Dosing Validation Study of Oral Testosterone Undecanoate (TU, LPCN 1021).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dosing Validation Study of Oral Testosterone Undecanoate (TU, LPCN 1021). (NCT03242590), a na phase 3 study. The primary outcome is Percent of LPCN 1021-treated Subjects Who Achieve a Total Testosterone Average Concentration [Cavg] in the Normal Range.

2. Clinical Question

In statistical terms, the stated question is about the frequency of a binary outcome within the treated group: whether each participant’s average concentration was inside or outside the specified range. It is not a question about how much concentrations changed from baseline, nor a comparison of outcomes between randomized groups. Without a reported endpoint estimate, the record does not establish how many participants met the criterion or how precisely that proportion was estimated.

3. Trial Design

This was a Phase 3, multicenter, open-label, single-group study of oral testosterone undecanoate LPCN 1021. The registry record lists the study as completed, with a start in 2016-12 and primary completion in 2017-03. It records 95 participants enrolled and describes the study population as adult hypogonadal male subjects. The listed condition is male hypogonadism.

The intervention was LPCN 1021, described as oral testosterone undecanoate at 225 mg TU two times a day. The study description identifies one treatment and no control group. Allocation is recorded as NA, and the design is listed as single group. Thus, the planned comparison is not between randomized arms; the primary endpoint concerns the proportion meeting a concentration criterion within the treated group.

Open-label means the study was not masked, as also indicated by the masking entry of NONE. The registry record does not report a blinded assessment procedure. With no concurrent comparator identified, changes or outcomes cannot be separated from other influences by a between-group comparison. This design can describe the observed outcome in the treated study population, but does not produce a randomized estimate of the difference attributable to treatment.

The primary endpoint was assessed at Visit 4, described as Day 24 ± 4 days, following 24 days of treatment. Its specified population is the Safety Set. Further details of the set’s inclusion rules are not reported in the registry record. A protocol, sample-size justification, details of any interim analyses, and a fuller statistical analysis plan are also not reported in the registry record. The record’s design and timing establish the basic frame for interpreting the endpoint, but not all operational or analytical details.

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: Safety Set

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 Percent of LPCN 1021-treated Subjects Who Achieve a Total Testosterone Average Concentration [Cavg] in the Normal Range, measured over Following 24 days of treatment.

The primary endpoint is the percentage of LPCN 1021-treated participants whose 24-hour average serum testosterone concentration, or Cavg, was within the stated normal range of 300 to 1080 ng/dL. It was assessed at Visit 4, identified as Day 24 ± 4 days, following 24 days of treatment. The specified analysis population is the Safety Set.

This is a binary outcome at the participant level: a participant either meets the concentration criterion or does not. The endpoint converts those individual classifications into a proportion for the study group. Such an endpoint can express how often a predefined target was achieved at a particular assessment, rather than describing the full distribution of measured concentrations or their change from baseline.

The range supplies the threshold used to classify the outcome. It does not, by itself, describe how far a participant’s concentration was from either boundary, how concentrations varied across participants, or whether values remained in range at other times. The registry record gives the endpoint definition and states that its dispersion measure is a 95% confidence interval. However, it does not report the observed percentage or the interval limits. Consequently, the endpoint’s magnitude and precision cannot be evaluated from the registry result information.

Because the study has a single group and no comparator, the endpoint is descriptive of outcomes among treated participants. It does not estimate a relative effect against an untreated or differently treated group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion, because each participant is classified according to whether the specified average concentration lies within the normal range. For a binary endpoint, the basic descriptive result is the share of participants meeting the criterion among those included in the endpoint analysis. The registry record identifies the Safety Set as the population and a 95% confidence interval as the dispersion measure, but does not report the estimated share, the interval limits, or the denominator used for the primary analysis.

A confidence interval is a statistical range constructed to express uncertainty around an estimate under a specified method. In general, narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. The interval’s interpretation depends on the analysis method and the data used. Because the estimate and interval are not reported in the registry record, their precision cannot be assessed. The confidence level alone is not enough to reconstruct either value.

The design is single group, with allocation listed as NA and masking listed as NONE. As a result, the primary endpoint analysis is not a comparison of two randomized treatment groups. It can summarize the observed outcome in the treated group, but a comparison against a control group is not available. General statistical methods for treatment contrasts require outcome information from the groups being compared; a single-group proportion does not supply that contrast.

The endpoint’s measurement window is also part of its statistical definition. The registry identifies Visit 4 as Day 24 ± 4 days and says the primary endpoint followed 24 days of treatment. A threshold-based endpoint describes classification at this assessment, rather than a continuous pattern over time. The registry record does not state how a concentration value outside the measurement window would be treated or provide additional assessment timing details.

The registry lists the primary efficacy endpoint and identifies the Safety Set, but does not report a fuller statistical analysis plan. Details such as the exact calculation method for the proportion and confidence interval, how missing endpoint values were handled, and whether any covariate adjustment was planned are not reported in the registry record. These details can affect the analysis population, estimate, or uncertainty and should not be inferred from the endpoint title.

The planning assumptions described for the sample-size illustration are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These assumptions are planning conventions for an illustration; they do not establish the design used for this single-group study. In particular, an equal-allocation, two-arm planning scenario is not the same as this registry’s single-group treatment design. Sample-size illustrations are not observed power and do not report trial outcomes.

For binary outcomes, the underlying event frequency can affect the precision of a proportion estimate. General statistical methods may also be affected when observations are more variable than a model assumes; over-dispersion is one name for that situation in relevant models. The registry record does not report use of an over-dispersion model, nor does it provide information that would establish whether such a model was needed. It would not be appropriate to infer a particular model from the endpoint’s binary form alone.

The posted endpoint information does not give enough detail to reproduce the analysis. Recalculated estimates from summary statistics would require reported numerical results and a clear basis for the calculation. The registry record gives neither the primary percentage nor its interval limits. No independent numerical recalculation is therefore described. If recalculated values and an official analysis were ever to differ, the sponsor’s own analysis would take precedence, as stated for recalculated results generally.

Interpretation should distinguish estimation from hypothesis testing. A confidence interval describes uncertainty around an estimated proportion; a significance test addresses a defined null hypothesis under stated assumptions. The registry record reports the interval type but does not report a primary test result, hypothesis, or p-value. It does not report a statistical plan sufficient to establish what test, if any, was used. The absence of these details in the registry record is not evidence that a particular method was or was not used.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Oral Testosterone Undecanoate, LPCN 1021")
n      <- c(95)
events <- c(76)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Oral Testosterone Undecanoate, LPCN 1021  95  76  80.0  70.5  87.5  70.9  86.8  70.8  86.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome measure and reports no analyses. It does not describe a multiplicity strategy, such as adjustment across multiple endpoints or repeated tests. The record therefore does not establish whether multiplicity was considered in the trial’s full analysis plan. It would be inappropriate to infer an adjustment method or to conclude that none was used.

The primary endpoint is assigned to the Safety Set, but the registry record does not report the rules defining that set or give an endpoint-specific denominator. It also does not report how missing concentration measurements, missed visits, or other unavailable endpoint data were handled. No imputation, exclusion, or sensitivity-analysis approach is described in the information reported for this analysis. These choices can affect both the estimated proportion and its precision, so the missing details limit independent assessment.

The record gives no endpoint estimate, confidence interval limits, test result, or p-value. It also does not report a detailed statistical analysis plan, interim-analysis procedures, or sample-size justification. The documented primary endpoint and named analysis population clarify what was intended to be assessed, but do not fill in the missing analytical details. Their absence from the registry record should be read as unavailable information, not as evidence that the corresponding procedures did not occur.

12. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastric ulcer hemorrhage (1.1%).

The registry record lists one serious adverse event affecting one participant in the LPCN 1021 group, with 95 at risk. The top serious adverse event term is Gastric Ulcer Hemorrhage, reported as 1.1%. The record lists six participants with other adverse events and zero deaths. These figures describe the entries reported for the study group; they do not establish that an event was caused by the intervention.

Serious adverse events and other adverse events are distinct categories in the registry presentation. The serious-event count should not be conflated with the count for other adverse events, and the categories should not be combined. The record does not provide further detail about event timing, severity beyond the serious classification, recurrence, relatedness assessment, or the full set of adverse-event terms.

These are descriptive safety figures from a single-group study. Without a comparator, the registry record does not provide a like-for-like basis for estimating whether an event occurred more often than under another condition. The reported counts also do not, by themselves, establish causation. The listed top serious-event term and its reported percentage should be interpreted as registry safety information, with the limitations of the available reporting detail.

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

The study asks whether participants receiving oral testosterone undecanoate LPCN 1021 reached a defined concentration range at a specified assessment. The registry record makes the outcome rule clear: a 24-hour average serum testosterone concentration within 300 to 1080 ng/dL at Visit 4, Day 24 ± 4 days, following 24 days of treatment. It also identifies the Safety Set as the endpoint population and a 95% confidence interval as the intended measure of dispersion.

The registry record does not report the actual percentage meeting that criterion or the interval limits. Thus, it does not establish from the reported information how common the endpoint was or how precisely it was estimated. The endpoint definition cannot substitute for the result. Nor can an enrollment figure or a planning illustration reveal the observed endpoint value.

Even if the proportion were reported, this single-group, open-label study would describe outcomes in the treated group rather than provide a randomized comparison. It would not show the difference between treatment and a control condition, and it would not by itself separate treatment effects from other factors that could influence the measured outcome. The absence of a comparator is central to the scope of inference, not a minor technical detail.

The endpoint also has a specific scope. It classifies an average concentration at one stated assessment against a range. It does not, on its own, describe individual concentration trajectories, the duration of time in range, changes from baseline, or outcomes beyond the assessment window. Those questions would require additional reported measures and analyses.

The safety entries describe adverse-event counts and a reported serious-event term, but do not establish causation or comparative safety. Overall, the record defines what the study intended to measure and offers limited safety counts, while leaving the primary efficacy estimate and important analytical details unreported. The appropriate interpretation is therefore bounded: the design and endpoint can be described, but the primary observed result and its precision cannot be assessed from the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a clearly defined endpoint and a reported endpoint result. The registry record specifies a threshold-based measure, its assessment timing, an analysis population, and a confidence-interval type. Those details describe the intended estimand at a basic level: the proportion of treated participants meeting a concentration criterion at the stated visit. But without the estimate and interval limits, readers cannot assess either its magnitude or precision.

The single-group design also makes the comparison question important. A proportion can summarize what was observed among treated participants, but it cannot supply the randomized treatment contrast that a control group would allow. Descriptive frequency and comparative effect are different statistical quantities. Keeping that distinction clear prevents a within-group result from being overstated as a between-group treatment effect.

The record illustrates why analysis populations and missing-data procedures matter for binary outcomes. The Safety Set is named, but the endpoint denominator and handling of unavailable measurements are not reported. Without those details, the population represented by a hypothetical percentage and the contribution of missing observations would be unclear. These are essential elements for assessing an estimate, not merely administrative details.

Finally, planning assumptions should not be mistaken for evidence about the observed result. Sample-size illustrations are conditional calculations, not observed power and not a substitute for an endpoint estimate. In this case, the planning assumptions describe a two-arm equal-allocation scenario, whereas the registered study is single group. That difference reinforces the need to interpret planning calculations according to their assumptions and the actual study design.

15. 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 most direct limitation in the registry record is that it does not report the primary endpoint percentage or its 95% confidence interval limits. The magnitude and precision of the main efficacy outcome therefore cannot be assessed. The record gives the endpoint definition and timing but not the numerical result needed to interpret it.

The study is described as single group, open label, and without a comparator. It cannot provide a randomized between-group estimate for the primary endpoint. The endpoint is assessed at a specified visit following 24 days of treatment, so the registry description does not establish outcomes at other times or the persistence of concentrations within the target range.

The registry identifies the Safety Set but does not report its detailed definition, the endpoint denominator, or how missing endpoint measurements were handled. It also does not provide participant-level data or enough detail to reproduce the primary analysis. A fuller statistical analysis plan, sample-size justification, and interim-analysis details are not reported in the registry record.

The safety information is limited to the recorded counts and the listed top serious-event term. Further details on event timing, relatedness, recurrence, and the broader distribution of adverse events are not reported in the information used. These limitations restrict the conclusions that can be drawn from both the efficacy and safety descriptions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dosing Validation Study of Oral Testosterone Undecanoate (TU, LPCN 1021). — NCT03242590.
• Registry record last updated 2019-10-23; status last verified 2019-10.
• Results first posted 2019-09-11.
• 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.

19. Record Summary

NCT03242590 is a completed Phase 3, multicenter, open-label, single-group study of oral testosterone undecanoate LPCN 1021 in adult hypogonadal men. The registry record lists 95 enrolled participants and describes dosing as 225 mg TU two times a day. The study began in 2016-12 and reached primary completion in 2017-03.

The primary endpoint was the percentage of participants in the Safety Set with a 24-hour average serum testosterone concentration within 300 to 1080 ng/dL at Visit 4, Day 24 ± 4 days, following 24 days of treatment. Although a 95% confidence interval is specified, the endpoint estimate and interval limits are not reported in the registry record. Safety entries list one serious adverse event, six participants with other adverse events, zero deaths, and Gastric Ulcer Hemorrhage as the top serious-event term at 1.1%. No comparator arm is described.