful for characterizing the concentration profile associated with a dosing regimen. An average concentration can complement a peak measure: the registry lists mean serum dihydrotestosterone Cmax as a secondary outcome, where Cmax refers to a maximum concentration measure. These outcomes address different aspects of concentration behavior and are not interchangeable. Neither endpoint, by itself, establishes a clinical benefit or harm.

Although the outcome definition and sampling schedule are present, numerical Cavg estimates and standard deviations are not reported in the registry record. Consequently, the magnitude and precision of the primary endpoint cannot be evaluated from the recorded outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous primary outcome, a mean parameter and standard deviation as the dispersion measure. It does not report the statistical analysis used to summarize or compare the observations. The explanations below describe general statistical concepts; they should not be read as a claim that a particular method was used in this study.

What does a mean summarize?

For a continuous measurement such as serum concentration, a mean describes the central level of the observed measurements. It can be useful for comparing concentration summaries across dosing conditions, but it does not show the shape of the observations or whether a few values strongly influence the average. The registry names mean serum testosterone Cavg as the primary measure, but gives no numerical mean estimates.

What does a standard deviation describe?

A standard deviation describes the spread of observations around a mean. A larger spread indicates greater variability in the measured values, while a smaller spread indicates that values are more clustered. It is not the same as a confidence interval: the standard deviation describes variation among observations, whereas a confidence interval describes uncertainty about an estimated quantity. The registry specifies standard deviation as the dispersion measure but does not report its value.

Why does the sampling schedule matter?

Pharmacokinetic measurements are tied to time after dosing. Concentrations at different time points can characterize different portions of a profile, and summaries such as Cavg or Cmax depend on how the measurements and time interval are defined. The record lists the planned concentration times from -0.5 through 34 hours post dose, but it does not state the exact Cavg derivation or give the measured values. Without those details, the profile cannot be reconstructed from the outcome description alone.

What does a crossover model imply for analysis?

In general, a crossover design can generate measurements under multiple conditions within the same participant. An analysis may need to account for the relationship between measurements from the same person, as well as possible period or sequence effects. Treating correlated observations as independent can misrepresent uncertainty. However, the record does not describe participant-level sequences, completion by period, washout procedures or the model used. It is therefore not possible to determine how, or whether, these design features were handled statistically.

The registry identifies allocation as non-randomized and warns that the arms are not a like-for-like control comparison. Randomization is one way to support comparability by allocating treatment conditions through chance; without it, differences in assignment or period structure may complicate interpretation. This general point does not identify a specific source of bias in this study. The information needed to assess such sources is not reported in the registry record.

How should uncertainty and tests be read?

Inferential summaries such as confidence intervals or p-values can help quantify uncertainty or assess compatibility with a specified statistical model and hypothesis. They do not replace attention to the design, the estimand, measurement quality or the size of an effect. No such estimates or tests are reported in the registry record. Because numerical outcome results are absent, there is no basis for explaining a particular estimate’s precision or statistical significance.

What is a planning illustration?

In general, a sample-size calculation estimates the number of participants needed under chosen assumptions about an effect, variability, significance level, power and allocation. It is a planning exercise, not an observed study result and not a measure of the study’s actual power after completion. The registry describes planning assumptions based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It also states that the illustrations are not the trial’s own design. These assumptions should not be taken as the analysis plan for the crossover study. Numeric planning outputs are not reported in the registry record, and no sample-size illustration can establish what the study observed.

For count outcomes such as adverse events, statistical methods may distinguish the number of participants affected from the number of event occurrences. The registry entries report participants affected, not a detailed event-level analysis. General methods for comparing event rates cannot be applied from these counts alone, particularly without an analysis plan and a clearly defined comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: mean serum testosterone Cavg as the primary outcome and mean serum dihydrotestosterone Cmax as a secondary outcome. It does not report a multiplicity adjustment, a hierarchy for interpreting the outcomes, or a statistical plan describing how multiple outcomes or regimen comparisons were handled. When several outcomes or comparisons are examined, the chance of a chance-positive finding can increase; methods such as prespecifying a primary contrast or adjusting inference can address that issue in general. The record does not say whether such methods were used.

Missing-data handling is not reported in the registry record. It does not state whether measurements were missing, how missing measurements were handled, or whether any imputation or sensitivity analysis was conducted. This matters in a crossover pharmacokinetic study because incomplete observations in a period can affect the amount of information available for describing that regimen and for any within-participant comparison. This is a general consideration, not evidence that missing data occurred.

The analysis population is also not reported. The record does not state whether outcome summaries included all enrolled participants, only those with measurements in a given period, or another defined group. It gives enrollment of 12, but that figure alone does not specify who contributed to each outcome estimate.

The registry lists zero analyses and provides no numerical results for either outcome. Consequently, it is not possible to assess how multiplicity, missingness or analysis-population decisions affected the posted findings. Those details are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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 reports serious adverse events and deaths separately for the five listed regimen groups. For each group, the number of participants at risk is 12, the number affected by serious adverse events is 0, and the number of deaths is 0. These are descriptive registry counts for the groups as named, not estimates from a comparative statistical analysis.

The entries for other adverse events list 3 participants affected with testosterone enanthate 400 mg QD, 3 with testosterone undecanoate 200 mg QD, 3 with testosterone undecanoate 100 mg BID, 4 with testosterone undecanoate 200 mg BID, and 2 with testosterone enanthate 400 mg BID. The record does not provide event-level detail or a statistical comparison of these counts.

A count of zero serious events in a group means none were recorded in that group in the registry entry; it does not prove that the underlying risk is zero. Likewise, these group counts do not establish that regimens differ in safety. The crossover model and non-randomized allocation also mean the entries should not be read as results from a randomized, like-for-like safety comparison. The registry does not report additional context about event definitions, follow-up completeness or safety analysis methods.

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

The record establishes that a completed phase IIa pilot study was designed to characterize the single-day serum pharmacokinetic profiles of oral TE and TU formulations in hypogonadal men. It identifies once-daily and twice-daily regimens, gives a primary concentration outcome and lists the scheduled measurement times. It also lists mean serum dihydrotestosterone Cmax as a secondary outcome.

It does not report numerical results for either outcome. Therefore, the record cannot show the size or direction of differences in serum testosterone Cavg or dihydrotestosterone Cmax among the listed regimens. It also cannot show the precision of those estimates, because means, standard deviations and confidence intervals are not reported. The absence of numerical results in this registry record should not be interpreted as evidence that there was no difference.

The study’s design also limits how comparisons should be characterized. Allocation was non-randomized, and the registry explicitly says that the arms are not a like-for-like control comparison. The regimen periods should not be presented as randomized treatment groups. Details needed to assess period sequence, participant completion and the analysis of repeated measurements are not reported.

The safety entries are similarly descriptive. The record lists zero serious adverse events and zero deaths in each group, alongside counts of participants affected by other adverse events. These figures do not establish comparative safety, and they do not replace a full account of event types, timing or analysis.

In general, a pilot pharmacokinetic study can characterize measurements and inform further research questions. That general role does not establish the clinical consequences of a concentration profile. This registry record does not report symptom outcomes or other clinical efficacy results. It therefore supports conclusions about the intended study question and recorded design, but not a claim that a regimen is clinically beneficial, ineffective or safer than another.

13. Why This Trial Matters Statistically

This trial is statistically notable for the combination of a crossover framework and non-randomized allocation. Crossover studies can be informative when measurements under multiple conditions are related within participants. That structure can require analysis methods that account for within-person dependence and for possible period or sequence effects. The registry identifies the crossover model but does not report the analysis approach or the details needed to assess those issues.

The study also illustrates why a named endpoint is not the same as a reported result. The registry carefully identifies mean serum testosterone Cavg, its unit, the dispersion measure and a set of sampling times. Yet without the numerical outcome estimates, readers cannot assess concentration levels, variability or the precision of any regimen comparison. A well-defined measurement framework is important, but it cannot substitute for the observed results.

The non-randomized allocation is an important interpretive feature rather than a minor label. The registry itself cautions against treating the arms as a like-for-like control comparison. This highlights the need to distinguish a descriptive pharmacokinetic profile from a causal estimate of the effect of one regimen relative to another. The record does not provide enough analysis detail to support such a causal interpretation.

Finally, the safety entries show how descriptive counts should be kept in context. Counts of participants affected can summarize what was recorded, but without event detail, comparative analysis and fuller follow-up information they do not establish differences in risk. The statistical importance of this record lies in understanding the design and limits of the evidence it records, not in drawing treatment conclusions unsupported by its reported outcomes.

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 registry record provides limited information for evaluating the study beyond its stated design and outcome definitions. Numerical results for the primary Cavg endpoint and secondary Cmax endpoint are not reported. Standard deviations are specified for the primary outcome, but their values are absent. The record also lacks confidence intervals, p-values and model-based estimates, so neither magnitude nor precision can be assessed.

Although the design is described as crossover, the record does not state the participant-level treatment sequence, period completion, washout procedures or handling of possible period effects. Those details are important for interpreting repeated pharmacokinetic measurements. The allocation is non-randomized, and the registry warns that the arms are not a like-for-like control comparison; this constrains direct comparative interpretation.

Participant characteristics beyond the condition and enrollment are not reported in the primary outcome description. The analysis population, missing-data approach, statistical model and multiplicity strategy are also not reported in the registry record. These omissions prevent readers from assessing whether the planned outcome analyses align with the design or how incomplete data may have affected the estimates.

The safety information is limited to counts of participants at risk and affected, along with serious adverse event and death counts. Detailed event descriptions, timing and comparative analyses are not reported. These limitations mean that the recorded safety counts should be treated as descriptive, not as a complete assessment of comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men — NCT02697188.
• Registry record last updated 2018-11-01; status last verified 2018-10.
• Results first posted 2018-11-01.
• 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

NCT02697188 is a completed phase IIa pilot pharmacokinetic study of oral testosterone ester formulations in hypogonadal men. The registry lists enrollment of 12, a crossover model, non-randomized allocation and no masking. The study evaluated testosterone enanthate and testosterone undecanoate across once-daily and twice-daily periods.

The primary outcome is mean serum testosterone Cavg in ng/dL, with standard deviation specified as the dispersion measure. Concentrations were scheduled at -0.5, 0, 1, 2, 4, 8, 12, 13, 14, 16, 20, 24 and 34 hours post dose. Mean serum dihydrotestosterone Cmax is listed as a secondary outcome.

Numerical outcome results and statistical analyses are not reported in the registry record. The record lists no serious adverse events or deaths in the regimen groups and provides counts for other adverse events. Because allocation was non-randomized and the registry cautions that the arms are not like-for-like controls, the design and safety entries should be interpreted descriptively.