One-Year Trial of Oral Ziprasidone in Bipolar Patients With Metabolic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for One-Year Trial of Oral Ziprasidone in Bipolar Patients With Metabolic Syndrome (NCT01113541), a non-randomized phase 3 study. The primary outcome is Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation.

2. Clinical Question

The study explored the distribution of metabolic-syndrome risk factors in a group of bipolar patients who had relevant metabolic concerns while taking their current antipsychotic medication. The primary outcome focuses on whether the number of risk factors decreased, rather than on a comparison between treatments.

The registry lists risk factors involving waist circumference, triglycerides, HDL cholesterol, fasting glucose, and systolic or diastolic blood pressure. Its responder definition is a reduction of at least one risk factor at the endpoint compared with baseline. That makes the primary question a within-participant change question, but the record does not supply the observed percentage or other endpoint results.

Because there was no control group and no random allocation, the study cannot make a randomized comparison between ziprasidone and another treatment. The question is descriptive: what happened among participants assessed after switching to oral ziprasidone? The registry record does not report the primary endpoint result, so the size or direction of any observed change cannot be described.

3. Trial Design

This was a Phase III, open-label, non-randomized, non-comparative, single-group trial of oral ziprasidone in patients with bipolar disorder. The registry lists enrollment of 13. The study status is terminated. Its listed start was 2010-07 and its primary completion was 2011-02; the reason for termination is not reported in the registry record.

Participants switched to oral ziprasidone, with no control arm described. Open-label means that treatment masking was absent, as the registry also records masking as none. A single-group design can describe outcomes observed over time in participants receiving the intervention, but it does not provide a concurrent group for separating changes associated with treatment from changes due to other influences. General: random allocation and masking are design tools that can reduce particular forms of bias in a comparison; neither creates a comparator where none exists.

The primary endpoint was the percentage of participants who achieved a reduction from baseline of at least one metabolic-syndrome risk factor at Week 52 or premature discontinuation. The endpoint’s stated population was per protocol: participants in the intent-to-treat population who remained in the study for at least 28 weeks. The registry explains that the N at an observation represents participants with analyzable data at that observation. It does not report the analyzable count for the primary endpoint.

The record lists 30 outcome measures and several secondary outcomes, including mean change in the number of risk factors, metabolic-syndrome prevalence, and individual risk-factor measures. It lists zero analyses. The statistical analysis plan, any interim analyses, and the reason for selecting the per-protocol population are not reported in the registry record.

The tables and plots should be read as displays of the posted results, not as evidence of a controlled treatment effect. The primary endpoint result itself is not reported in the registry record. Any interpretation must therefore distinguish the endpoint that was specified from results that are actually available.

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: Twenty-seven participants were screened for the study and 13 participants were assigned to study drug and treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol population: all subjects in the intent-to-treat population who remained in the study for at least 28 weeks. N = number of participants with analyzable data at observation.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved a Reduction From Baseline of at Least 1 Risk Factor for Metabolic Syndrome (MS) at Week 52 or Premature Discontinuation, measured over Week 52 or Early Termination.

The primary endpoint is the percentage of participants who had at least one fewer metabolic-syndrome risk factor at Week 52 or early termination than at baseline. A participant counted as a responder if the number of risk factors at the endpoint was lower than at baseline by at least one. The registry identifies risk factors involving waist circumference, triglycerides, HDL cholesterol, fasting glucose, and blood pressure.

This endpoint reduces several measurements to a responder classification: whether the participant met the stated reduction criterion or did not. Such a summary can be useful when the question concerns improvement across a set of clinically relevant risk markers, rather than a change in only one measurement. General: a composite or count-based endpoint can summarize several dimensions, but it may conceal which component changed and whether different participants changed in different ways. The listed secondary outcomes address several of those component-level questions.

The timepoint is Week 52 or premature discontinuation, and the primary endpoint population is per protocol. The record says that participants had to remain in the study for at least 28 weeks to be included in that population. It does not report the primary endpoint percentage, its numerator or denominator, an uncertainty interval, or a test result. The endpoint definition is therefore available, but the posted information does not establish how many participants met it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: statistical methods translate an outcome definition into a summary and, when appropriate, an estimate of uncertainty. For this trial, the endpoint definition is available, but the registry record does not report the primary estimate or an analysis method for it. The method discussion below distinguishes what the endpoint means from what cannot be learned from the posted record.

What does the responder endpoint summarize?

The endpoint classifies participants according to whether they had at least one fewer metabolic-syndrome risk factor at the endpoint than at baseline. It then expresses the outcome as a percentage of participants. This is a binary classification at the participant level: meeting the responder definition or not meeting it. It is not the same as reporting the mean change in each laboratory or clinical measurement. The registry lists those individual risk-factor changes among secondary outcomes.

General: a percentage is most informative when its denominator is clear. Here the endpoint’s population is described as per protocol, and the registry says that N at an observation means participants with analyzable data at that observation. But the actual endpoint denominator and responder count are not reported in the registry record. Without them, the percentage cannot be checked or interpreted for precision.

What does uncertainty mean?

General: an uncertainty interval describes a range of values compatible with the observed data under a specified statistical method and its assumptions. It helps readers judge how precise an estimate is; an estimate alone does not show its uncertainty. The registry record does not report a confidence interval for the primary endpoint, nor does it report a primary endpoint test or p-value. No inference about precision or statistical significance can be drawn from the endpoint definition alone.

General: for a percentage based on a small group, each participant’s classification can have a noticeable influence on the overall estimate. This is a reason to read the numerator, denominator, and uncertainty interval together when they are available. The registry lists enrollment of 13, but enrollment is not necessarily the denominator for the per-protocol endpoint. The endpoint denominator is not reported in the registry record.

How should the design shape the analysis?

This is a single-group study with no randomized comparator. A within-participant comparison of endpoint with baseline can describe observed change, but it does not estimate a contrast against a concurrent control group. General: randomization is commonly used to make treatment groups comparable in expectation, while a concurrent comparator helps account for changes that may occur over time independently of the intervention. Neither feature is present. The record does not report an adjusted analysis or a model for the primary endpoint.

The endpoint uses a count of risk factors to decide whether a participant responded. General: reducing a collection of component measures to one summary may aid communication, but it can hide different patterns among the components. For example, the same responder classification could arise from changes in different risk factors. The registry lists secondary outcomes that include both an overall risk-factor count and individual risk-factor measures, but their results are not reported.

What can be inferred from the sample-size illustration?

The sample-size section is described as a planning illustration computed from the observed effect, not as the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record says that non-time-to-event illustrations give participants per arm. Those assumptions describe the illustration, not this trial: the trial was a single-group, non-comparative study. The illustration is not observed power, and it does not explain why enrollment was 13. A sample-size justification is not reported in the registry record.

General: power is a design concept about the chance of detecting a specified effect under assumed conditions. It is not a measure of whether a study result is true, and calculations based on an observed effect do not substitute for a prespecified design justification. The illustration should therefore be read as a hypothetical planning aid, not as evidence about the trial’s ability to establish an effect.

What is not specified?

The registry record does not report the primary analysis method, a missing-data method, covariate adjustment, handling of multiple comparisons, or interim analyses. It lists zero analyses. General: these choices can affect how an estimate is produced and how uncertainty is assessed, so they matter when interpreting a clinical trial. They cannot be reconstructed from the endpoint definition or from the study title.

For any displayed results, readers should keep the endpoint population, available denominator, and design in view. Here, the posted record defines the endpoint and population but does not provide the primary estimate or its uncertainty. The most defensible statistical reading is therefore descriptive and limited to the information explicitly 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("Ziprasidone")
n      <- c(10)
events <- c(5)
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  Ziprasidone  10  5  50.0  18.7  81.3  23.7  76.3  23.4  76.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures, including a primary endpoint and multiple secondary outcomes covering risk-factor counts, prevalence, and individual components. It lists zero analyses. A statistical plan describing how the outcomes were prioritized or how multiple testing was handled is not reported in the registry record.

General: when a study assesses many outcomes, the chance of finding an apparently notable result among them can depend on how many comparisons are made and how they are interpreted. Methods for controlling or otherwise addressing multiplicity should be specified in the analysis plan. Because such a plan is not reported, the record does not establish whether any adjustment or hierarchy was used. The outcome list alone does not show that every listed measure was tested or how results should be prioritized.

The record defines the primary analysis population as participants in the intent-to-treat population who remained in the study for at least 28 weeks. It also defines N at an observation as the number of participants with analyzable data. The number with analyzable primary endpoint data, the number excluded from the per-protocol population, and the reasons for missing data are not reported in the registry record. A missing-data method is not reported either.

General: missing observations can affect both the denominator and the interpretation of an estimate, particularly if participants with missing outcomes differ from those with observed outcomes. The record does not provide enough information to assess whether missingness could have influenced the endpoint result. The absence of a reported result also prevents comparison of analyses based on different populations or assumptions.

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: akathisia (7.7%).

The registry’s safety summary lists 13 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 13 participants at risk and 13 affected. These are counts of participants in the safety summary; they should not be read as counts of all event episodes, since a participant may experience more than one event. The record lists akathisia at 7.7% among the top serious adverse-event terms.

The deaths entry is not reported in the registry record. The summary does not establish whether each event was caused by ziprasidone. General: adverse-event summaries describe events recorded during a study; attribution and causality require separate assessment and cannot be inferred solely from the number of participants affected.

The safety figures come from a single-group study with enrollment of 13. There is no control group against which to compare event frequencies. These figures therefore describe the posted safety summary for this study and should not be interpreted as comparative rates. The registry record does not provide further detail about event timing, duration, severity beyond the serious-event classification, or individual participant circumstances.

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

The result available from the registry is primarily a definition of the question the investigators intended to assess: whether participants had at least one fewer metabolic-syndrome risk factor at Week 52 or early termination than at baseline. The registry record does not report the observed percentage meeting that definition. It also does not report the endpoint denominator, confidence interval, or test result. Accordingly, the posted record does not show how often the endpoint was achieved or how precisely it was estimated.

Even if the endpoint result were available, the design would remain important. This was a non-randomized, open-label, single-group trial with no comparator. A change from baseline could describe what was observed among participants, but it could not by itself show that the change was caused by the intervention or how it compares with another treatment. General: a control group and random allocation help address alternative explanations and differences between groups; they are absent from this design.

The endpoint’s responder definition does not indicate which risk factor changed, the size of change in any individual measurement, or whether all participants had similar patterns. The registry lists secondary outcomes that could provide more detail, but their results are not reported in the registry record. The composite definition is therefore not a substitute for component-level results.

The trial’s enrollment was 13, and its status is terminated. Those details describe the study, but the reason for termination is not reported in the registry record. They do not justify an assumption about the results or about why the study ended. The planning illustration on the page is not observed power and is not the trial’s sample-size justification.

The appropriate conclusion is limited: the record specifies a clinical question and endpoint, and describes the single-group design and safety counts. It does not provide the primary outcome result needed to estimate the observed endpoint or its precision. No treatment recommendation or comparative treatment conclusion follows from these data.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its stated endpoint can sound comparative or definitive while its design is explicitly non-comparative. The primary question concerns change from baseline in participants who switched to oral ziprasidone. With one group and no random allocation, the design can describe observations over time but cannot provide a randomized comparison with another treatment or a control condition.

The endpoint also illustrates the difference between a responder summary and the underlying measurements. Its definition combines several metabolic-syndrome risk factors into a criterion based on having at least one fewer risk factor. That approach provides a clear classification, while potentially concealing which component changed. The registry’s listed secondary outcomes show why examining both an overall summary and individual components can matter; their results are not reported.

The record also distinguishes enrollment from the analysis population. It lists enrollment of 13, but defines the primary population as per protocol and requires participants to remain in the study for at least 28 weeks. It further defines N at an observation as the number with analyzable data. These details make the endpoint denominator essential for interpretation, yet that denominator is not reported in the registry record.

Finally, the posted sample-size illustration is based on a two-arm planning setup, while this trial is a single-group study. Treating a planning illustration as the trial’s design or as observed power would confuse distinct statistical ideas. The record does not report the trial’s sample-size justification or primary analysis plan. The case therefore highlights the need to read endpoint definitions, analysis populations, missingness, and design together rather than relying on a study title or a single summary measure.

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.

Several limitations follow directly from the registry record. The study was open-label, non-randomized, single-group, and non-comparative. No control arm is described, so there is no like-for-like basis for comparing outcomes with another treatment. Any observed within-group change would not, by itself, separate the intervention from other influences over time.

The record lists enrollment of 13, but the primary endpoint uses a per-protocol population of participants who remained in the study for at least 28 weeks. The number meeting that definition and the number with analyzable data at the primary endpoint are not reported in the registry record. The reasons for any missing observations or exclusions are also not reported, making the consequences of attrition difficult to assess.

The study status is terminated, but the reason for termination is not reported in the registry record. The primary endpoint result, its uncertainty, and the primary analysis method are not reported. Although the record lists 30 outcome measures, it does not report a multiplicity strategy or an analysis hierarchy. Interim analyses, a missing-data method, and a sample-size justification are not reported in the registry record.

The endpoint itself summarizes several risk factors using a responder threshold. Without the primary result and the secondary outcome results, readers cannot assess the frequency of response, its precision, or which individual risk factors contributed to any change. The safety summary provides participant counts and a serious adverse-event term, but no comparison group is available to contextualize those counts. These limitations restrict interpretation to the design and information explicitly documented.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: One-Year Trial of Oral Ziprasidone in Bipolar Patients With Metabolic Syndrome — NCT01113541.
• Registry record last updated 2021-03-03; status last verified 2021-03.
• Results first posted 2012-07-09.
• 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 describes a Phase III, open-label, non-randomized, non-comparative, single-group trial of oral ziprasidone in patients with bipolar disorder and metabolic-syndrome risk factors associated with their current antipsychotic medication. Enrollment was 13. The record lists the study as terminated, with start in 2010-07 and primary completion in 2011-02.

The primary endpoint was the percentage of participants with at least one fewer risk factor at Week 52 or early termination than at baseline. Its population was per protocol, defined as participants in the intent-to-treat population who remained in the study for at least 28 weeks. The registry does not report the primary endpoint result, analyzable denominator, or uncertainty interval.

The record lists 30 outcome measures and zero analyses. It reports safety counts, including 1 participant affected by a serious adverse event among 13 at risk, and lists akathisia at 7.7% among top serious terms. The reason for termination and the analysis plan are not reported in the registry record.