Phase II Study of Subcutaneous Injection Depot of Leuprolide Acetate in Patient With Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Subcutaneous Injection Depot of Leuprolide Acetate in Patient With Prostate Cancer (NCT02212197), a randomized phase 2 study. The primary outcome is Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3.

2. Clinical Question

The clinical question is primarily pharmacokinetic: what maximum serum leuprolide concentrations were observed after the first and third doses of the investigational depot, in the context of an active-control group? The study also listed testosterone recovery, testosterone concentration profiles and prostate specific antigen concentration as secondary outcomes. These measures address other aspects of drug exposure and response, but their numerical results are not reported in the registry record.

3. Trial Design

This was a phase II, randomized, open-label, active-control, parallel-group study. It enrolled 51 participants with prostate cancer and is recorded as completed. The study was multinational and multicentre according to its official title. Its stated purpose was to assess pharmacokinetics, pharmacodynamics, efficacy and safety of CAM2032 compared with Eligard. The registry record gives a start date of 2014-09 and a primary completion date of 2015-11.

Participants were assigned to one of three groups: CAM2032 3.75 mg, CAM2032 7.5 mg, or Eligard 7.5 mg. Each regimen involved a single subcutaneous buttock injection on Days 0, 28 and 56. The brief study description characterizes treatment as once monthly during 3 months. Recorded randomized group counts were 19 for CAM2032 3.75 mg, 15 for CAM2032 7.5 mg and 17 for Eligard 7.5 mg.

Randomized allocation means participants were assigned among the study groups by a random process, but the registry record does not describe how the sequence was generated or concealed. The study was unmasked, so participants and study personnel were not blinded according to the record. Whether laboratory personnel assessing serum concentrations were masked is not reported in the registry record. Because the primary outcome is a measured serum concentration, the endpoint is not a subjective rating; nevertheless, open-label status is part of the study context and may matter for other types of assessment or study conduct.

The primary endpoint was assessed over 84 days, with Cmax derived for Dose 1 and Dose 3 from serum leuprolide concentration profiles. The protocol description says blood samples were collected at predetermined time points, with full pharmacokinetic profiles after those doses. The registry record specifies the Per-Protocol Set for the primary outcome, defined as randomized participants in the safety population with a complete pharmacokinetic profile. It reports that 15 of 19 randomized participants in the CAM2032 3.75 mg group were included in that set; corresponding counts for the remaining groups are not reported in the registry record.

The registry lists six outcome measures and three secondary outcome titles. It does not report a statistical analysis plan, detailed randomization methods, or numerical primary-endpoint results. The design can therefore be described from the registered features, but the analysis procedures and the results needed to assess between-group differences cannot be reconstructed from this record alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Per-Protocol Set (PPS) consisted of all randomized participants in the safety population who had a complete PK profile. In the CAM2032 3.75 mg group 15 of the 19 randomized participants were included in the PPS.

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 Observed Maximum Serum Leuprolide Concentration (Cmax) for Dose 1 and Dose 3, measured over 84 days.

The primary endpoint was observed maximum serum leuprolide concentration, or Cmax, for Dose 1 and Dose 3. Cmax is the highest measured concentration in a pharmacokinetic profile following a dose. It describes the peak level observed during the sampling period; it does not, by itself, describe how long concentrations remain elevated or the total exposure over time. Other pharmacokinetic measures would be needed to characterize those different features.

Serum leuprolide concentrations were collected at predetermined time points during the trial, and full profiles were obtained after Dose 1 and Dose 3. The endpoint was defined over 84 days and reported as a geometric mean with geometric coefficient of variation as the dispersion measure. These summaries are commonly used for concentration measurements because pharmacokinetic values can be positively skewed: a geometric mean summarizes values on a multiplicative scale, while the geometric coefficient of variation describes relative spread on that scale. This is general statistical context, not a claim about the observed distribution in this study.

Cmax is useful for describing peak systemic exposure after a dose and for comparing concentration profiles across regimens. The first and third doses can represent different dosing occasions, so keeping the dose-specific results distinct is important. The registry record does not report the arm-specific geometric means, geometric coefficients of variation, confidence intervals or tests for this endpoint. Therefore, the endpoint definition can be interpreted, but the magnitude and precision of any group differences cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design and endpoint permit a discussion of the statistical ideas relevant to interpretation, but the registry record does not describe the full analysis methods. The explanations below distinguish general statistical principles from details that are actually reported for this trial.

What does randomization contribute?

In general, random assignment is intended to make the study groups comparable, on average, with respect to both measured and unmeasured participant characteristics at the time of assignment. This supports a causal interpretation of a properly conducted between-group comparison. Randomization does not guarantee that the realized groups are identical, especially in a study with 51 participants, and it cannot correct problems arising from missing outcomes, post-randomization exclusions or an unsuitable analysis. The registry record states that allocation was randomized, but the sequence-generation and concealment methods are not reported in the registry record.

The study was open label and used parallel groups. In a parallel design, participants remain in their assigned group rather than crossing between regimens. Open-label status means masking was absent according to the registry record. For a laboratory concentration outcome, the outcome is a measured quantity rather than a participant-reported judgment, but masking of laboratory staff is not described. General concerns about open-label conduct can also apply to follow-up, decisions about assessments and outcomes that require judgment; the registry record does not state whether any such processes influenced this study.

Why use a geometric mean?

The primary outcome is described as a geometric mean with geometric coefficient of variation. In general, concentration data may have a right-skewed distribution, with some observations substantially larger than others. A geometric mean is calculated through the log scale and represents a central value for multiplicative data. The geometric coefficient of variation expresses dispersion relative to the geometric mean, rather than as an additive standard deviation. These summaries can be appropriate when proportional differences are more meaningful than absolute differences. They do not show the full distribution, and their interpretation depends on the measurements and analysis population. The registry record does not report the observed summaries or state whether a particular transformation or model was used.

Cmax is the maximum observed concentration in a profile. The observed maximum can depend on when blood samples are taken: if the true peak falls between scheduled sampling times, the measured maximum may differ from the unobserved peak. The registry record describes predetermined sampling times and full profiles after Dose 1 and Dose 3, but does not report the exact schedule or methods for handling concentrations below quantification limits. Those details are not reported in the registry record.

What does a confidence interval tell the reader?

Generally, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval for a between-group contrast would help show which effect sizes remain compatible with the data, rather than reducing interpretation to whether a significance threshold was crossed. No confidence intervals or Cmax contrasts are reported in the registry record, so the precision of the primary result cannot be described.

A p-value, in general, measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were correct. It does not measure the probability that the null hypothesis is true, the probability that a result is due to chance, or the importance of an observed difference. A p-value also does not convey the size or precision of an effect. The registry record does not report a p-value for the primary endpoint or a detailed statistical testing plan.

How should the analysis population be understood?

The primary outcome population is the Per-Protocol Set, defined as randomized participants in the safety population who had a complete pharmacokinetic profile. This definition makes completeness of the profile part of inclusion in the primary analysis. The record states that 15 of the 19 randomized participants in the CAM2032 3.75 mg group were included. The other groups' Per-Protocol Set counts, reasons for incomplete profiles, and any sensitivity analyses are not reported in the registry record.

In general, an analysis restricted to participants who meet post-randomization criteria may no longer preserve all the protections of randomization. If profile completion is related to participant characteristics or outcomes, estimates in the included participants may differ from estimates in all randomized participants. This is a general methodological concern, not evidence that such bias occurred in this trial. An analysis of all randomized participants, an analysis of the safety population, or sensitivity analyses could address different questions, but the analysis populations and methods beyond the defined Per-Protocol Set are not reported in the registry record.

What can planning calculations say?

Sample-size calculations are planning tools. The registered assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event calculations, the illustration is based on the total number of events, while other calculations express participants per arm. These assumptions describe a planning framework, not the original trial's design justification. The protocol's sample-size justification is not reported in the registry record.

Such an illustration is not observed power and cannot establish that a study had a particular probability of detecting a real effect. An effect estimated in a study is uncertain, and calculations tied to that observed effect inherit that uncertainty. The numerical planning results and the stated effect fraction are not reported in the registry record. Therefore, no planning count or target can be interpreted from the registry record alone.

More broadly, the statistical analysis plan, model specification, covariate adjustment, treatment of repeated measurements and multiplicity procedures are not reported in the registry record. These omissions limit assessment of whether the analyses matched the endpoint structure and how strongly the reported results, if available, would support a particular interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the primary Cmax endpoint and secondary outcomes concerning time to testosterone recovery after Dose 3, testosterone concentration profiles and mean prostate specific antigen concentration. It does not report a multiplicity strategy. When a study evaluates several outcomes, doses or time points, testing each separately can increase the chance of at least one apparently unusual result even when there is no underlying difference. General approaches include prespecifying a hierarchy of outcomes or adjusting interpretation for multiple tests. Which, if any, approach was used in this trial is not reported in the registry record.

The primary endpoint includes Cmax after Dose 1 and Dose 3, which are distinct assessment occasions. The registry record does not say whether these were treated as separate tests, combined into one analysis, or interpreted under a prespecified hierarchy. It also does not report how comparisons among the three groups were organized. Without that information and without numerical endpoint results, neither the number of statistical tests nor their joint interpretation can be assessed.

Missing-data handling is also not described. The primary analysis population required a complete pharmacokinetic profile, and the record reports that 15 of the 19 randomized participants in the CAM2032 3.75 mg group entered that set. It does not give corresponding counts for the other groups, reasons for missing profiles, or methods for handling partial data. These details matter because missingness can influence which participants contribute to an estimate. No imputation method, sensitivity analysis or comparison of included and excluded participants is reported in the registry record.

The Per-Protocol Set is defined, but the registry record does not describe an intention-to-treat analysis or identify additional analysis populations for the primary endpoint. Nor does it explain how deviations from the assigned regimen, if any, were handled. These omissions do not demonstrate that the analysis was inappropriate; they mean the analysis population and robustness of the results cannot be fully evaluated from the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disorientation (6.7%), calculus urinary (6.7%), urinary tract infection (6.7%).

The registry reports serious adverse events and other adverse events by group. For serious adverse events, the recorded counts were 0 of 19 participants in CAM2032 3.75 mg, 1 of 15 in CAM2032 7.5 mg and 0 of 17 in Eligard 7.5 mg. For other adverse events, the counts were 14 of 19, 12 of 15 and 10 of 17, respectively. These are participant counts within the registry's categories; they do not establish that an event was caused by a study regimen.

The record lists Disorientation, Calculus urinary and Urinary tract infection as top serious-event terms, each reported as 6.7%. It does not identify the group associated with each listed term in the information, so the terms should not be assigned to a particular arm. The death counts are not reported in the registry record.

Adverse-event counts describe how many participants were recorded with events; they do not alone show event severity over time, duration, recurrence, or causal attribution. Differences in counts across groups should be interpreted cautiously, particularly without a statistical comparison or further detail about event definitions and follow-up. The registry record does not report a formal safety comparison or additional context needed to assess individual events.

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

The record establishes that a randomized phase II study was conducted in participants with prostate cancer, comparing two CAM2032 doses with Eligard 7.5 mg. It describes monthly subcutaneous dosing on Days 0, 28 and 56, and identifies observed maximum serum leuprolide concentration after Dose 1 and Dose 3 as the primary endpoint. It also reports some adverse-event counts and names secondary outcomes.

It does not report the numerical primary-endpoint findings. Without the arm-specific Cmax estimates and their variability, the record cannot show the magnitude or direction of any difference among the three groups. Without confidence intervals or other uncertainty measures, it cannot show how precisely a difference was estimated. The absence of these results is not evidence that the regimens had identical concentrations, nor evidence that one regimen had higher or lower concentrations.

The record also does not report numerical results for the listed secondary outcomes. Thus, it cannot establish from the posted results what the testosterone concentration profiles, time to testosterone recovery or mean prostate specific antigen findings were. Nor can the reported adverse-event counts determine whether any observed event was caused by an assigned regimen. Safety counts are descriptive and are not a substitute for outcome-specific comparative analyses.

The registered design has useful features for a comparative study: random allocation, parallel groups and an active control. Interpretation still depends on the actual estimates, completeness of follow-up, analysis populations, missing-data methods and prespecified comparisons. Several of those details are not reported in the registry record. The stated Per-Protocol Set definition and partial inclusion count are relevant because a complete-profile requirement can leave some randomized participants out of the primary analysis; the record does not explain the reasons or give corresponding counts for every group.

Accordingly, the study record supports a description of the research question and design, but not a conclusion about comparative pharmacokinetic results. It also does not establish clinical benefit or lack of benefit. The numerical findings and analysis details needed to make those judgments are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a well-defined outcome and an interpretable result. Cmax is specified as the primary measure, the dose occasions are identified, and the summary scale is described. Those details clarify what investigators intended to estimate. Yet a measurement definition alone cannot answer the comparative question: readers also need the arm-specific estimates and a measure of their uncertainty.

The design includes two investigational dose groups and an active control, which creates more than one possible comparison. The registry record does not describe how those comparisons were prioritized or how multiple tests were handled. This makes the analysis plan important to interpretation, particularly when a primary endpoint includes measurements after more than one dose. Without the planned comparison structure and numerical results, the evidence cannot be summarized as a single direction or effect.

The Per-Protocol Set definition also highlights a recurring issue in clinical trials: the population used for analysis may differ from the group originally randomized. Complete pharmacokinetic profiles may be necessary for a particular estimate, but missing profiles can affect both precision and comparability. Reporting group-specific analysis counts, reasons for missing data and sensitivity analyses helps readers judge whether conclusions are robust. The registry record gives one group's inclusion count but does not report the corresponding details for the other groups.

Finally, adverse-event counts and pharmacokinetic outcomes answer different questions. Descriptive safety counts do not supply evidence about the primary concentration endpoint, while a concentration endpoint alone cannot characterize all aspects of safety or clinical outcomes. Keeping those distinctions clear prevents an incomplete registry record from being read as a broader efficacy conclusion.

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.

A central limitation for interpreting this specific record is that numerical results for the primary endpoint are not reported in the registry record. The record identifies Cmax after Dose 1 and Dose 3, but supplies no group estimates, dispersion values, confidence intervals or tests. Results for the listed secondary outcomes are also not reported. As a result, the comparative pharmacokinetic question remains unanswered by the information in the registry record.

The primary endpoint analysis was defined for the Per-Protocol Set, which required a complete pharmacokinetic profile. The record reports inclusion of 15 of the 19 randomized participants in the CAM2032 3.75 mg group, but not the equivalent counts in the other groups or the reasons for incomplete profiles. It also does not describe missing-data methods or sensitivity analyses. These gaps prevent assessment of how much the primary analysis population differed across groups or how sensitive an estimate might be to missing measurements.

The trial was open label. The record does not report masking of laboratory personnel or detail how outcome assessment was conducted. It also does not describe sequence generation or allocation concealment. These are reporting gaps, not proof that bias occurred, but they limit evaluation of safeguards around randomization and measurement.

The registry record does not report a statistical analysis plan, multiplicity procedures, model details, covariate adjustment or the planned structure of comparisons among the three groups and two dose occasions. It gives no protocol sample-size justification. The sample-size assumptions describe a planning illustration, but numerical planning outputs and the effect fraction are not reported in the registry record. These omissions constrain evaluation of whether the study was planned and analyzed for a particular precision or comparison.

Enrollment was 51, and the primary endpoint was assessed over 84 days. Those details describe the scale and timeframe of the study, but do not by themselves quantify the precision of any result. The registry's serious adverse-event counts also lack reported death counts and detailed comparative analysis. These limitations should be kept distinct from the design features that are documented.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Study of Subcutaneous Injection Depot of Leuprolide Acetate in Patient With Prostate Cancer — NCT02212197.
• Registry record last updated 2017-04-25; status last verified 2017-03.
• Results first posted 2017-02-06.
• 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

NCT02212197 is a completed phase II, randomized, open-label, active-control, parallel-group study in participants with prostate cancer. Total enrollment was 51. The groups received CAM2032 3.75 mg, CAM2032 7.5 mg or Eligard 7.5 mg as subcutaneous buttock injections on Days 0, 28 and 56. The primary endpoint was observed maximum serum leuprolide concentration after Dose 1 and Dose 3, summarized as a geometric mean with geometric coefficient of variation over 84 days.

The primary analysis population was the Per-Protocol Set, defined by randomization, inclusion in the safety population and a complete pharmacokinetic profile. The registry record reports inclusion of 15 of 19 randomized participants in the CAM2032 3.75 mg group. It reports adverse-event counts by group, but does not report numerical Cmax results, secondary-outcome results, a detailed statistical analysis plan, or death counts. Consequently, comparative primary-endpoint effects and their precision cannot be determined from the registry record.