Investigation of a New Trial Drug (FE200486) in Prostate Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of a New Trial Drug (FE200486) in Prostate Cancer Patients (NCT00818623), a randomized phase 2 study. The primary outcome is Time From Dosing Until Testosterone Levels >0.5 ng/mL.

2. Clinical Question

The study's stated purpose was to investigate dose selection, pharmacokinetics, pharmacodynamics, and safety. Participants received FE200486 on one occasion and attended follow-up visits according to a schedule until blood samples showed no further effect. The listed secondary questions include maintaining testosterone at or below 0.5 ng/mL for at least 28 days or 84 days, time to testosterone castration, time to reductions in prostate-specific antigen, liver function tests, and changes in vital signs and body weight.

The primary comparison is not a comparison of degarelix with another treatment. It asks whether the time-to-event distributions differ across the dose groups. The record also includes secondary pairwise re-calculations against the 120mg (20mg/mL) group for two binary testosterone outcomes. Those comparisons address different questions from the primary time-to-event analysis and should not be treated as substitutes for it.

3. Trial Design

This was a phase 2, randomized, open-label, multicenter, parallel and sequential ascending single-dose study. The registry record reports enrollment of 172 participants with prostate cancer and a completed status. The recorded study dates are 2002-11 for start and 2004-10 for primary completion. Ferring Pharmaceuticals is listed as the sponsor.

Eight degarelix regimens appear in the arm descriptions. They vary by dose and concentration: 120 mg at 20 mg/mL or 40 mg/mL; 160 mg at 40 mg/mL; 200 mg at 40 mg/mL or 60 mg/mL; 240 mg at 40 mg/mL or 60 mg/mL; and 320 mg at 60 mg/mL. Participants received treatment on one occasion, followed by scheduled visits and blood sampling. The record describes parallel groups and an ascending-dose study, but the exact allocation procedure and sequence details are not reported in the registry record.

Masking is listed as none, so the study was open-label. No separate placebo or active-comparator intervention is listed. Consequently, the posted results describe differences among degarelix regimens rather than treatment effects against an untreated group or a different medicine. The arm counts for the primary outcome vary, ranging from 12 to 25 participants per group; these are endpoint-specific counts and need not be identical to total enrollment.

The stated aims included pharmacokinetics, pharmacodynamics, dose selection, and safety. The registry record does not report a sample-size justification, detailed randomization procedures, interim analyses, or a complete statistical analysis plan. It lists 8 outcome measures and 22 analyses, while the posted results include a global log-rank test for the primary endpoint and global Kruskal-Wallis tests for the two posted binary testosterone endpoints. Details for outcomes and analyses not posted are not reported in the registry record.

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.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population.

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Time From Dosing Until Testosterone Levels >0.5 ng/mL, measured over 3 months.

The primary endpoint is the time from dosing until testosterone levels were greater than 0.5 ng/mL. The outcome is summarized by a median time in days and a 95% confidence interval for each dose group. The registry description specifies the ITT population and says that the endpoint is based on one testosterone value greater than 0.5 ng/mL from Day 28 onwards. The stated timeframe is 3 months.

In general, a time-to-event endpoint records how long it takes for a defined event to occur. Here the event is a measured testosterone value above the threshold, rather than a change in symptoms or a clinical event. A median time gives the point by which half of the relevant observed time-to-event distribution has reached the event, subject to how censoring and follow-up are handled. The registry record does not report those handling details.

Time-to-event methods can use information from participants whose event has not been observed by the end of follow-up, provided censoring information is available and the method's assumptions are appropriate. This can be useful when follow-up duration differs or some events are not observed. However, the endpoint's clinical interpretation depends on the stated threshold, measurement schedule, and analysis definitions. The record's operational definition uses a single value above the threshold from Day 28 onwards; it does not establish how a transient rise or missing scheduled blood sample was treated.

The endpoint is a pharmacodynamic measure of testosterone response after a single dose. It does not directly measure survival, tumor progression, quality of life, or a comparison with another treatment. Its results therefore answer a specific question about time to a laboratory threshold, not every question about prostate cancer outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, statistical methods should match the outcome type and the question being asked. This trial's primary endpoint is time to a defined laboratory event, while its posted secondary testosterone outcomes include counts of participants meeting a threshold-duration definition. Those outcomes require different summaries and tests. The registry record identifies the methods for the global analyses but does not provide a complete statistical analysis plan.

What does a median time summarize?

For a time-to-event outcome, the median is the time at which the estimated event-free proportion reaches the midpoint of its distribution. In this study, the event is a testosterone value greater than 0.5 ng/mL under the endpoint's specified definition. A median is less affected by extreme event times than a mean, but it does not describe the full shape of the time-to-event distribution. Two groups can have similar medians yet differ at other times, or have different medians with substantial uncertainty.

Each posted median is accompanied by a 95% confidence interval. In general, a confidence interval describes the uncertainty of an estimate under the analysis method: intervals that are wider indicate less precision. It is not a range containing a fixed proportion of individual participant outcomes. The registry record does not state how censoring, loss to follow-up, or incomplete testosterone measurements were handled, which limits independent assessment of the time-to-event estimates.

What does the log-rank test assess?

The reported log-rank test compares time-to-event experience across the eight groups over follow-up. In general, it uses the ordering of event times and can incorporate censored observations. Its global p-value tests whether the group distributions are compatible with a common time-to-event pattern under the test's assumptions. A small p-value is evidence against that global null hypothesis, but is not an estimate of the size of a difference and does not specify which groups differ. The reported value is < 0.001.

The log-rank test is not a dose-response test. Establishing a trend would require a prespecified trend analysis or an appropriate model that represents dose and concentration. The registry record does not report such an analysis. Moreover, changing concentration as well as dose in several regimens makes simple attribution to dose alone difficult. A hazard ratio is not posted for this primary result, and it should not be inferred from the medians or global test.

How should the binary outcomes be read?

The two posted secondary endpoints count participants who maintained testosterone at or below 0.5 ng/mL for at least 28 days or at least 84 days. For these outcomes, the posted arm summaries include counts and confidence intervals. In general, a binary outcome reduces each participant's information to whether a defined condition was met. That makes the result straightforward to describe, but it discards the timing and duration detail available in a time-to-event analysis.

The sponsor reports a Kruskal-Wallis test for each of these endpoints. The registry record gives global p-values of 0.001 and 0.003, respectively. In general, the Kruskal-Wallis test compares ranked observations across groups; the registry does not explain how the test was applied to these binary measures or provide its detailed analysis specification. A global result does not identify the pair or pairs responsible for group differences.

The two-arm comparisons against the 120mg (20mg/mL) group are recalculated from posted summary statistics. They include risk differences and confidence intervals, with unadjusted p-values. In general, the risk difference expresses the contrast between two observed proportions on the absolute probability scale. Its confidence interval communicates uncertainty, and an interval that includes zero is compatible with no difference under that calculation. These calculations are not a substitute for the sponsor's global analyses and are not adjusted for multiple comparisons.

What are the planning illustrations?

The sample-size illustrations are planning calculations based on the observed effect for selected binary comparisons. They assume a two-sided significance level of 0.05, equal allocation between the two groups, and a normal approximation. The rows express planning for 100%, 75%, or 50% of the observed effect, with separate figures for 80% and 90% power. They are hypothetical design illustrations, not observed power and not the enrollment rationale for this trial. The registry record does not report the trial's own sample-size justification. Because the observed effects come from small groups, planning directly from them may give an unstable picture of the effect a future study should target.

In general, over-dispersion means that variation in the data exceeds what a simple model assumes. It matters when a model's standard errors or confidence intervals depend on an understated variance. The posted outcomes do not report an over-dispersion analysis, and no such result should be inferred. Likewise, no adjusted hazard ratios, pairwise primary comparisons, or model-based dose trends are reported in the registry record.

10. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is a log-rank test across all eight degarelix groups, with p< 0.001. It addresses an overall time-to-event question. The posted primary group summaries give medians and 95% confidence intervals, but do not include sponsor-reported pairwise hazard ratios or pairwise comparisons. The global test therefore supports only a statement about evidence of differences somewhere among the group distributions, not which specific regimens account for that result.

The recalculated pairwise results in the secondary material concern different outcomes: the numbers of participants maintaining testosterone at or below 0.5 ng/mL for at least 28 days or 84 days. They compare two selected groups at a time against degarelix 120mg (20mg/mL), using unadjusted calculations from posted summary statistics. They are not re-analyses of the primary time-to-event outcome, and they should not be used to reinterpret the sponsor's global log-rank result.

There is no reported discrepancy between the posted material and the re-calculations. The sponsor's reported global tests remain the appropriate description of the analyses the sponsor reported, while the pairwise calculations provide supplementary, unadjusted contrasts. The secondary global Kruskal-Wallis results likewise answer an across-group question and do not validate every individual pairwise comparison. The registry record does not report multiplicity adjustments or a prespecified hierarchy connecting the primary and secondary tests.

11. Multiplicity, Missing Data and Analysis Populations

The registry record reports one global log-rank analysis for the primary time-to-event endpoint and global Kruskal-Wallis tests for the two posted duration-based secondary outcomes. It also lists 8 outcome measures and 22 analyses. The record does not report a prespecified hierarchy among outcomes, a multiplicity adjustment, or a complete analysis plan. Without that information, the role of each test in confirmatory inference is unclear. Multiple outcomes and comparisons increase the need to distinguish a primary question from exploratory follow-up analyses.

The global tests do not identify specific group pairs. The recalculated pairwise analyses are unadjusted, so their p-values do not account for testing multiple contrasts. They are best read as descriptive supplementary analyses rather than as definitive findings. The reported global p-values should also be interpreted in context: statistical evidence of across-group variation does not show that every pair differs or that an observed difference is clinically important.

The primary endpoint identifies the ITT population, but further details about the analysis population, missing data, and censoring are not reported in the registry record. The record does not describe how participants with no qualifying post-Day-28 testosterone value, incomplete follow-up, or unavailable laboratory measurements were handled. Nor does it report sensitivity analyses for missing measurements or alternative event definitions.

Safety denominators and numbers at risk are not reported in the registry record. As a result, the posted adverse-event counts cannot be converted into comparable group rates without making unsupported assumptions. Death counts are not reported in the safety summary. The absence of those details is an evidence-reporting limitation and should not be read as evidence that events did not occur.

The sample-size justification, interim analyses, and detailed randomization and allocation procedures are also not reported in the registry record. The available information supports a cautious description of the posted endpoints and tests, but not a full audit of the trial's planned inferential framework.

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

The primary endpoint indicates how long after one degarelix dose it took for a measured testosterone value to rise above 0.5 ng/mL under the stated definition. The reported medians differ across the eight groups, and the sponsor's global log-rank test reports evidence of an overall difference in time-to-event distributions. These findings describe the posted laboratory outcome in this study population and follow-up setting.

They do not establish that one regimen is superior to another in a clinically meaningful sense. The global test does not identify which groups differ, the group confidence intervals show uncertainty, and there is no non-degarelix comparator. The observed differences also cannot be attributed to dose alone when dose and concentration vary across regimens. No hazard ratios are reported for the primary result, and no dose-trend analysis is reported.

The endpoint is not a direct measure of tumor control, survival, symptoms, or quality of life. The registry describes pharmacokinetic, pharmacodynamic, and safety aims, but the primary result concerns a laboratory threshold. The secondary testosterone outcomes provide related information on the same biological measure; they do not by themselves establish a broader clinical outcome.

The posted safety counts are descriptive, and group denominators are missing from the safety summary. They therefore do not support reliable comparisons of adverse-event rates. Similarly, the small arm counts and broad intervals for some outcomes mean that the magnitude of group differences is uncertain. A non-significant pairwise result is not proof of no difference, and an unadjusted nominal p-value is not conclusive evidence when multiple comparisons may be relevant.

Overall, the registry record offers evidence that the measured testosterone time-to-event distributions varied across the studied regimens. It does not establish the best dose, comparative effectiveness against another treatment, or a definitive safety profile. Those questions require outcomes and analyses that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the distinction between a global comparison across multiple groups and the pairwise questions readers often want to ask. The sponsor's log-rank analysis tests for an overall difference in time-to-event experience. It does not name a winning dose or quantify a particular contrast. Group medians and confidence intervals help describe the pattern, but they cannot replace a specified pairwise analysis.

The endpoint also shows why the definition of an event matters. A single testosterone measurement greater than 0.5 ng/mL from Day 28 onwards defines the primary event, while the secondary outcomes use durations of testosterone at or below the threshold. These are related but distinct estimands. Clear operational definitions are essential for understanding what the statistical result represents and what it leaves out.

Concentration and dose vary across the eight regimens, so an apparent ordering of outcomes should not automatically be interpreted as a dose-response relation. A suitable model or planned trend analysis would be needed to answer that question, and such an analysis is not reported in the registry record. The case also emphasizes that secondary unadjusted comparisons are exploratory when multiplicity handling is not described.

Finally, sample-size planning illustrations based on observed effects are not a substitute for a trial's original design rationale. They can show how planning assumptions change with the effect targeted, but the registry record does not report the original justification. These distinctions help keep statistical evidence, uncertainty, and clinical interpretation separate.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record provides limited information for assessing how the study was conducted and analyzed. It identifies a randomized, open-label, parallel and sequential ascending design, but the exact randomization procedure, allocation concealment, and sequence details are not reported in the registry record. The absence of masking may be relevant to measurement and reporting, although the endpoint is a laboratory value; the record does not describe safeguards for measurement or assessment.

There is no placebo or different-treatment group listed. Comparisons among degarelix regimens cannot establish what would have occurred without degarelix or with another treatment. In addition, dose and concentration are not independently varied across every regimen, so the effect of either factor alone cannot be separated from the posted group summaries.

For the primary outcome, the record gives the event definition and ITT population but not details of censoring, missing testosterone measurements, follow-up completeness, or sensitivity analyses. The stated timeframe is 3 months, while the posted medians and confidence intervals extend across a range of days; the registry does not explain the precise follow-up and censoring conventions behind these estimates. The available summary is therefore insufficient to reproduce or fully evaluate the time-to-event analysis.

Arm sizes are modest, and several confidence intervals are broad. The record does not report a sample-size justification, a complete statistical analysis plan, or multiplicity handling. The posted secondary results cover only some listed outcomes. Safety counts lack denominators and numbers at risk, preventing rate-based comparisons. These limitations constrain the precision, reproducibility, and scope of conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigation of a New Trial Drug (FE200486) in Prostate Cancer Patients — NCT00818623.
• Registry record last updated 2023-11-30; status last verified 2011-05.
• Results first posted 2009-03-31.
• 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

NCT00818623 is a completed phase 2, randomized, open-label study of a single dose of degarelix (FE200486) in patients with prostate cancer. It enrolled 172 participants and compared eight dose and concentration regimens. The primary endpoint was median time from dosing until a testosterone value greater than 0.5 ng/mL, with results reported for the ITT population and a stated 3 months timeframe.

The sponsor reported a global log-rank p-value of < 0.001 across the primary endpoint groups. Two duration-based testosterone secondary outcomes have posted global Kruskal-Wallis tests. Pairwise secondary calculations are unadjusted and supplementary. The record does not report a placebo or active-treatment comparator, a complete analysis plan, multiplicity procedures, or detailed handling of missing measurements. Safety counts are posted without group denominators, limiting comparative interpretation.