Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors (NCT04525131), a na phase 2 study. The primary outcome is Number of Participants With Any Serious Adverse Events (SAEs).

2. Clinical Question

The study is described as a window-of-opportunity phase II study intended to characterize safety, dose tolerance, pharmacokinetics, and pharmacodynamics of CPX-POM at the recommended Phase 2 dose. Its registered primary outcome is specifically a count of participants with any serious adverse event, assessed using CTCAE version 5.0. That makes the primary question a descriptive safety question, not a comparison of CPX-POM with another treatment or with no treatment.

The registry record reports 1 participant with a serious adverse event among 12 participants at risk. It also lists 9 participants with other adverse events among 12 at risk, and no deaths. These figures describe events recorded in this study; they do not establish what would have occurred under a different treatment. The record does not report a control group, a treatment-effect estimate, or an efficacy outcome that would answer whether CPX-POM changes tumor outcomes.

3. Trial Design

NCT04525131 is recorded as a phase II, single-group, open-label study sponsored by CicloMed LLC. The registry describes it as a single-center study. It enrolled 12 participants with newly diagnosed or recurrent bladder tumors. The registered intervention was CPX-POM, a drug administered intravenously over 20 minutes once per day.

The study began on 2020-11-25, reached primary completion on 2022-12-30, and is listed as completed. These registry dates describe the study record; they do not provide information about each participant’s treatment dates or follow-up. The primary outcome timeframe is 35 days, but the timing of dosing relative to that outcome window and the duration of treatment are not reported in the registry record.

Because the design is single group, there is no concurrent control arm and no randomized allocation. The registry records masking as none, so the study is open label. In this design, outcome counts describe the participants observed while receiving the intervention. Without a comparison group, differences from an alternative treatment or from an untreated course cannot be estimated within the study.

The study’s stated purpose was to characterize safety, dose tolerance, pharmacokinetics, and pharmacodynamics at the recommended Phase 2 dose. The registered primary endpoint concerns serious adverse events. Treatment-related adverse events are listed as a secondary outcome, while the registry record does not give results for that secondary outcome in the information available. Details of dose escalation, dose-limiting toxicity rules, pharmacokinetic sampling, pharmacodynamic assays, or a statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Any Serious Adverse Events (SAEs), measured over 35 days.

The primary endpoint is the number of participants with any serious adverse event among people in the safety population receiving CPX-POM. It is recorded as a participant count, with a 35-day timeframe. The description says serious adverse events were assessed using CTCAE version 5.0. The posted results report 1 participant with a serious adverse event among 12 at risk.

A count of participants with at least one serious event is a useful descriptive safety measure because it summarizes how many people experienced an event meeting the serious-event definition during the stated observation period. It is distinct from a count of all events: one participant can experience more than one event, but the endpoint as titled counts participants, not the total number of event episodes. The registry does not give event-level detail sufficient to determine the number, timing, duration, or outcome of each serious event.

Seriousness and severity are not interchangeable concepts. A serious adverse event is classified using seriousness criteria, while CTCAE provides a framework for grading adverse-event severity. The record identifies CTCAE version 5.0 in the endpoint description, but it does not give individual grades or further operational details about event classification. This endpoint is intended to characterize safety during the specified period; by itself, it does not measure antitumor activity or establish that an event was caused by the study drug.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the posted safety result can and cannot establish. The registry outcome is a participant count: it records how many people had at least one serious adverse event, rather than how many event episodes occurred. A participant-level count avoids treating multiple events in one person as if they came from different people. It does not, however, describe the number or pattern of events experienced by each participant.

What does a count communicate?

A count is direct and easy to interpret in a small safety study. Here, the registry reports 1 participant with a serious adverse event among 12 participants at risk. The count refers to the stated safety population and 35-day timeframe. It is not a rate per person-time, because the registry record does not provide person-time or a rate calculation. Nor is it a comparison between treatment groups: the study has one group only.

When event counts are small, each participant’s outcome has substantial influence on the overall description. A count can identify that an event was observed, but it does not by itself estimate how frequently a similar event would occur in a broader population with high precision. Confidence intervals are one general way to express uncertainty around an estimate. No confidence interval is reported in the registry record for this outcome, so the posted count should be interpreted as a finite study observation rather than a precise population estimate.

Why does the design matter for interpretation?

Randomized comparison, when used, can support a more direct estimate of differences between assigned treatments by balancing factors across groups on average. That general principle does not apply as a within-study treatment contrast: the registry records a single group, no allocation, and no masking. As a result, there is no internal control for the event count. Observing an event after treatment does not alone establish that treatment caused it, and observing no deaths in the enrolled group does not establish that the risk of death is absent.

Open-label means masking was not used. This can matter for outcomes involving clinical assessment, reporting, or decisions about whether an event occurred or should be classified in a particular way. The registry specifies CTCAE version 5.0 for assessment of serious adverse events, but does not describe adjudication procedures, assessor roles, or any safeguards against assessment bias. Those details are not reported in the registry record.

How should a planning calculation be read?

A sample-size calculation can estimate how many participants a future study might require under stated assumptions. The registry’s planning illustration is based on the observed effect and specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it uses participants per arm.

Those assumptions do not describe the design registered for this study, which is single group and has no randomized comparator. The illustration is a planning aid, not an account of the study’s actual recruitment plan, and not observed power. A planning result based on an effect estimated from a small study can be unstable: the estimated effect may vary substantially from one sample to another. The registry record does not report a sample-size justification for the trial itself, and the numerical planning outputs are not part of the registry entries considered in this explanation.

What is not available for statistical assessment?

The registry lists no analyses. It does not report a statistical analysis plan, a model for the primary outcome, a hypothesis test, a p-value, or an interval estimate. Consequently, there is no basis in the record to describe adjustment for covariates, a prespecified estimation approach, or a formal test of a treatment difference. The endpoint is a count and the design is descriptive; no inferential comparison should be imputed where none is recorded.

Over-dispersion is a general issue in count data when variability exceeds what a chosen count model expects. It can affect standard errors and interval estimates when a count model is used. The primary endpoint is a count of participants with any event, which is also naturally expressed as a binary status for each participant. The registry does not report a count-model analysis, so over-dispersion is not a reported feature of the study’s analysis. More broadly, without a stated model and sufficient detail about participant-level observations, model-based assumptions cannot be checked from the registry summary alone.

The main statistical message is therefore descriptive: a specified number of participants in the safety population experienced the registered outcome during its stated timeframe. The design and reporting do not support a controlled estimate of comparative safety or an efficacy conclusion.

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("CPX-POM")
n      <- c(12)
events <- c(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  CPX-POM  12  1  8.3  0.2  38.5  1.5  35.4  1.9  36.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies serious adverse events as the primary outcome. It also lists incidence of treatment-related adverse events as a secondary outcome. The available record does not describe how the outcomes were prioritized beyond the primary designation, how multiple statistical tests were handled, or whether any multiplicity adjustment was planned. A multiplicity strategy is not reported in the registry record.

Multiplicity matters when several outcomes or analyses are tested. In general, conducting many tests can increase the chance that at least one result appears notable by chance, depending on the testing strategy. That concern cannot be quantified from the registry information because no analysis results, testing procedures, or multiplicity adjustments are listed. The number of outcome measures alone does not show that formal hypothesis tests were performed.

Missing-data handling is also not reported in the registry record. The primary result identifies 12 participants at risk, but the record does not describe whether any observations were missing, how incomplete follow-up was treated, or whether participants who stopped treatment remained under safety observation. It also does not provide a participant flow account or reasons for withdrawal. The posted result should therefore be read alongside this lack of information about follow-up completeness.

The primary outcome names the safety population, but the criteria defining that population are not reported in the registry record. An intention-to-treat population, per-protocol population, and detailed analysis-population rules are not reported. Without those definitions, the relationship between enrollment, treatment exposure, and the analyzed safety group cannot be assessed beyond the reported count of 12 at risk.

The registry record lists no analyses. It does not state whether an interim analysis was planned or conducted; that information is not reported in the registry record. These omissions limit assessment of the analysis process, but they do not alter the descriptive meaning of the posted participant count.

12. Safety Results

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

Deaths

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: hypoxia (8.3%).

The safety outcome reports 1 participant with any serious adverse event among 12 participants at risk during 35 days. This is a count of participants, not a count of every serious-event episode. The registry lists Hypoxia as the top serious-event term, at 8.3%, but does not provide a complete serious-event listing or further participant-level detail. It also reports 9 participants with other adverse events among 12 at risk and 0 deaths.

The serious and other adverse-event entries should be read as distinct summaries. The registry does not say whether the participants in those categories overlap, so their counts should not be added. The record identifies treatment-related adverse events as a secondary outcome but does not report that outcome’s results in the information available. The serious-event count therefore does not indicate how many events were considered treatment-related.

Seriousness does not necessarily mean a particular severity grade. The primary outcome description says events were assessed using CTCAE version 5.0, but the registry does not report individual grades, onset, duration, resolution, or event attribution. As with any single-group safety summary, the observation of an event does not by itself establish that CPX-POM caused it. The 35-day outcome window also should not be interpreted as evidence about safety outside that period.

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

The result establishes what was recorded for the registered primary safety outcome in this study: 1 participant in the safety population had any serious adverse event among 12 at risk during the 35-day timeframe. It also establishes that the adverse-event record lists 9 participants with other adverse events among 12 at risk, Hypoxia as the top serious-event term at 8.3%, and 0 deaths. These are descriptive observations from a phase II single-group study.

The result does not establish a causal link between CPX-POM and an adverse event. There is no comparator group, and the study is open label. Without a concurrent comparison, the registry result cannot estimate how event occurrence would differ under another intervention or under no study treatment. The result also does not establish an event rate beyond the registered observation period or a precise risk for a wider patient population.

The outcome is not an efficacy measure. Although the study’s stated aims include pharmacokinetics and pharmacodynamics as well as safety and dose tolerance, results for tumor response or other clinical benefit are not reported in the registry record. It would therefore be inappropriate to infer an effect on bladder tumors from the adverse-event counts.

The registry record does not give confidence intervals, p-values, or a detailed statistical analysis plan for the primary outcome. The result should not be treated as evidence of statistical significance or as proof that serious events are either common or rare beyond this enrolled group. Small safety studies can describe events and identify issues for further study, while leaving considerable uncertainty about frequency and causation.

In short, the posted data document a serious adverse event in the study population and provide several additional safety counts. Their scope is limited to the participants, outcome definitions, and timeframe recorded. They do not support a controlled comparison, a causal safety estimate, or a conclusion about treatment efficacy.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how study design defines the questions that results can answer. Its single-group, open-label structure is suited to describing observations among participants who received CPX-POM, but it does not create a randomized treatment contrast. Recognizing that distinction helps prevent a descriptive safety count from being read as a comparative effect.

The primary outcome is a participant-level serious-adverse-event count, which is useful for a focused safety description. Reporting the number at risk alongside the number with an event gives essential context. The record also distinguishes serious events from other adverse events and lists deaths separately. Those measures have different meanings and should not be combined without participant-level definitions or a prespecified summary rule.

The trial also illustrates the importance of matching sample-size calculations to the design. The registry’s planning illustration assumes equal allocation between two arms, while the registered study is a single-group trial. That illustration may help with future planning under its stated assumptions, but it does not describe the study’s actual design or demonstrate observed power. The trial’s own sample-size justification is not reported in the registry record.

Finally, reporting completeness matters to statistical interpretation. The registry identifies the safety population and a 35-day timeframe, but does not report missing-data procedures, detailed analysis methods, or results for all stated study aims. These gaps limit precision and reproducibility. The appropriate contribution of the posted result is therefore a bounded descriptive account, rather than a claim about comparative treatment effects.

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 main trial-specific limitation is the absence of a comparator. The registry records a single group with no allocation and no masking. This design cannot separate treatment-associated events from events that might have occurred because of the underlying condition, other care, or other factors. It also does not support a within-trial estimate of comparative safety or efficacy.

Enrollment was 12, and the primary result is based on the safety population. The small enrolled group limits how precisely the observed count can characterize event occurrence beyond these participants. The registry does not report a confidence interval or other uncertainty interval for the endpoint, so a quantitative precision assessment is unavailable.

The endpoint covers 35 days. The registry does not report the duration of treatment, participant-specific follow-up, or whether safety observation continued after treatment ended. The result therefore does not characterize events outside the registered timeframe. The record also does not provide event-level descriptions, individual severity grades, timing, duration, outcomes, or attribution for each event.

Several analysis details are not reported in the registry record: the definition of the safety population, missing-data handling, statistical methods, multiplicity strategy, and any interim analysis. The results of the secondary outcome on treatment-related adverse events and of the stated pharmacokinetic and pharmacodynamic aims are also not reported in the registry record. These limits restrict evaluation of completeness, reproducibility, and the relation between the posted safety count and the study’s broader aims.

The study is listed as single center, which may also limit how readily its observations generalize to settings with different participants or clinical practices. These design and reporting limitations do not erase the observed events; they define the scope of conclusions that can be drawn from the registry summary.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Dose Tolerance, Pharmacokinetics, Pharmacodynamics of CPX-POM in Patients With Newly Diagnosed or Recurrent Bladder Tumors — NCT04525131.
• Registry record last updated 2024-06-18; status last verified 2024-05.
• Results first posted 2024-06-18.
• 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

NCT04525131 is a completed phase II, single-center, open-label, single-group study sponsored by CicloMed LLC. It enrolled 12 patients with newly diagnosed or recurrent bladder tumors and evaluated CPX-POM, administered intravenously over 20 minutes once per day. The study began on 2020-11-25 and reached primary completion on 2022-12-30.

The primary outcome was the number of participants with any serious adverse event in the safety population during 35 days, assessed using CTCAE version 5.0. The registry reports 1 participant with a serious adverse event among 12 at risk, 9 participants with other adverse events among 12 at risk, and 0 deaths. Hypoxia is listed as the top serious-event term at 8.3%.

The record contains no comparator group and lists no analyses. Results for treatment-related adverse events and the stated pharmacokinetic and pharmacodynamic aims are not reported in the registry record. The primary result is descriptive and does not provide a controlled treatment comparison.