Safety and Pharmacokinetics Study of ODM-201 in Castrate Resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Pharmacokinetics Study of ODM-201 in Castrate Resistant Prostate Cancer (NCT01317641), a randomized phase 1, phase 2 study. The primary outcome is Phase 1: Number of Participants Who Experienced Dose Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

The registry describes a Phase 1 and Phase 2 study of ODM-201 in patients with castrate resistant prostate cancer. Its official title characterizes the study as open, non-randomised, uncontrolled, multicentre, and using multiple dose escalation, with a randomised Phase II expansion component. The general design fields also describe allocation as randomized, masking as none, and a parallel model. These descriptions indicate different elements or stages of the design; further details reconciling them are not reported in the registry record.

The study status is completed. The registry lists a start of 2011-03, primary completion of 2013-07, and enrollment of 136. Phase 1 evaluated six dose levels, from 200 mg/Day through 1800 mg/Day. The primary endpoint is restricted to Phase 1 and reports the number of participants with dose-limiting toxicity. The Phase 2 adverse-event entries include 200mg/Day, 400mg/Day, and 1400mg/Day groups. Secondary PSA outcomes are reported by treatment-history subgroup and dose; group sizes differ across those outcomes.

Although a Phase II expansion is described as randomized, the registry record does not report the randomization procedure, allocation ratio, concealment method, or the detailed basis for the dose comparisons. Arm descriptions are blank. The study’s brief summary says its purpose was to evaluate safety, tolerability, and pharmacokinetics. Pharmacokinetic results are not included in the posted outcome details. A sample-size justification, protocol-specific analysis plan, and details of interim analyses are not reported in the registry record. Thus the design can be described at a broad level, but not reconstructed in full from the registry entries.

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.

Before assignment: 136 participants participated in the study, including 24 enrolled in Phase 1 and 112 in Phase 2 randomly assigned to 200 mg, 400 mg or 1400 mg daily doses and stratified by previous chemotherapy and treatment with CYP17 inhibitor. Two participants assigned to treatment did not start ODM-201, and were therefore excluded from analyses populations.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants in Phase 1 who received any 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

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1: Number of Participants Who Experienced Dose Limiting Toxicity (DLT), measured over Up to 28 days for each cohort.

The primary endpoint is the number of Phase 1 participants who experienced dose-limiting toxicity, with a timeframe of up to 28 days for each cohort. The registry defines a dose-limiting toxicity as any Grade 3 or more toxicity under National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, with specified exceptions. These exceptions include less than Grade 4 neutropenia or thrombocytopenia, hematological toxicity lasting less than 7 days, and nausea, vomiting, or diarrhea controlled with antiemetic and/or anti-diarrheal treatment.

This endpoint is used in dose escalation to describe whether serious toxicity meeting the protocol’s stated criteria occurred during the specified observation window. It is a count, not a measure of all adverse events, overall tolerability, or longer-term safety. A zero count for this endpoint does not mean that no adverse events occurred: the registry separately records other adverse events and serious adverse events across Phase 1 and Phase 2 groups.

The stated analysis population includes all Phase 1 participants who received any study drug. The posted primary results report zero participants with a dose-limiting toxicity in each of the six Phase 1 dose groups. The registry does not provide an interval estimate for these counts or a statistical comparison between dose levels. The primary endpoint should therefore be read as a descriptive safety finding within each listed cohort and within the defined observation period, rather than as evidence that the dose groups have equivalent risks.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a risk difference describe?

For a binary outcome, a risk difference compares the proportion with the outcome in one group with the proportion in a reference group. A positive value means the observed proportion was higher in the named group; a negative value means it was lower. This is a general statistical interpretation, not a claim about causation. In these registry comparisons, the outcome is a PSA decline of at least 50% by 3 months. The posted estimates compare selected ODM-201 dose groups with the 200mg/Day group.

For example, the chemotherapy-naïve and CYP17i-naïve comparison of 400mg/Day with 200mg/Day reports a risk difference of 0.192. Its interval runs from -0.186 to 0.570. Because the interval crosses zero, the posted summary is compatible with a difference in either direction as well as with little or no difference. The estimate alone does not communicate that uncertainty; it must be read alongside the interval and the group counts.

How should confidence intervals be read?

In general, a confidence interval conveys the precision of an estimate under the assumptions of the method used. A narrower interval indicates greater precision than a wider interval, while a wide interval signals that the data are compatible with a broad range of values. It does not assign a probability to the true effect being inside the particular interval. The registry does not identify the interval method for these comparisons, so its assumptions and performance cannot be checked from the record.

The intervals for the posted PSA risk differences include zero. This means the reported data do not distinguish the estimated contrast from no difference using that interval criterion. It does not establish that the groups are equivalent. Equivalence would require a prespecified margin and an analysis designed to assess it; these are not reported in the registry record.

What does an unadjusted p-value add?

In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The posted secondary comparisons give unadjusted p-values, including 0.327, 0.665, 0.087, and 0.309. The record does not report a statistical analysis plan explaining which contrasts were planned or how multiple comparisons were to be handled. These p-values therefore do not, on their own, support a confirmatory interpretation.

Why do group sizes matter?

In general, binary outcome estimates are less precise when based on fewer observations, particularly when outcome counts are small or absent. The PSA subgroup entries have differing denominators and event counts, and some dose groups contain very few participants. This variation makes direct visual comparison of the observed counts potentially misleading: groups with different denominators do not have directly comparable counts, and small groups can produce unstable proportions. The reported uncertainty intervals are important context for that reason.

What do the planning illustrations mean?

The registry’s planning illustration uses the observed effect as a basis for hypothetical future sample sizes. It states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with planning targets based on fractions of the observed effect. These figures are planning illustrations, not observed power and not the sample-size justification for this study. The justification for the actual study size is not reported in the registry record. Such illustrations also depend on whether the observed effect is a useful estimate for future planning, which is uncertain when the groups are small.

Why is the primary endpoint descriptive?

The primary endpoint is a count of participants meeting a defined toxicity criterion within each dose cohort. The record supplies the dose-specific counts but no inferential analysis or interval estimates for the DLT endpoint. General statistical reasoning cautions against interpreting zero observed events as proof of zero underlying risk, especially with limited cohort sizes and a specified observation window. Here, the relevant conclusion is limited to the posted counts and definitions; the registry does not provide enough information to quantify the uncertainty around a dose-specific underlying risk.

Finally, the registry lists no reported analyses. The comparison estimates and planning illustrations should not be mistaken for a fully documented sponsor analysis. The analysis methods, adjustment strategy, missing-data handling, and any sensitivity analyses are not reported in the registry record. This limits independent assessment of the assumptions behind the secondary comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a multiplicity strategy, or a hierarchy among the outcomes. It lists 17 outcome measures and 15 posted secondary outcomes, and the PSA entries include more than one dose comparison across more than one treatment-history subgroup. When many outcomes or contrasts are examined, some may appear notable by chance even if there is no underlying difference. This is a general statistical issue. Without a prespecified testing strategy or adjustment method, the unadjusted secondary p-values should be interpreted cautiously and should not be treated as definitive tests.

Missing-data handling is not reported in the registry record. The outcome entries give group-specific denominators, but the record does not explain whether participants without an assessment were excluded, classified in a particular way, or handled using another rule. It also does not report reasons for missing outcome measurements or sensitivity analyses assessing how missing observations could affect the results. The denominator for each posted result is therefore essential context, but it does not by itself explain how the analysis population was formed.

The primary endpoint population is defined as all Phase 1 participants who received any study drug. The registry does not provide equivalent analysis-population detail for the secondary PSA outcomes. It also does not report whether all participants were analysed according to assigned dose, whether dose changes were handled, or whether any outcomes were assessed by a different population definition. These details should not be inferred from the overall enrollment entry.

Finally, no reported analyses are listed. The methods used to produce inferential summaries, the treatment of protocol deviations, and any interim analyses are not reported in the registry record. These omissions restrict the ability to assess confirmatory intent, potential selection effects, and robustness of the posted secondary comparisons.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary retention (33.3%), hand fracture (25.0%), laceration (25.0%), muscle injury (25.0%), general physical health deterioration (14.3%).

The registry records serious adverse events and other adverse events separately from the primary DLT endpoint. For Phase 1, serious adverse events affected 0 of 4 participants at 200mg/Day, 2 of 7 at 400mg/Day, 0 of 3 at 600mg/Day, 1 of 4 at 1000mg/Day, 1 of 3 at 1400mg/Day, and 0 of 3 at 1800mg/Day. Other adverse events affected 4 of 4, 5 of 7, 2 of 3, 4 of 4, 3 of 3, and 2 of 3 participants, respectively, across those same Phase 1 doses.

For Phase 2, serious adverse events affected 2 of 38 participants at 200mg/Day, 3 of 37 at 400mg/Day, and 4 of 35 at 1400mg/Day. Other adverse events affected 33 of 38, 35 of 37, and 27 of 35 participants, respectively. These are descriptive participant counts; they do not establish that dose caused a difference. The record’s listed serious-event terms include urinary retention at 33.3%, hand fracture, laceration, and muscle injury at 25.0%, and general physical health deterioration and staphylococcal infection at 14.3%. The denominator and calculation basis for these term percentages are not reported in the registry record. Death counts are not reported in the registry record.

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

The primary result means that the registry reports no participants meeting its DLT definition in any listed Phase 1 dose cohort during follow-up of up to 28 days for each cohort. The definition includes toxicity grade and specified exceptions, so the result applies to that particular endpoint rather than to every possible safety event. The separate adverse-event entries make clear that other and serious events were recorded.

It does not mean that ODM-201 has no toxicity, that all doses have the same safety profile, or that longer-term risks are absent. The cohorts are small, and the registry does not provide uncertainty intervals for the primary counts. A zero observed count is not the same as proof that the underlying event risk is zero. The Phase 1 observations also should not be merged with the Phase 2 adverse-event entries, which represent different study components and populations.

The secondary PSA comparisons describe observed group differences, but their uncertainty intervals include zero and the record lists no reported analyses. These results do not establish that one dose is superior, that doses are equivalent, or that ODM-201 produces a clinically meaningful response. The registry does not report a confirmatory analysis plan, adjustment for multiple comparisons, or details of missing data for these outcomes.

More generally, a registry result is a record of specified outcome entries, not a complete account of every design and analysis decision. The record’s stated purpose includes safety, tolerability, and pharmacokinetics, but the entries do not provide a complete assessment of pharmacokinetics or all clinical outcomes. Interpretation should remain bounded by the endpoints, populations, and follow-up periods explicitly described.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and study phases matter when reading clinical statistics. The primary outcome is not an overall adverse-event rate; it is a count of participants who met a specific DLT definition during a limited observation window. The registry separately reports serious and other adverse events, which helps show why a zero primary count must not be translated into “no adverse events.”

The design also combines a Phase 1 multiple-dose escalation study with a randomized Phase II expansion component. That structure can produce different populations and different inferential questions within one registry record. The record describes the broad design but does not report enough detail to reconstruct the randomization procedures or explain exactly how the posted dose comparisons were generated. Recognizing this gap prevents overinterpretation of the label “randomized” as proof that every comparison is a randomized contrast.

The PSA results demonstrate the importance of reading effect estimates with their intervals, not relying on the direction of observed counts or a p-value alone. Subgroup denominators vary, and several estimates are imprecise. A planning illustration based on an observed effect can also look concrete while remaining conditional on assumptions; it is not evidence of the study’s actual power or original design rationale.

Finally, the record highlights the role of transparent statistical reporting. Prespecified outcomes, analysis populations, missing-data rules, and multiplicity methods are essential for distinguishing descriptive findings from confirmatory tests. Their absence does not erase the posted observations, but it limits what can responsibly be concluded from them.

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.

Several trial-specific limitations constrain interpretation. The primary DLT outcome is limited to Phase 1 and a timeframe of up to 28 days for each cohort. The registry does not provide longer-term DLT estimates or uncertainty intervals around the dose-specific counts. The number of participants in each Phase 1 dose cohort is small, so the absence of an observed DLT should not be read as a precise estimate of risk.

The record’s overall enrollment entry does not mean that every participant contributed to every endpoint. The listed safety and secondary outcome denominators differ by dose, phase, and subgroup. Arm descriptions are blank, and detailed information about eligibility, dose assignment, treatment duration, adherence, and follow-up is not reported in the registry record. The registry also does not reconcile the broad allocation field with the official title’s distinction between a non-randomised escalation component and a randomised Phase II expansion.

For the secondary outcomes, multiple subgroups and dose contrasts are posted, but prespecification, multiplicity handling, and the statistical analysis plan are not reported. No reported analyses are listed. The record does not explain missing observations or the analysis populations for these outcomes. The intervals and unadjusted p-values therefore warrant cautious descriptive interpretation, not confirmatory conclusions.

Serious and other adverse-event counts are available, but the registry record does not report death counts. It also does not provide the denominator or calculation basis for the listed serious-event term percentages. The posted material does not supply a complete assessment of pharmacokinetics despite the study’s stated purpose, and it does not establish longer-term safety or comparative effects against an external control.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Pharmacokinetics Study of ODM-201 in Castrate Resistant Prostate Cancer — NCT01317641.
• Registry record last updated 2017-03-29; status last verified 2017-02.
• Results first posted 2017-03-29.
• 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

NCT01317641 is a completed Phase 1 and Phase 2 study of ODM-201 in patients with castrate resistant prostate cancer. The registry lists enrollment of 136, a start of 2011-03, and primary completion of 2013-07. The official title describes an open, non-randomised, uncontrolled, multicentre multiple-dose escalation study with a randomised Phase II expansion component.

The primary Phase 1 endpoint counted participants with DLT during up to 28 days for each cohort. The posted result is zero in each of the six dose groups. Separate safety entries report serious and other adverse events in Phase 1 and Phase 2. Secondary PSA decline outcomes are reported at 3 months by treatment-history subgroup, with dose comparisons that have uncertainty intervals including zero. The registry lists no reported analyses; details of multiplicity handling, missing data, and the statistical analysis plan are not reported in the registry record.