Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486 (NCT00117949), a randomized phase 2 study. The primary outcome is Time to Meet Insufficient Testosterone Response.

2. Clinical Question

The registry record describes the study as randomized, open-label, multicenter, and parallel-group. Its stated purpose was to generate pharmacokinetic, pharmacodynamic, safety, and tolerance information to guide dose selection for Phase 3. The primary endpoint focuses on the timing of an insufficient testosterone response, rather than directly measuring all aspects of drug exposure, safety, or longer-term clinical outcomes.

3. Trial Design

This completed Phase 2 study is listed as randomized, open-label, multicenter, and parallel-group. Its official title describes an ascending single-dose study. The intervention groups received degarelix at 40 mg, 80 mg, 120 mg, or 160 mg. The registry record reports enrollment of 82 participants and lists prostate cancer as the condition under study. Ferring Pharmaceuticals is named as the sponsor.

The registry record gives a start date of 2002-04 and a primary completion date of 2004-01. Although the study is described as randomized, the method used to generate the allocation sequence, the allocation ratio, and procedures for concealing assignments are not reported in the registry record. Masking is listed as none, so the study was open-label. Details about how investigators or participants knew the assigned dose are not reported in the registry record.

The groups differed by assigned dose, rather than by use of different active treatments. The registry record does not list a placebo or an untreated comparison group. The reported primary comparison is across all four dose groups, while the posted secondary comparisons use the 40 mg group as a reference. Arm sizes were 10.0 participants for 40 mg and 24.0 participants in each of the other groups. The record does not explain why the arm sizes differed.

The stated purpose was to develop population pharmacokinetic and pharmacodynamic information and generate safety and tolerance data that could inform dose selection for Phase 3. The registry record does not report a sample-size justification, detailed eligibility criteria, treatment administration procedures, or a protocol-level account of planned analyses. Those omissions limit how fully the design and its intended operating characteristics can be evaluated.

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: Patients who withdrew without meeting the insufficient testosterone (T) suppression criteria were censored as of the time for last available T measurement prior to discontinuation. For the 40 mg group the 95% confidence interval around the time estimate was non-estimable and no statistical analysis is presented (the estimate was 14 days).

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 Time to Meet Insufficient Testosterone Response, measured over 3 months.

The primary endpoint is time to meet the study definition of an insufficient testosterone response, measured in days over a 3 months timeframe. The definition was testosterone >1.0 ng/mL at one visit, or testosterone from 0.5-1.0 ng/mL at two consecutive visits. The reported arm estimates are Kaplan-Meier estimates of the median time to that event.

A time-to-event endpoint captures both whether an event occurred and how long it took to occur. Kaplan-Meier estimation can account for participants whose event time is not observed during follow-up, rather than treating their last known observation as if it were the event time. In this study, participants who withdrew without meeting the insufficient testosterone criteria were censored at the time of their last available testosterone measurement before discontinuation.

The endpoint is used to describe the timing of the defined testosterone response, not to summarize every pharmacodynamic or clinical outcome. Its interpretation depends on the event definition, measurement schedule, follow-up, and censoring. The registry record does not report the visit schedule or further detail on follow-up after discontinuation. For the 40 mg group, the 95% confidence interval around the time estimate was non-estimable, and no statistical analysis was reported for that interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a Kaplan-Meier median describe?

In general, time-to-event methods estimate the distribution of time until a defined event. The Kaplan-Meier method incorporates information from participants whose event was not observed before follow-up ended or who were censored. A Kaplan-Meier median is the estimated time by which half of the event-time distribution has experienced the event, when that point can be estimated. It is not the arithmetic average event time.

For this study, the event was meeting the insufficient testosterone response definition. The endpoint therefore reflects time until that specific threshold-based event, not time to testosterone suppression, PSA reduction, a safety event, or another clinical outcome. The posted arm summaries are medians with full ranges. The full range reports the observed lower and upper event times; it is not a confidence interval for the median.

Why does censoring matter?

In general, censoring records that an event time is not fully observed while preserving information up to a participant's last observation. The analysis can use that participant's observed follow-up without assuming the event occurred at the censoring time. Censoring is not the same as counting an event, and it does not mean the participant had no event after leaving observation.

The registry record states that participants who withdrew without meeting the insufficient testosterone criteria were censored at their last available testosterone measurement before discontinuation. That is a specific censoring rule. The record does not report how many participants were censored, the reasons for withdrawal by arm, or whether additional censoring circumstances occurred. In general, interpretation of Kaplan-Meier estimates relies on assumptions about how censoring relates to the event process; the registry record does not report diagnostic checks for those assumptions.

What does the log-rank test assess?

In general, the log-rank test compares time-to-event distributions across groups while accounting for censoring. The registry record reports a log-rank test across the four dose groups and p < 0.001. This is an overall test: it assesses evidence of a difference somewhere among the group distributions, rather than specifying which pairs account for it. A p-value is not a measure of the size or clinical importance of a difference, and it does not show the probability that a hypothesis is true.

The registry record does not report pairwise primary tests, an effect estimate such as a hazard ratio, or a confidence interval for the overall comparison. It also does not report further details of the log-rank procedure. The reported p-value should therefore be interpreted within the scope of the stated overall comparison.

How should uncertainty be read?

In general, a confidence interval describes a range of estimates compatible with the data under a specified statistical procedure. It expresses uncertainty in an estimated quantity; it does not describe the full spread of individual observations. The sponsor reports 95% confidence intervals for the median times in the 80 mg, 120 mg, and 160 mg groups. For the 40 mg group, the interval around the time estimate was non-estimable, and no statistical analysis was reported for that interval. The record does not state why it could not be estimated.

The arm-level summaries include full ranges, which answer a different question from confidence intervals. A range can be broad even when an estimate is reasonably precise, or narrow when information is limited; uncertainty must be assessed using the appropriate inferential measure. Because the 40 mg confidence interval is not estimable, the precision of its median cannot be evaluated in the same way as the other sponsor-reported medians.

What do the secondary comparisons represent?

The posted secondary comparisons for the duration-of-suppression outcome include unadjusted risk differences against the 40 mg group. In general, a risk difference expresses the difference between two observed proportions. The accompanying confidence interval describes uncertainty in that estimate. An unadjusted p-value does not account for testing multiple outcomes or comparisons. These comparisons are exploratory unless a prespecified testing strategy establishes otherwise; such a strategy is not reported in the registry record.

For outcomes with counts, a denominator is needed to interpret how many participants experienced an outcome relative to the group at risk. The secondary outcome summaries report the arm sizes, counts, and some percentages, but the registry record does not describe missing observations or provide a fuller analysis-population account. Any recalculated comparison is an unadjusted calculation from posted summary statistics, not a substitute for an analysis based on participant-level data.

What can planning illustrations tell the reader?

In general, a sample-size calculation translates assumptions about an effect, variability, significance level, allocation, and desired power into a planning target. It is prospective planning, not evidence about the probability that a completed trial detected an effect. The planning illustrations associated with these results are based on the observed effect and stated assumptions, rather than the trial's own design. The registry record does not report its own sample-size justification. Such illustrations should not be interpreted as observed power or as evidence that the study was adequately sized for every outcome.

10. Analyses Reported by the Sponsor

The registry record reports the sponsor's overall primary comparison using a log-rank test across the four groups, with p < 0.001. It also reports sponsor median estimates and 95% confidence intervals for the 80 mg, 120 mg, and 160 mg groups. For the 40 mg group, the confidence interval was non-estimable and no statistical analysis was reported for that interval. These are the sponsor's reported analyses of the primary endpoint.

The posted arm summaries give medians of 77.0 days, 98.0 days, and 28.0 days for the 80 mg, 120 mg, and 160 mg groups, while the sponsor-reported medians are 84 days, 98 days, and 35 days. The registry record does not explain why these estimates differ for the 80 mg and 160 mg groups. The values should not be treated as interchangeable without knowing the estimation details. The record does not provide enough information to reconcile the differences.

The secondary comparisons include unadjusted recalculations based on posted summary statistics. They are not replacements for sponsor analyses, and the registry record does not report sponsor p-values for those comparisons. The reported overall primary log-rank result remains the sponsor's inferential comparison across the dose groups; the recalculated secondary results address different, more limited comparisons.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures and 24 analyses. It does not report a prespecified hierarchy of primary and secondary hypotheses, a family of tests for multiplicity control, or a correction method for multiple comparisons. The primary endpoint has an overall log-rank result across the four groups. The posted secondary comparisons include unadjusted p-values. Without a reported testing strategy, those secondary p-values do not establish confirmatory evidence across the collection of outcomes and comparisons.

Missing-data handling is described in part for the primary time-to-event endpoint: participants who withdrew without meeting the insufficient testosterone criteria were censored at their last available testosterone measurement before discontinuation. The number of withdrawals or censored participants, their distribution across groups, and the reasons for withdrawal are not reported in the registry record. The record does not report missing-data methods for the secondary outcomes or explain how incomplete measurements were handled.

The primary endpoint population is described in relation to this censoring rule, but a complete analysis-population definition is not reported in the registry record. The record does not state whether the primary analysis followed an intention-to-treat principle, how protocol deviations were treated, or which participants contributed to each secondary analysis. Those details matter because the analyzed participants and their available follow-up can affect estimated event times and outcome proportions.

The registry record does not report a sample-size justification, interim analyses, stopping rules, or the full statistical analysis plan. It also does not report whether outcomes, timepoints, or analyses were changed after study initiation. These omissions prevent a reader from assessing the planned power, the handling of multiple looks at accumulating data, or whether the reported analyses follow a prespecified plan. Absence of such information in the registry record is not evidence that a procedure was or was not used.

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

The primary result describes the timing of a defined testosterone response in four degarelix dose groups during the stated follow-up. The overall log-rank comparison indicates evidence of a difference among the time-to-event distributions under that test. The reported medians vary across groups, and they do not form a steadily increasing sequence with dose. These findings describe this study's endpoint and participants; they do not establish the cause of the observed pattern.

The endpoint is a laboratory-based threshold definition. It is not, by itself, a measure of symptom relief, quality of life, survival, or every aspect of prostate cancer control. The registry record lists other pharmacodynamic and safety outcomes, but results are not reported for all of them. The primary result therefore cannot answer questions about outcomes beyond the measures and follow-up that are reported.

The study is randomized, but open-label, and compares active dose groups without a placebo or untreated group. The overall comparison can describe differences between these dose groups; it does not estimate a contrast against no treatment. The available record does not include enough information about allocation procedures, participant characteristics, missing observations, or the full analysis plan to assess every potential source of bias or uncertainty.

The result should not be read as a claim that degarelix works or does not work. It is a statistical description of time to an endpoint under the study's definition, together with an overall test of differences among groups. The record's safety counts also require caution: denominators for participants at risk are not reported, and the record does not report deaths. Thus those entries cannot support a complete comparison of safety rates.

More generally, a statistically notable p-value does not establish clinical importance, prove a biological mechanism, or show that an observed pattern will be reproduced in another population. The registry record states that the studies were intended to help guide later dose selection, but it does not report a final dose-selection decision or later trial results.

13. Why This Trial Matters Statistically

This study illustrates why a multi-arm dose comparison is not always summarized by a simple monotone pattern. The primary medians differ across the four groups, but the highest listed dose does not have the longest median time to the defined event. An overall test can indicate differences among distributions without identifying the pairwise contrasts or explaining the shape of the pattern.

It also shows why estimands and summaries need to be kept distinct. A Kaplan-Meier median is a time-to-event summary that incorporates censoring, while a full range describes observed event times. Sponsor-reported confidence intervals add information about uncertainty, but an interval that cannot be estimated leaves a gap in precision assessment. The different median values in the posted arm summaries and sponsor-reported analyses for some groups further underline the importance of knowing estimation procedures before comparing summaries.

The broader lesson is that statistical interpretation depends on reporting beyond the headline test. Censoring rules, analysis populations, missing-data patterns, pairwise comparisons, and multiplicity plans shape what conclusions can reasonably be drawn. The registry record describes the primary censoring rule and overall test, but leaves many of these details unreported.

Finally, the study's stated aim was to produce pharmacokinetic, pharmacodynamic, safety, and tolerance information to guide dose selection. That purpose is different from establishing a definitive clinical outcome. Reading the endpoint in its design context helps distinguish an early dose-investigation result from evidence that would address broader treatment effects.

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 key limitation is incomplete reporting of the primary analysis details. The registry record gives an overall log-rank result and group summaries, but does not report pairwise primary comparisons, an overall effect estimate, or the full statistical analysis plan. It also does not explain why the 40 mg confidence interval was non-estimable or why some sponsor-reported medians differ from the posted arm summaries.

The record gives a censoring rule for withdrawals, but does not report the number of censored participants, their reasons for withdrawal, or censoring patterns by group. It does not report detailed visit timing or the completeness of testosterone measurements. These details would help readers assess how much follow-up informed the time-to-event estimates and how informative the censoring may have been.

Participant characteristics beyond the condition and enrollment are not reported in the registry record. Eligibility criteria, disease characteristics, and other factors that could affect the relevance of the findings are not described in the available record. The allocation sequence method and ratio are also not reported, despite randomization being listed.

Safety reporting is limited. The registry record lists counts affected by serious and other adverse events by group, but does not report participants at risk or deaths. It lists two serious adverse-event terms with percentages, but does not provide further details on event timing, severity, or attribution. Secondary outcome reporting is also incomplete, and a multiplicity strategy is not reported.

Finally, this is a single-dose, open-label study intended to inform dose selection. The registry record does not provide a sample-size justification, interim-analysis plan, or results for all listed outcomes. The findings should therefore be interpreted narrowly, with attention to the endpoint, reported follow-up, and limits of the registry information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Investigating the Pharmacokinetics, Pharmacodynamics and Safety of FE200486 — NCT00117949.
• Registry record last updated 2011-05-23; status last verified 2011-05.
• Results first posted 2009-06-05.
• 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

The registry record describes a completed, randomized, open-label, multicenter, parallel-group Phase 2 study of single-dose degarelix in patients with prostate cancer. It reports enrollment of 82 participants and four dose groups: 40 mg, 80 mg, 120 mg, and 160 mg. The stated aim was to generate pharmacokinetic, pharmacodynamic, safety, and tolerance information to guide dose selection for Phase 3.

The primary endpoint was time to an insufficient testosterone response during the 3 months timeframe. Kaplan-Meier medians and an overall log-rank comparison were reported. The overall test indicated a difference among group time-to-event distributions, while the medians did not follow a steadily increasing pattern with dose. Several analysis details, including the sample-size justification, full analysis plan, missing-data patterns, and multiplicity strategy, are not reported in the registry record. Secondary reporting is incomplete, and safety counts lack reported at-risk denominators.