Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate (LMIS 25 mg) in Subjects With Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate (LMIS 25 mg) in Subjects With Prostate Cancer (NCT03261999), a na phase 3 study. The primary outcome is Efficacy of Leuprolide Mesylate (LMIS 25mg).

2. Clinical Question

3. Trial Design

This is a phase 3, open-label, single-arm study of leuprolide mesylate in males with prostate cancer. The registry record reports enrollment of 144 participants. All participants were assigned to the same intervention: a depot formulation containing 25 mg of leuprolide mesylate, administered as two injections. The first dose was scheduled for Day 0 and the second for Day 84, twelve weeks apart, with follow-up until Day 168.

Because the design has one group, there is no randomized comparison and no concurrent control group described in the registry record. Allocation is recorded as not applicable, and masking as none. The design can describe outcomes observed among participants receiving the intervention, but by itself it cannot separate changes associated with treatment from changes that might have occurred over time or for other reasons. That limitation is important when interpreting any outcome as evidence of comparative effect.

The study title and summary refer to safety, efficacy, and pharmacokinetic behavior. The primary outcome is the percentage of participants whose serum testosterone was suppressed to castrate levels from Day 28 through Day 168. The listed secondary outcome concerns participants with adverse events. Specific pharmacokinetic endpoints and their numerical results are not reported in the registry record.

The study is marked completed. Its recorded start date is 2017-09-26, and primary completion is recorded as 2018-11-19. Further details about eligibility criteria, recruitment procedures, follow-up completeness, and the statistical analysis plan are not reported in the registry record. The registry record also does not describe an active comparator, placebo group, or a parallel control group.

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: ITT (one subject had missing time point at Day 28)

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 Efficacy of Leuprolide Mesylate (LMIS 25mg), measured over 168 days.

The primary endpoint is the percentage of participants whose serum testosterone concentration was suppressed to castrate levels, defined as at or below 50 ng/dL, from Day 28 through Day 168. The registry record gives the timeframe as 168 days and identifies the analysis population as ITT, noting one subject had a missing time point at Day 28. The numerical endpoint result and its 95% confidence interval are not reported in the registry record.

As a general statistical concept, a percentage expresses how common a specified outcome was within the group being assessed. Here, the outcome is a laboratory threshold response over the stated interval. This endpoint is used to characterize whether the targeted testosterone suppression was observed in participants during follow-up; it is not itself a direct measure of every aspect of disease status or a comparison with another treatment.

The timeframe matters to interpretation. An endpoint spanning Day 28 through Day 168 describes response across a period rather than a single isolated measurement, although the registry description does not explain the detailed rule for classifying a participant across repeated measurements. That operational detail is not reported in the registry record. Nor are the number of participants meeting the endpoint, the estimation method, or the confidence interval reported. Without those results, neither the observed proportion nor its statistical precision can be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary percentage represent?

The primary outcome is a binary response summarized as a percentage: each participant is classified according to whether serum testosterone was suppressed to castrate levels, at or below 50 ng/dL, from Day 28 through Day 168. In general, a percentage is a way to describe the share of an assessed group meeting a defined criterion. Its interpretation depends on the criterion, the participants included, and how incomplete measurements are handled. The registry record gives the criterion and describes the population as ITT, but it does not give the observed percentage or explain the detailed classification rule across measurements.

What would a confidence interval tell a reader?

The registry identifies the dispersion measure for the primary endpoint as a 95% confidence interval, but the interval itself is not reported in the registry record. In general, a confidence interval conveys the statistical uncertainty around an estimated quantity, under the assumptions of the method used. For a percentage, it helps readers distinguish a relatively precise estimate from one with substantial uncertainty. The interval does not correct for limitations of a single-arm design, missing data, measurement procedures, or other sources of bias. Without the endpoint estimate and interval, the precision of the primary result cannot be judged.

What does the single-arm design permit?

The trial has one intervention group and no comparator. In general, a single-arm study can describe the outcomes observed among participants receiving the intervention. It does not directly estimate a treatment contrast against a concurrent comparison group. A before-and-after or threshold-based outcome may be useful for describing the enrolled group, but observed change or response alone does not establish what would have happened under a different treatment or without treatment. The registry record gives no randomized control results, so comparative interpretation is not available.

How should the adverse-event counts be read?

The record lists counts of participants at risk and participants affected for serious and other adverse events. In general, such counts describe the frequency of recorded events in the study group. They do not, by themselves, establish causality. Interpretation may also depend on event definitions, collection methods, duration of observation, and whether participants can contribute more than one event. Those details are not reported in the registry record. The serious-event terms are listed with percentages, but the record does not provide further event-level detail or a comparator rate.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration, not the trial’s observed power. The stated framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. In general, a planning calculation estimates the sample size that might be needed under specified assumptions. It is conditional on those assumptions and is not evidence that a study had a given probability of finding a result. The record does not report the trial’s own sample-size justification, and no planning estimate values are included in the registry record. The trial itself is single-arm, while the described illustration assumes equal allocation between two arms; that planning framework should not be mistaken for the trial design.

What statistical details remain unavailable?

The registry record does not report the numerical primary endpoint result, its confidence interval, or analysis outputs. It does not provide the statistical model or method used to calculate the endpoint, explain any adjustment, or specify a missing-data strategy. The record also does not report an interim analysis plan or the trial’s own sample-size justification. These omissions limit independent assessment of how the endpoint was estimated and how robust the result may be to alternative reasonable analytic choices.

As a general principle, methods should be read in relation to the outcome’s scale and the way observations were collected. A binary endpoint is often summarized by a proportion and an uncertainty interval, while repeated measurements can require a prespecified rule for translating measurements over time into a participant-level outcome. The registry description names a period from Day 28 through Day 168 but does not explain whether every measurement in that period had to meet the threshold, how gaps were handled, or how a participant with an incomplete series was classified. Those rules are not reported in the registry record and should not be assumed.

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("Leuprolide Mesylate 25mg")
n      <- c(143)
events <- c(140)
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  Leuprolide Mesylate 25mg  143  140  97.9  94.0  99.6  94.0  99.3  94.0  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and a secondary outcome concerning the number of participants with adverse events. It does not report a multiplicity strategy, such as whether formal testing across multiple outcomes was planned or how any resulting error rate would be controlled. The number of analyses is recorded as 0, and no inferential analysis results are reported. Details of any hierarchy or prespecified testing sequence are not reported in the registry record.

Missing-data information is limited. The primary population is described as ITT, with one subject having a missing time point at Day 28. The record does not state whether that participant was excluded from a particular calculation, counted as not meeting the endpoint, or handled using another method. It also does not report whether measurements were missing at other time points or how any such missingness was treated. A missing-data strategy and sensitivity analyses are not reported in the registry record.

In general, missing measurements can affect an estimated percentage when the outcome status of participants with incomplete data is uncertain. The impact depends on how many observations are missing, why they are missing, and the analysis approach. A single-arm study also has no comparison group against which to evaluate patterns of missingness or outcome differences. These general concerns cannot be resolved from the record’s brief note about one missing Day 28 time point.

The analysis population is named, but additional population definitions and analysis-set rules are not reported in the registry record. The primary endpoint result itself is also not reported. Consequently, readers cannot check the effect of the missing time point, the relationship between analysis populations, or the impact of multiplicity decisions on any reported statistical conclusion.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (0.7%), pancreatitis acute (0.7%), drug-induced liver injury (0.7%), tendon rupture (0.7%), basal cell carcinoma (0.7%).

For the leuprolide mesylate 25mg group, the registry record lists 144 participants at risk for serious adverse events and 9 participants affected. It lists 144 participants at risk for other adverse events and 70 participants affected. Deaths are recorded as 0. These are counts from the study group, not comparisons with another group.

The listed serious adverse event terms are acute myocardial infarction, pancreatitis acute, drug-induced liver injury, tendon rupture, basal cell carcinoma, and oropharyngeal neoplasm. Each is reported as 0.7%. The registry record does not give additional event-level information, such as timing, severity beyond the serious classification, clinical course, or whether the events were considered related to treatment. The listed terms should therefore be read as reported safety entries, not as evidence that the intervention caused them.

In general, adverse-event counts describe what was recorded during study observation; they do not alone establish risk relative to an alternative. The record does not provide a control-group rate, and it does not provide further details about event collection or exposure duration beyond the study follow-up to Day 168. The counts are informative as descriptions of this enrolled group, but they cannot support a comparative safety estimate on their own.

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

The record describes a completed phase 3 study in which 144 males with prostate cancer received leuprolide mesylate as two injections twelve weeks apart, followed through Day 168. Its primary endpoint was the percentage with serum testosterone suppressed to castrate levels from Day 28 through Day 168. That outcome is a defined laboratory response, and the registry record also lists adverse-event information.

What the primary result means cannot be assessed numerically because the endpoint percentage and its 95% confidence interval are not reported in the registry record. The record therefore does not show how many participants met the endpoint, how uncertain an estimate was, or whether a statistical analysis supported a particular conclusion. The study title and summary state that safety, efficacy, and pharmacokinetic behavior were evaluated, but numerical pharmacokinetic results are not reported in the registry record.

The design also limits what can be concluded. With a single treatment group and no comparator, the record can describe outcomes in participants who received the intervention, but it cannot provide a randomized estimate of the difference versus another treatment or no treatment. A single-group outcome does not isolate the intervention’s contribution from other influences on outcomes over time.

The adverse-event counts and listed serious-event terms provide a description of reported safety observations in this study group. They do not establish that the intervention caused an event or indicate how the counts compare with another group. The registry record does not include the detail needed to interpret event timing or attribution.

Thus, the record identifies the treatment schedule, follow-up period, primary endpoint definition, and some safety counts, while leaving the primary numerical outcome and its precision unavailable. It does not support a comparative claim about efficacy or safety. These are limits of what can be inferred from the registry record, rather than conclusions about outcomes not reported there.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported numerical estimate are both important. The primary outcome specifies a laboratory threshold and a follow-up interval: testosterone at or below 50 ng/dL from Day 28 through Day 168. That definition makes the intended response understandable. But without the observed percentage and its confidence interval, a reader cannot assess either the result’s magnitude or its statistical precision.

The design is equally important to statistical interpretation. An open-label, single-arm study provides observations from participants receiving one intervention, but it has no concurrent comparator. This means there is no direct randomized contrast in the registry record. Statistical interpretation must keep that design limitation separate from the definition of the endpoint or the size of the enrolled group.

The record also demonstrates the value of reporting how missing measurements are handled. It notes one missing Day 28 time point in the ITT population, but does not state how this observation was treated or whether other measurements were missing. In general, transparent missing-data methods help readers understand which participants contributed to an estimate and how incomplete observations may affect it.

Safety reporting is another distinct statistical task. Counts of affected participants and named serious events describe what was recorded, while causal attribution and comparison require additional evidence and detail. The registry lists safety counts but does not give a comparator rate or event-level context.

Finally, planning calculations must not be confused with trial results or observed power. The registry describes assumptions for planning illustrations, while the actual study is single-arm. Keeping design, endpoint, missing-data handling, and planning assumptions distinct helps prevent an incomplete registry entry from being read as a complete statistical evaluation.

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 consequential limitation for interpreting efficacy is that the registry record does not report the numerical primary endpoint result or its confidence interval. Although the endpoint is defined, the observed proportion and its precision cannot be evaluated. The record also does not report a statistical analysis output or method for estimating the endpoint.

The study is open-label and single-arm, with no comparator group. As a result, the registry record contains no randomized between-group comparison. This restricts conclusions to describing the intervention group and prevents direct assessment of relative effects from the posted record. The absence of a comparator also limits interpretation of adverse-event counts as comparative safety evidence.

The missing-data note says that one subject had a missing time point at Day 28, but the registry record does not explain how that observation was handled. The endpoint spans Day 28 through Day 168, yet the operational rule for classifying response across the interval is not reported. Other details about endpoint measurement completeness and follow-up are not reported in the registry record.

The title refers to pharmacokinetic behavior, but specific pharmacokinetic outcomes and numerical results are not reported in the registry record. The record also does not report the trial’s own sample-size justification, a multiplicity strategy, interim analyses, or a detailed statistical analysis plan. These gaps prevent assessment of whether the posted endpoint analyses followed prespecified procedures or how multiple outcomes were addressed.

Safety information is limited to counts and a list of serious adverse-event terms with percentages. Event timing, attribution, and fuller clinical descriptions are not reported in the registry record. These limitations are specific to the information available for this study and constrain interpretation of both its primary outcome and safety observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate (LMIS 25 mg) in Subjects With Prostate Cancer — NCT03261999.
• Registry record last updated 2020-05-04; status last verified 2019-02.
• Results first posted 2020-05-04.
• 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

The registry record describes NCT03261999, a completed phase 3, open-label, single-arm study of leuprolide mesylate in males with prostate cancer. Enrollment was 144. Participants were scheduled to receive two 25 mg depot injections, on Day 0 and Day 84, with follow-up until Day 168.

The primary endpoint was the percentage with serum testosterone suppressed to castrate levels, at or below 50 ng/dL, from Day 28 through Day 168. Its numerical result and 95% confidence interval are not reported in the registry record. The record notes one missing Day 28 time point in the ITT population.

Safety listings include 9 participants with serious adverse events, 70 with other adverse events, and 0 deaths among 144 at risk in each event category. Six serious-event terms are each listed at 0.7%. The study has no comparator group, and numerical pharmacokinetic results are not reported in the registry record.