Safety and Tolerability Study of MDV3100 in Combination With Docetaxel in Men With Advanced Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Study of MDV3100 in Combination With Docetaxel in Men With Advanced Prostate Cancer (NCT01565928), a na phase 1 study. The primary outcome is Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2.

2. Clinical Question

Statistically, the main question is descriptive: how often did dose reduction occur in the defined treatment periods? This is not a randomized efficacy comparison, and the record does not state a treatment-effect contrast against a control group. The study purpose in the brief summary is to determine safety. The listed secondary outcomes include vital-sign and electrocardiogram findings, as well as docetaxel pharmacokinetic measures with and without Enzalutamide treatment. Those listed outcomes provide context for the safety and drug-exposure questions, but the registry record does not report their numerical results in the registry record for this analysis.

3. Trial Design

The registry record describes a Phase 1b, open-label, safety and tolerability study of oral MDV3100 in combination with docetaxel in men with advanced prostate cancer. Its phase category is listed as Phase 1. Allocation is listed as not applicable, masking as none, and the study model as single group. The status is completed. Enrollment is listed as 23.

These design features matter when interpreting the reported groups. Open-label means the record does not describe masking of treatment assignment. A single-group study does not provide a randomized, concurrent control group for estimating a treatment contrast. The adverse-event listing includes a combination-treatment group and a post-docetaxel Enzalutamide group, but the record explicitly cautions that the arms are not a like-for-like control comparison. The groups should therefore be read in their stated treatment contexts, not treated as parallel randomized arms.

The title names MDV3100, while the intervention and outcome descriptions use Enzalutamide and Docetaxel wording. The combination group is labeled Docetaxel 75 mg/m^2 plus Enzalutamide 160 mg, and the other group is labeled Post-Docetaxel Enzalutamide 160 mg. The registry record does not explain this naming relationship further. No inference about the sequence, treatment duration beyond the stated primary-outcome timeframe, or protocol rationale should be drawn from the group labels alone.

The record lists a primary dose-reduction outcome and several secondary outcomes, including clinically significant vital-sign abnormalities, clinically significant ECG changes, and docetaxel maximum concentration and area-under-the-curve measures with and without Enzalutamide treatment. The full statistical plan, including planned estimands and methods for comparing pharmacokinetic measures, is 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all enrolled participants who received at least 1 dose or partial dose of study drug (Enzalutamide and/or Docetaxel).

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.

Population: Intent-to-treat (ITT) population included all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Required Study Drug Dose Reduction During Treatment Periods 1 and 2, measured over Treatment Period 1 (Day 1) up to end of Treatment Period 2 (42 days).

The primary endpoint is the percentage of participants who required study drug dose reduction during Treatment Period 1 and Treatment Period 2. The stated timeframe begins at Treatment Period 1, Day 1, and continues up to the end of Treatment Period 2 at 42 days. The endpoint description says it reports dose reductions of Docetaxel and Enzalutamide treatment. It also states that dose modifications could include interruptions or reductions when adverse events were intolerable or could not be improved by other means, with reductions or delays determined according to prescribing information and at the investigator’s discretion.

A percentage is a binary-outcome summary: each participant is classified according to whether the specified event occurred, then the event frequency is expressed relative to an eligible denominator. In general, this kind of measure can communicate how commonly treatment adjustment was needed in the defined population and period. Its interpretation depends on a clear event definition, an explicit denominator, and consistent handling of participants with incomplete follow-up.

The record defines the safety population as enrolled participants who received at least 1 dose or partial dose of study drug, Enzalutamide and/or Docetaxel. It does not provide the primary endpoint’s observed percentage, numerator, denominator, confidence interval, or missing-data handling in the registry record. Thus the endpoint’s clinical and statistical size cannot be assessed from the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

In general, a percentage for a binary event summarizes the fraction of an analysis population meeting a prespecified condition. Here, the condition is requiring a study drug dose reduction during the stated treatment periods. For a percentage to be interpretable, the event definition and the analysis denominator need to be clear. The registry record defines a safety population based on receipt of study drug, but the primary endpoint’s reported numerator and denominator are not included in the registry record. It is therefore not possible to reconstruct or verify the endpoint estimate.

Binary outcomes discard some detail about timing and duration. A participant either meets the endpoint definition or does not, even if dose modification occurs at different times or for different reasons. The outcome description gives a clinical context for dose modification, including adverse events that were intolerable or could not be improved by other means, and investigator discretion guided reductions or delays. The record does not state how interruptions, delays, or multiple dose changes were handled when deriving the primary percentage. In particular, its wording distinguishes the broader permission for modifications from the primary endpoint’s focus on dose reductions.

How should uncertainty be understood?

In general, a confidence interval describes the range of values compatible with an estimate under the assumptions of the statistical method. For a binary percentage, interval width depends on the amount of information and the observed event frequency. A point estimate alone can appear more definitive than the underlying data warrant; an interval helps show precision. The registry record does not report a confidence interval for the primary dose-reduction outcome or for the listed serious-event percentages in the registry record. No interval can be inferred from the group counts without knowing the exact endpoint definitions, analysis population, and calculation method.

Likewise, a p-value, when used, addresses how compatible data are with a specified null model. It does not measure the size or clinical importance of an effect, and it does not establish causation. The record’s analysis count is zero, and no primary-outcome hypothesis test is reported in the registry record. There is therefore no basis for describing the primary endpoint as statistically significant or nonsignificant.

Why does the design affect comparisons?

In general, random allocation helps make treatment groups comparable on average, supporting causal comparisons when other design and analysis assumptions are met. This record lists allocation as not applicable, masking as none, and a single-group model. Its adverse-event groups are explicitly not a like-for-like control comparison. One group is labeled as combination therapy with Docetaxel 75 mg/m^2 plus Enzalutamide 160 mg; the other is a post-docetaxel Enzalutamide 160 mg group. The labels imply different treatment contexts, so their event figures should be described separately rather than interpreted as an estimate of the effect of one regimen versus another.

Open-label conduct can also matter in general, especially for outcomes involving clinical decisions. Knowledge of treatment may influence care or event assessment, though the registry record does not establish that such influence occurred in this study. Dose reductions were determined according to prescribing information and at investigator discretion, making transparent reporting of the endpoint rules and analysis population particularly relevant. The record does not report additional safeguards or adjudication procedures.

What can pharmacokinetic measures add?

In general, maximum plasma concentration summarizes a peak measured concentration, while area under the concentration-time curve summarizes exposure over a specified time interval. The listed secondary outcomes include docetaxel Cmax, AUClast, and AUCinf with and without Enzalutamide treatment. These are drug-exposure measures rather than direct measures of clinical benefit. Their interpretation would depend on sampling schedules, assay procedures, pharmacokinetic methods, and the populations contributing measurements. Those details and the numerical results are not reported in the registry record, so no exposure comparison can be described.

Over-dispersion is a general concern when observed variability in data exceeds what a simple statistical model assumes. For example, a model that assumes a common event probability or a particular variance structure may understate uncertainty if participants differ more than expected. This concept can matter in clinical data, but the record does not report a model for the primary binary outcome or evidence of over-dispersion. It would be inappropriate to claim that a particular adjustment was used or needed for this study.

What do planning calculations mean?

In general, a sample-size calculation describes the amount of information a future study might require under stated assumptions about the target effect, significance level, allocation, and statistical method. Such a calculation is a planning illustration, not observed power and not evidence that a study achieved a particular level of certainty. The registry record does not report the trial’s own sample-size justification or statistical plan. No numerical planning result for this primary endpoint is included in the registry record, and no new planning figure can be derived without an observed effect and additional assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and multiple secondary outcomes, including vital-sign abnormalities, ECG changes, and docetaxel pharmacokinetic measures. It reports seven outcome measures, but no analysis entries are reported in the registry record. The registry record does not describe a multiplicity strategy, such as a hierarchy of tests or an adjustment for testing several outcomes. Without a stated analysis plan and outcome results, it is not possible to determine how any multiple-testing issue was handled. In general, examining many outcomes can increase the chance of finding an apparently unusual result by chance; the importance of that issue depends on the analysis plan and how results are interpreted.

Missing-data handling for the primary endpoint is not reported in the registry record. The safety population definition includes enrolled participants who received at least 1 dose or partial dose of study drug, but that definition alone does not specify what happened if dose-reduction status or follow-up information was unavailable. The record does not state whether participants with missing endpoint information were excluded, counted in a particular way, or addressed through sensitivity analyses.

The registry record also does not report whether analyses followed an intention-to-treat principle or another named approach. Its defined safety population is relevant to safety descriptions, but should not be assumed to be the analysis population for every outcome. The group-specific adverse-event denominators likewise do not establish the denominator used for the primary endpoint. These omissions limit evaluation of the endpoint’s completeness, the risk of bias due to missing observations, and the comparability of results across outcomes.

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: atrial fibrillation (14.3%), febrile neutropenia (13.6%), acute coronary syndrome (9.1%), atrial flutter (4.8%), cardiac failure acute (4.8%).

The serious-adverse-event listing gives separate participant counts for two treatment contexts. For Combination Therapy: Docetaxel 75 mg/m^2+ Enzalutamide 160 mg, the record lists 8 affected participants among 22 at risk. For Post-Docetaxel Enzalutamide 160 mg, it lists 7 affected participants among 21 at risk. These are group-specific summaries, not a randomized comparison. The record also lists other affected participants as 21 among 22 at risk for the combination group and 18 among 21 at risk for the post-docetaxel group. The registry entries do not define the precise classification rules for the “other” category.

Among the top serious-event terms listed are atrial fibrillation at 14.3%, febrile neutropenia at 13.6%, acute coronary syndrome at 9.1%, atrial flutter at 4.8%, cardiac failure acute at 4.8%, and cardiac failure congestive at 4.8%. These term percentages should be read as registry-listed event summaries, not as evidence of a difference between the treatment contexts. The record does not give term-specific participant counts or denominators in the registry record.

Serious adverse events are not the same endpoint as the primary dose-reduction outcome. The record gives no deaths value for these groups, and the primary outcome result is not reported in the registry record. These figures describe recorded safety events; they do not establish that a regimen caused an event or quantify a comparative risk.

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

The study addresses safety and tolerability of MDV3100 in combination with docetaxel in men with advanced prostate cancer. Its primary outcome is a practical treatment-management measure: the percentage of participants requiring a dose reduction during the specified treatment periods. The registry record also lists serious adverse events and secondary measures related to vital signs, ECG changes, and docetaxel exposure. Those descriptions identify what the study set out to assess, but they do not supply the primary endpoint estimate or the numerical results for the secondary outcomes in the registry record.

Accordingly, the posted information does not establish how often dose reductions occurred, how precisely that frequency was estimated, or whether any observed result met a statistical criterion. It also does not permit a comparison of treatment effects. The two safety groups are not a randomized, like-for-like control comparison, and the record lists a single-group model with allocation not applicable. Separate counts across different treatment contexts should not be interpreted as evidence that one context produces more or fewer events than the other.

General statistical interpretation distinguishes description from causal inference. A count or percentage can describe what was observed in a defined group. Estimating a causal treatment effect ordinarily requires a design and analysis that address how treatment groups differ, along with explicit methods and uncertainty estimates. Those comparative elements are not reported for this record. The listed adverse-event terms and counts therefore remain descriptive.

The record’s missing numerical primary outcome also means its precision cannot be judged. In general, uncertainty intervals help show how compatible an estimate is with a range of underlying values, while a clear denominator helps readers understand the population represented. Neither a primary outcome interval nor its numerator and denominator is present in the registry record. The result should not be treated as zero or as evidence of no dose reductions; it is simply not reported in the registry record.

The appropriate conclusion is bounded: the registry record documents a completed, open-label safety and tolerability study and defines its primary dose-reduction question, but the information is insufficient to quantify the primary finding or make a comparative treatment claim.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it illustrates how safety questions can be framed around treatment modification as well as adverse-event occurrence. A dose reduction is a clinically meaningful study outcome in the broad sense that it records a treatment adjustment, while serious-event summaries describe a separate aspect of safety. Keeping these outcomes distinct avoids treating a modification decision as equivalent to an adverse event or as a direct measure of drug exposure.

The design also highlights the limits of comparisons in nonrandomized records. The registry lists a single-group model and states that the displayed treatment contexts are not a like-for-like control comparison. This distinction is important when readers encounter separate event counts or percentages: a numerical difference between groups would not, by itself, show a treatment effect. Differences in treatment period and participant contribution may affect such summaries, and no comparative analysis is reported.

Another statistical lesson is the importance of complete outcome reporting. The primary outcome is carefully named and has a stated timeframe, but the registry entries do not include its estimate, denominator, or uncertainty. A precise outcome definition is necessary, but it is not enough to evaluate the observed result. Readers also need the numerical finding and a clear account of the analysis population and missing observations.

Finally, the record lists safety and pharmacokinetic questions together. In general, pharmacokinetic measurements characterize exposure, while clinical safety outcomes describe events or treatment changes. They answer related but distinct questions. The listed Cmax and area-under-the-curve measures should not be substituted for the primary dose-reduction outcome, and the record’s outcome descriptions alone do not establish how exposure related to safety.

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 main limitation for statistical interpretation is that the primary endpoint is described without a reported result in the registry record. Its numerator, denominator, percentage, and uncertainty are unavailable, so its magnitude and precision cannot be assessed. The record defines a safety population but does not state whether that same population was used for the primary endpoint.

The study is open-label, with allocation listed as not applicable and a single-group model. The adverse-event groups are explicitly not a like-for-like control comparison. Their counts should therefore remain descriptive and should not be interpreted as treatment contrasts. The different group labels also place the observations in different treatment contexts, including a post-docetaxel period.

The titles and group descriptions use MDV3100 and Enzalutamide wording, but the registry record does not explain their relationship in the registry record. This makes it important not to assume details beyond the labels. The full protocol, statistical analysis plan, dose-modification rules beyond the brief description, and analysis populations for secondary outcomes are not reported in the registry record.

Missing-data procedures and multiplicity handling are not reported. Nor are confidence intervals or inferential analyses for the primary outcome. The listed serious-event terms lack term-specific counts and denominators in the registry record. Finally, the enrollment figure and safety-group denominators do not establish a common endpoint denominator, and no total of unique participants across treatment contexts should be inferred from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability Study of MDV3100 in Combination With Docetaxel in Men With Advanced Prostate Cancer — NCT01565928.
• Registry record last updated 2019-04-22; status last verified 2019-01.
• Results first posted 2019-04-22.
• 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, open-label Phase 1b safety and tolerability study of oral MDV3100 with docetaxel in men with advanced prostate cancer. Its phase category is Phase 1, its model is single group, and allocation is listed as not applicable. Enrollment is 23.

The primary outcome is the percentage requiring dose reduction during Treatment Period 1, Day 1, through the end of Treatment Period 2 at 42 days. The outcome result is not reported in the registry record. The registry record defines a safety population based on receiving at least 1 dose or partial dose of study drug.

Serious adverse events are listed separately for combination therapy and a post-docetaxel Enzalutamide treatment context; the record cautions that the groups are not a like-for-like control comparison. Secondary outcomes include vital-sign and ECG findings and docetaxel pharmacokinetic measures. The statistical plan, missing-data methods, and multiplicity approach are not reported in the registry record.