A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer (NCT00510718), a registered phase 1 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs).

2. Clinical Question

This is a safety and pharmacokinetic study, not a registry-posted comparative efficacy trial. Its stated purpose was to examine MDV3100 through dose escalation in patients with castration-resistant prostate cancer. The brief summary says additional patients would be enrolled in expanded cohorts at doses determined to be tolerable. It also says that patients who tolerated the drug and did not progress would be allowed to continue to look for a PSA response. That description is not evidence that a particular dose was tolerable or that a PSA response occurred; those results are not reported in the registry record.

The central statistical question is descriptive: what numbers of participants in each listed dose group had treatment-emergent adverse events, and how many had serious events? Because there is no control arm, the results cannot establish how event occurrence compares with a different treatment or with no study drug. Nor do counts by dose alone show that differences between dose groups were caused by dose. The registry describes a dose-escalation study, but does not report the allocation process or enough detail to treat the groups as exchangeable comparison groups.

3. Trial Design

The registry describes a Phase 1, multi-center, open-label, dose-escalation study of MDV3100. It lists the study as completed, with start date 2007-07-23 and primary completion date 2008-12-08. Enrollment is listed as 140. These registry entries describe the study record; they do not provide a participant flow accounting for how many people entered each dose group or completed each period.

MDV3100 is the only intervention listed, and the arm description names MDV3100. The safety results are organized by dose: 30 mg/Day, 60 mg /Day, 150/160 mg/Day, 240 mg /Day, 360 mg /Day, 480 mg /Day, and 600 mg /Day. A further group is labeled 160 mg /Day: Long Term Dosing Period. The registry does not explain the precise dose-escalation sequence, the criteria used to advance doses, or how participants were assigned to dose groups; these details are not reported in the registry record.

Open-label means the record does not describe masking of treatment. No comparator group is listed, and the registry does not state an allocation method. Accordingly, the dose-group results should be read as descriptive safety summaries, rather than as results of randomized treatment comparisons. The long-term dosing period is also reported separately and should not be treated as a control group or as directly comparable with the other dose groups without further study details.

The primary outcome concerns participants with treatment-emergent adverse events and treatment-emergent serious adverse events, from baseline up to 30 days after the last dose of study treatment. The timeframe is described as approximately maximum of 129 months. The listed secondary outcomes focus on MDV3100 pharmacokinetics after a single dose, including measures of plasma concentration over time, maximum concentration, time to maximum concentration, elimination half-life, apparent distribution volume, and apparent clearance. The registry lists 17 outcome measures overall, but the results do not include inferential analysis records.

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.

Single Dose Period: 1 Week

Multiple Dose Period: 12 Weeks

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 of study drug.

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: Safety population included all enrolled participants who received at least 1 dose of study drug.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs), measured over Baseline up to 30 days after last dose of study treatment (approximately maximum of 129 months).

The primary endpoint counts participants with treatment-emergent adverse events and treatment-emergent serious adverse events. The registry defines an adverse event as an untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship was considered possible. A treatment-emergent event is one that emerged during treatment and was absent beforehand, or that worsened during treatment relative to the pretreatment state.

The serious category is based on the event’s consequences or significance. The registry definition includes death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, or another event deemed significant. The record states that adverse events include both serious and non-serious events. A participant may therefore be represented in the serious-event count and in the count for other adverse events; these categories should not be added together as though they were necessarily distinct people.

Counting participants is a useful descriptive safety measure in an early-phase dose-escalation study: it records how many people experienced an event in each dose group during the stated observation window. It does not, by itself, describe event severity beyond the serious-event classification, the number of recurrent events, timing, duration, or whether investigators considered an event related to the drug. Those details are not reported in the registry record. The endpoint also does not measure a treatment benefit. The listed pharmacokinetic outcomes address drug exposure and disposition, while the primary endpoint is a safety count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted safety information is best understood as descriptive counting. For each dose group, it reports how many participants were at risk for the endpoint and how many had an event. A count answers how many participants were recorded with an event; it does not summarize how often events recurred in the same participant. The registry’s stated endpoint is a participant count, and its definition includes serious and non-serious adverse events.

What does a participant count convey?

A participant count provides an intuitive summary of whether any participants in a group had an event during the defined observation period. The group-specific counts shown on the page should be read with their group sizes in view. Small groups can be especially sensitive to the outcome of an individual participant, so a count from a small group should not be treated as a precise estimate of the experience that would be expected in a wider population. This is a general statistical consideration, not a claim that the registry’s counts are inaccurate.

Counts alone do not show the number of event episodes, their timing, duration, intensity, or clinical course. They also do not tell us whether an event was judged related to study drug: the registry definition explicitly includes events without regard to a possible causal relationship. Additional detail about event-level data, attribution, and follow-up by participant is not reported in the registry record.

Why do the dose groups not form a treatment comparison?

A randomized comparison uses an allocation process to support a balanced comparison between treatment groups. This record is open-label, lists no comparator arm, and does not state an allocation method. The dose cohorts therefore cannot be interpreted as randomized arms. In a dose-escalation study, groups may have been enrolled at different points in study conduct or may have had different exposure periods; the exact process is not reported in the registry record. This means that an apparent difference in event counts does not isolate the effect of dose.

Open-label conduct also means that treatment masking is absent. For outcomes involving clinical judgment, knowledge of treatment may affect reporting or assessment. This is a general concern with unmasked studies, not evidence that any specific event was misclassified in this study. The record does not describe event adjudication or independent review.

What would an inferential analysis add?

In general, an inferential estimate can quantify uncertainty about an event frequency or a contrast between groups. A confidence interval is a range of values compatible with the observed data under a stated statistical model; it conveys uncertainty rather than guaranteeing that the true value lies inside the interval. A hypothesis test can assess how incompatible the data are with a specified null hypothesis, but interpretation depends on the design, assumptions, and analysis plan. No such statistical analyses are listed in the registry record for these results, so there are no posted confidence intervals or tests to interpret.

Even if a comparison were calculated from summary counts, it would be an unadjusted re-calculation rather than the sponsor’s own analysis. A calculated contrast would not overcome the absence of a control group or unreported allocation details. It would also not answer whether groups differed in participant mix, exposure time, or follow-up. No recalculated comparison is necessary to read the posted counts descriptively.

How should the planning illustration be read?

The sample-size material elsewhere on the page is a planning illustration, not a report of observed power. It uses the observed effect as a planning reference, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a fraction of the observed effect. These assumptions define a hypothetical calculation; they are not evidence that the original study used the same assumptions. The sample-size justification and statistical design plan for the trial are not reported in the registry record.

General power calculations estimate how often a planned analysis would meet a specified decision rule under assumed conditions. They do not show that a completed study had a particular probability of finding a result, and they do not establish a treatment effect. The planning outputs should be treated as illustrations only. In this case, the underlying study is described as dose escalation without a listed control group, so assumptions involving equal allocation between two arms do not convert its safety cohorts into a randomized two-arm comparison.

Why can over-dispersion matter in other analyses?

In general, a count model may assume a particular relationship between the average event count and its variability. Over-dispersion means the observed variability exceeds what that model assumes. If ignored, standard errors and confidence intervals can be too optimistic. That concept is relevant when analyzing recurrent event counts or count outcomes, but this registry endpoint is framed as the number of participants with events, not the total count of repeated events. The posted information does not provide recurrent event data or a model, so no over-dispersion assessment is reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("MDV3100 (Enzalutamide) 30 mg/Day", "MDV3100 (Enzalutamide) 60 mg /Day", "MDV3100 (Enzalutamide) 150/160 mg/Day", "MDV3100 (Enzalutamide) 240 mg /Day", "MDV3100 (Enzalutamide) 360 mg /Day", "MDV3100 (Enzalutamide) 480 mg /Day")
n      <- c(3, 27, 28, 29, 28, 22)
events <- c(0, 6, 14, 8, 6, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  MDV3100 (Enzalutamide) 30 mg/Day  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  MDV3100 (Enzalutamide) 60 mg /Day  27  6  22.2  8.6  42.3  10.6  40.8  10.7  41.0
ARM  MDV3100 (Enzalutamide) 150/160 mg/Day  28  14  50.0  30.6  69.4  32.6  67.4  32.5  67.5
ARM  MDV3100 (Enzalutamide) 240 mg /Day  29  8  27.6  12.7  47.2  14.7  45.7  14.7  45.9
ARM  MDV3100 (Enzalutamide) 360 mg /Day  28  6  21.4  8.3  41.0  10.2  39.5  10.3  39.7
ARM  MDV3100 (Enzalutamide) 480 mg /Day  22  1  4.5  0.1  22.8  0.8  21.8  1.1  21.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary safety endpoint and multiple pharmacokinetic outcomes. Looking at many outcomes can raise a multiplicity issue: as a general statistical matter, the chance of at least one apparently noteworthy result can increase when many hypotheses are tested. Whether and how to address that issue depends on the prespecified analysis plan and the purpose of each outcome. The registry record does not report a multiplicity strategy, an inferential testing hierarchy, or an analysis plan. It also lists no statistical analyses, so no multiplicity adjustment can be assessed from the posted results.

The record defines a safety population as all enrolled participants who received at least 1 dose of study drug. This identifies the intended population for the safety endpoint, but the registry does not provide a fuller participant disposition or explain whether anyone was excluded from particular summaries. The number of people contributing to each dose-group safety result is visible in the posted counts, but reasons for missing observations or departures from follow-up are not reported in the registry record.

Handling of missing data is not reported in the registry record. The record does not say how incomplete adverse-event reporting, withdrawals, or missing outcome information were treated, or whether any sensitivity analyses were performed. These omissions matter because descriptive counts depend on what was observed and on the population included in each summary. The stated observation window runs from baseline up to 30 days after the last dose, with an approximately maximum of 129 months; the practical follow-up achieved for each participant is not reported.

The registry’s primary endpoint separates serious adverse events from other adverse events, while its definition says adverse events include both. The record does not describe a statistical method for handling participants who experienced events in both categories. The counts should therefore be read as separate descriptive summaries, not combined into a single count of unique participants.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (33.3%), confusional state (33.3%), myocardial infarction (11.1%), pneumonia (11.1%), spinal cord compression (11.1%).

Read each serious adverse-event result as the number of participants with at least one serious event among the number at risk in that dose group. The posted figures are 0 of 3 at 30 mg/Day; 6 of 27 at 60 mg /Day; 14 of 28 at 150/160 mg/Day; 8 of 29 at 240 mg /Day; 6 of 28 at 360 mg /Day; 1 of 22 at 480 mg /Day; and 1 of 3 at 600 mg /Day. For the 160 mg /Day long-term dosing period, the count is 10 of 18. These figures are participant counts, not event totals.

The seriousness definition includes events meeting specified consequences, such as hospitalization or a life-threatening experience, as well as events judged significant for another reason. Serious-event categories do not establish that the study drug caused the event. The registry definition applies regardless of whether a causal relationship was considered possible.

The listed serious-event terms include Convulsion, Confusional state, Myocardial infarction, Pneumonia, Spinal cord compression, and Pulmonary embolism, with percentages shown in the posted results. The registry record does not give enough context to assign those percentages to a dose group or interpret them as risks. Death counts by dose are not reported in the registry record.

Because the groups are not a like-for-like control comparison, do not compare these counts as though dose were the only difference between groups. Group sizes and exposure periods differ, and information needed to adjust or contextualize the counts is not reported.

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

The posted data describe adverse events recorded among participants in a Phase 1, open-label dose-escalation study of MDV3100. They show that participants in each listed dose group were observed for safety and provide counts for those with serious and other adverse events. The serious-event counts vary across groups, and the registry additionally lists several serious-event terms. These are descriptive findings from the study record.

They do not establish that MDV3100 caused any individual event. The endpoint definition explicitly includes events without regard to possible causal relationship. Nor do the counts estimate what would have happened to the same participants without study drug or with another treatment, because no comparator is listed. The record’s open-label design and unspecified allocation method further limit interpretation of between-group differences.

The counts also do not answer whether adverse events were more or less common at one dose than another in a causal sense. The dose groups are not described as randomized comparison arms, and the long-term dosing period is reported separately. The registry does not report participant-level characteristics, detailed exposure duration by group, event recurrence, adjudication procedures, or inferential analyses that might help evaluate differences. Consequently, the posted data should not be converted into a claim that one dose is safer than another.

The registry describes an aim to assess safety and pharmacokinetics, and mentions that some participants could continue to look for a PSA response if they tolerated treatment and did not progress. That statement about the study plan does not show that a PSA response occurred. Efficacy results and conclusions about disease control are not reported in the registry record.

Finally, sample-size calculations displayed elsewhere on the page are planning illustrations, not evidence of observed power or proof of efficacy. The registry does not report the trial’s sample-size justification or statistical analysis plan. The most defensible reading is therefore bounded: these are posted safety counts from a dose-escalation study, without a control-based estimate of treatment effect or a reported inferential analysis.

14. Why This Trial Matters Statistically

This trial is statistically useful as an example of how study design shapes the questions that results can answer. Its Phase 1, open-label, dose-escalation structure focuses attention on safety observation and pharmacokinetic characterization across dose groups. The primary endpoint is a participant count, and the record presents the safety information by dose and by a separate long-term dosing period.

The same structure also places clear limits on inference. An array of dose groups can look like a dose-response comparison, but without a comparator and a stated allocation method, differences in counts cannot be attributed to dose alone. This is an important distinction between describing observed group experience and estimating a causal effect. The group-specific counts are useful to report, but they do not substitute for a randomized comparison or a prespecified model.

The case also illustrates why outcome definitions matter. Treatment-emergent events are defined relative to the pretreatment state and treatment period, while serious events are classified by consequence or significance. These definitions determine what enters a count. The registry says events are counted without regard to possible causal relationship, so the safety summary should not be mistaken for an attribution analysis.

Finally, the record demonstrates the value of reporting analysis details. It lists outcomes and a safety population, but no statistical analyses, missing-data methods, or multiplicity strategy. Readers can describe the posted counts, yet cannot evaluate model-based uncertainty or a formal comparison. Planning illustrations on the page can teach how assumed effects and allocation affect sample-size requirements, but they remain separate from the design and analysis documented for this study.

15. Limitations

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

The registry record describes the trial as open-label and lists no comparator. Allocation is not stated, so dose groups cannot be treated as randomized arms. This limits causal interpretation of differences in adverse-event counts and prevents a controlled estimate of treatment effect. The registry also does not report the dose-escalation rules or explain how participants entered each cohort.

Although enrollment is listed as 140, the record does not provide a participant-flow account. The safety endpoint applies to enrolled participants who received at least 1 dose, but the record does not explain exclusions, discontinuations, or missing event observations by group. The actual follow-up time for individual participants is not reported, beyond the stated observation window and its approximately maximum of 129 months.

The posted results count participants with events, not the total number of event episodes. Event timing, recurrence, duration, severity detail beyond the serious classification, and attribution to study drug are not reported. Death counts by dose are not reported in the registry record. The listed percentages for serious-event terms are not accompanied by enough denominator or group context to interpret them as dose-specific risks.

No statistical analyses are listed. Confidence intervals, hypothesis tests, adjusted comparisons, the multiplicity approach, and missing-data handling are not reported in the registry record. The trial’s sample-size justification is also not reported, so the planning illustration should not be mistaken for the study’s original design rationale. The brief summary mentions looking for a PSA response in some participants, but efficacy results are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 1 Study of MDV3100 in Patients With Castration-Resistant (Hormone-Refractory) Prostate Cancer — NCT00510718.
• Registry record last updated 2019-10-03; status last verified 2019-09.
• Results first posted 2019-10-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed Phase 1, multi-center, open-label, dose-escalation safety and pharmacokinetic study of MDV3100 in patients with castration-resistant prostate cancer. It lists enrollment of 140, start date 2007-07-23, and primary completion date 2008-12-08. The intervention is MDV3100, and no comparator group is listed.

The primary endpoint counts participants with treatment-emergent adverse events and serious adverse events from baseline up to 30 days after the last dose. The registry defines a safety population as enrolled participants who received at least 1 dose. Posted safety results are arranged by dose group, with a separate long-term dosing period. Secondary outcomes include single-dose pharmacokinetic measures.

The record lists 17 outcome measures and no statistical analyses. It does not report the trial’s sample-size justification, missing-data methods, multiplicity approach, or a comparative efficacy analysis. The posted adverse-event counts are descriptive and should be interpreted within the limits of an open-label dose-escalation study without a listed control group.