Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer (NCT01415960), a na phase 3 study. The primary outcome is Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168..

2. Clinical Question

This is a question about a laboratory threshold over specified follow-up assessments, not a comparison of two assigned treatments. The threshold is the endpoint’s definition of chemical castration; it is not, by itself, a measure of every clinical outcome associated with prostate cancer. The study also lists secondary assessments of luteinizing hormone, follicle-stimulating hormone, prostate-specific antigen, leuprolide concentration and timing, and safety.

The record identifies the study as Phase 3 and completed, with a start date of 2011-09 and primary completion in 2013-05. Those design and administrative details provide context, but they do not substitute for the missing primary endpoint results. Without reported outcome estimates, the central statistical question cannot be answered from the registry record.

3. Trial Design

This was a Phase 3, single-group study of leuprolide acetate 22.5 mg depot in people with prostate cancer. The registry record lists 163 enrolled participants and one intervention: leuprolide acetate 22.5 mg depot. The arm description states that it was administered twice, 3 months apart. The record lists no masking and gives allocation as NA.

Because the study has a single group, its primary endpoint is assessed within participants receiving the intervention rather than against a concurrent control group. This makes the endpoint descriptive of the observed group and follow-up. It does not provide a randomized estimate of the difference between leuprolide and another treatment, placebo, or no treatment. A before-and-after or historical comparison is not reported in the registry record.

The primary endpoint concerns testosterone at or below 0.5 ng/mL at Days 28, 84, and 168, with a stated aim of evaluating maintenance through Day 168. The record gives the endpoint timeframe as 168 days. Secondary outcomes include serum luteinizing hormone, follicle-stimulating hormone, prostate-specific antigen concentrations, leuprolide Cmax and Tmax, and safety endpoints.

The registry record marks the study as completed. It lists a start date of 2011-09 and a primary completion date of 2013-05. The sponsor is GP-Pharm. Detailed eligibility criteria, recruitment procedures, the number assessed at each endpoint visit, and the protocol’s statistical analysis plan are not reported in the registry record. The record also does not provide an explanation of the study’s design choices or sample-size justification.

These design features matter when reading any reported estimate. In a single-group study, a percentage meeting an endpoint describes the participants assessed under the study conditions. Without a concurrent comparison group, that percentage alone cannot separate an intervention-associated pattern from changes that might also occur over time or under other care. The registry record does not report a comparative effect estimate.

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 Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168., measured over 168 days.

The primary endpoint is the percentage of participants whose testosterone level was at or below 0.5 ng/mL on Days 28, 84, and 168. The registry record describes this threshold as defining chemical castration. Its stated purpose is to assess whether the threshold was maintained through Day 168, with no missing data at these key time points unless missingness was due to an event unrelated to the study drug, for participants described as ITT.

A threshold-based endpoint converts a laboratory measurement into a binary classification at each assessment: a participant’s level is either at or below the threshold or above it. Reporting the percentage meeting the threshold can make the endpoint easier to interpret than reporting only a distribution of continuous laboratory values. However, it discards information about how far a measurement lies from the threshold and how measurements vary within the group.

Assessments at multiple scheduled times address whether the threshold was reached or maintained at those particular times. They do not establish what happened between visits unless additional data and analyses are reported. The endpoint is specifically about testosterone, not a direct measure of symptoms, tumor response, survival, or quality of life. Those outcomes are not identified as the primary endpoint in the registry record.

The record specifies a 95% confidence interval as the dispersion measure, but it does not report the observed percentages or intervals. Consequently, the endpoint’s observed level and its precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

The primary outcome is a percentage based on a binary classification: testosterone at or below 0.5 ng/mL at a scheduled assessment. In general, a binary outcome records whether each assessed participant meets a defined condition. The percentage then summarizes how common that condition was in the analyzed group. It does not describe the size of a change in testosterone or the distribution of measurements among participants.

For a percentage to be interpreted, the numerator and denominator matter. The numerator is the number meeting the endpoint, while the denominator is the number included in the assessment. The registry record does not report those visit-specific counts or denominators. Enrollment of 163 is not interchangeable with the number assessed at any particular visit, so the observed percentages cannot be derived from enrollment.

How should the confidence interval be read?

The registry record identifies a 95% confidence interval as the measure of dispersion for the primary endpoint. In general, a confidence interval describes the statistical uncertainty around an estimate under a specified method and its assumptions. It helps readers distinguish a relatively precise estimate from one with substantial uncertainty. The interval does not measure all possible sources of bias, and it cannot correct for the absence of a comparison group.

The confidence interval values and the method used to calculate them are not reported in the registry record. It is therefore not possible to assess the reported precision, check the method, or compare the intervals across assessment days. A confidence interval should also be read alongside the point estimate and the denominator; none of the visit-specific primary results are reported in the registry record.

What does the single-group design allow?

In general, a single-group study can describe outcomes among participants receiving the study intervention. It does not provide a concurrent control estimate of what would have happened under a different intervention. A percentage meeting the threshold at a scheduled visit would therefore be an observed group outcome, not by itself an estimate of a treatment difference. This distinction matters even when the endpoint is objectively measured in a laboratory.

The record lists allocation as NA, masking as none, and the model as single group. It does not report a randomized comparison. The findings cannot be interpreted as a like-for-like comparison between intervention arms, and no comparative effect is reported in the registry record.

What can be inferred from assessments over time?

The endpoint is assessed on Days 28, 84, and 168. In general, repeated scheduled measurements can describe the outcome at those separate times. They do not automatically establish the course between visits or whether each participant met the threshold continuously. The primary endpoint description says the assessments were intended to demonstrate maintenance through Day 168, but the registry record does not report the observed results or a separate analysis of continuity between visits.

The endpoint is binary at each visit, while testosterone itself is measured on a continuous scale. Turning a measurement into a threshold classification can aid interpretation against a prespecified criterion, but it also treats values just on opposite sides of the threshold as different categories and values within the same category as equivalent for that endpoint. This is a general property of threshold outcomes, not a finding about the study’s observed measurements.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are described as planning assumptions, not as the trial’s own design or as observed power. The registry record does not report the sample-size justification used to plan this single-group study.

In general, a sample-size illustration asks how many participants might be needed under specified assumptions to detect a chosen effect with a target probability, or power. Such a calculation is conditional on assumptions about the effect, variability, allocation, and analysis. It is not evidence that an observed result is reliable, nor does it substitute for the results themselves. The record notes that the illustration assumes two arms even though this study is recorded as single-group; it should not be mistaken for the actual trial design.

For binary outcomes, an illustration depends on the assumed event proportions in the groups and the difference intended to be detected. The record’s description of a fraction of the observed effect is a planning convention. Because the primary endpoint results and illustration values are not reported in the registry record, no particular planning scenario or sample-size value can be interpreted.

Why do missing data and analysis populations matter?

In general, missing outcome measurements can change who contributes to an estimate and can affect its interpretation. The primary endpoint description states that maintenance was to be demonstrated with no missing data at the key time points, unless missingness was due to an event unrelated to the study drug, for ITT patients. This describes an intended condition but does not report how many measurements were missing or how the condition was applied in the analysis.

The detailed analysis population, missing-data procedure, and statistical analysis plan are not reported in the registry record. The number of analyses listed is 0. Without reported results and methods, readers cannot determine how incomplete follow-up affected the endpoint estimates or whether additional analyses were conducted.

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 Acetate 22.5 mg Depot")
n      <- c(161)
events <- c(158)
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 Acetate 22.5 mg Depot  161  158  98.1  94.7  99.6  94.7  99.4  94.7  99.3

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint involves assessments on Days 28, 84, and 168. When a study examines outcomes at multiple times or tests multiple hypotheses, multiplicity can affect how statistical evidence is interpreted. In general, multiplicity procedures may be used to control the chance of false-positive findings across a family of tests. Whether such a procedure was planned or used is not reported in the registry record. The record does not provide test results or a statistical analysis plan that would clarify how the three assessment times were handled together.

The primary endpoint description states that there should be no missing data at the key time points unless missingness was due to an event unrelated to the study drug, for participants described as ITT. This wording describes the endpoint’s intended missing-data condition; it does not report actual completeness, reasons for missingness, or how any missing observations were handled. The detailed definition of the analysis population is not reported in the registry record.

In general, missing-data assumptions matter because estimates based only on observed measurements may differ from estimates that would have been obtained if all measurements were available. The registry record does not identify an imputation method, sensitivity analysis, or other missing-data procedure. It also lists 0 analyses, so no analysis-level details are available.

The primary outcome percentages, confidence intervals, and visit-specific denominators are not reported in the registry record. As a result, neither the effect of missingness nor the handling of repeated assessments can be evaluated from the posted information.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: syncope (1.8%), congestive heart failure (0.6%), myocardial infarction (0.6%), diarrhea (0.6%), incarcerated inguinal hernia (0.6%).

The registry record lists one group, Leuprolide Acetate 22.5 mg Depot, with 163 at risk for serious adverse events and 12 affected. It lists 163 at risk for other adverse events and 141 affected. These are separate registry summaries; the figures should not be added together because the record does not say that the categories are mutually exclusive. Deaths are not reported in the registry record.

The listed serious adverse event terms and percentages are syncope, 1.8%; congestive heart failure, 0.6%; myocardial infarction, 0.6%; diarrhea, 0.6%; incarcerated inguinal hernia, 0.6%; and rectal bleeding, 0.6%. These entries describe the registry’s listed terms and percentages. They do not establish that every serious event is represented in this list, or how the events were assessed for relationship to the intervention.

In general, an adverse-event percentage is a descriptive summary of events in a defined group. It does not by itself show that an event was caused by the intervention. With no comparison group listed, these figures cannot quantify an excess or reduced risk relative to another treatment or control condition. The registry record does not report further event-level details, such as timing, severity beyond the serious-event classification, or attribution.

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

The record identifies a study of leuprolide acetate 22.5 mg depot in prostate cancer and defines a primary laboratory endpoint: the percentage of participants with testosterone at or below 0.5 ng/mL at Days 28, 84, and 168. It states that the endpoint was intended to assess maintenance through Day 168. These details clarify what the study set out to measure.

The record does not report the observed primary endpoint percentages, their 95% confidence intervals, or visit-specific denominators. It therefore does not show how often participants met the threshold or how precisely that frequency was estimated. A completed-study status is not a substitute for outcome results, and the enrollment figure cannot be used to infer the number with available measurements at each visit.

Even if the outcome percentages were available, the single-group design would limit causal interpretation. In general, an outcome observed in one group does not reveal what would have happened to the same population under a different treatment or without the intervention. The registry record does not list a concurrent comparison group, so it does not support a randomized treatment-effect estimate.

The primary endpoint is a biochemical threshold outcome. It should not be conflated with clinical outcomes that are not identified as the primary endpoint, such as symptoms, survival, or quality of life. Secondary outcomes are listed for hormone measurements, prostate-specific antigen, leuprolide concentration and timing, and safety, but their results are not reported in the registry record.

The safety figures are descriptive and likewise do not provide a comparative safety estimate. Overall, the registry record describes the intervention schedule, endpoint definition, and selected safety summaries, but it does not report enough primary outcome information to establish the observed endpoint result or its precision. No conclusion about treatment benefit or lack of benefit follows from the outcome definition alone.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry record specifies the testosterone threshold, assessment days, and intended follow-up period. Those details make the target measurement understandable, but without the observed percentages, confidence intervals, and denominators, readers cannot judge the actual outcome level or its precision.

The trial also shows why design context belongs alongside an outcome estimate. A single-group study can provide a description of outcomes among participants receiving the intervention. It cannot, by itself, estimate how those outcomes compare with a concurrent control group. The record’s allocation and masking entries, together with its single-group model, are essential context for interpreting the question the study can address.

Scheduled measurements raise questions about repeated assessment and missingness. An outcome recorded at specific visits describes those times; it does not automatically establish what happened between visits. The endpoint description identifies a condition concerning missing key assessments, but the registry record does not report actual missingness or the methods used to address it. This leaves important uncertainty about the analysis population and the completeness of follow-up.

Finally, planning calculations and safety summaries should not be confused with primary results. A sample-size illustration based on assumptions is not observed power or evidence of an effect, while adverse-event counts from one group are not comparative risk estimates. The record’s limited results detail makes careful separation of design, analysis, and interpretation particularly important.

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 immediate limitation is that the registry record does not report the primary endpoint results. It gives the endpoint definition and specifies a 95% confidence interval, but the observed percentages, intervals, and assessment-specific denominators are not reported. This prevents evaluation of the endpoint’s magnitude and precision.

The study is listed as single-group, with allocation as NA and masking as none. No like-for-like control comparison is available in the record. Any outcome percentage would describe the observed study group; the design does not provide a randomized estimate of a difference against another treatment or control.

The record does not report the detailed eligibility criteria, the number assessed at each visit, the analysis population definition, or the actual missing-data pattern. Although the endpoint description refers to ITT patients and gives a condition for missing key time points, the registry record does not state how that condition was applied or what procedures were used for missing observations. The statistical analysis plan and multiplicity approach are also not reported.

The primary endpoint is a threshold-based testosterone measure at scheduled assessments. It does not, by itself, cover outcomes such as symptoms, survival, or quality of life. The listed secondary outcomes are not accompanied by results in the registry record. The safety summary is also limited: deaths are not reported, and the available adverse-event figures do not give a comparison group or further event-level context.

The sample-size information is described as a planning illustration based on assumptions, not as the trial’s own design. The registry record does not report the study’s sample-size justification. These omissions limit both statistical interpretation and the amount of context available for understanding the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer — NCT01415960.
• Registry record last updated 2017-03-03; status last verified 2016-11.
• Results first posted 2017-01-18.
• 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 NCT01415960, a completed Phase 3 single-group study sponsored by GP-Pharm. The study enrolled 163 people with prostate cancer and assessed leuprolide acetate 22.5 mg depot administered twice, 3 months apart. Masking is listed as none and allocation as NA. The recorded start date is 2011-09, with primary completion in 2013-05.

The primary endpoint is the percentage of participants with testosterone at or below 0.5 ng/mL on Days 28, 84, and 168, with a stated aim of assessing maintenance through Day 168. A 95% confidence interval is specified, but primary outcome values and intervals are not reported in the registry record. Secondary outcomes include hormone and prostate-specific antigen measures, leuprolide concentration and timing, and safety endpoints.

The record lists serious and other adverse-event summaries for the intervention group. It does not report a control comparison, a detailed statistical analysis plan, or the primary endpoint results needed to assess the observed outcome.