Safety, Tolerability, and Pharmacokinetics of Iloperidone Depot in Schizophrenic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Pharmacokinetics of Iloperidone Depot in Schizophrenic Patients (NCT01348100), a randomized phase 1, phase 2 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B.

2. Clinical Question

3. Trial Design

The registry describes a randomized, open-label, parallel study with Phase 1 and Phase 2 components. It lists an enrollment of 81 and the condition as schizophrenia. The study is marked completed; the listed start is 2011-04 and primary completion is 2012-07. No masking was used.

The study had three parts. Phase A evaluated the safety of crystalline iloperidone depot at 50 mg and 125 mg, with each arm described as receiving one intramuscular injection after oral titration. Phase B compared the pharmacokinetic and safety profiles of crystalline and microparticle depot formulations at 250 mg. Each Phase B arm is described as receiving one injection after oral titration. Phase C evaluated three doses of a selected microparticle formulation: 250 mg, 500 mg, and 625 mg. The descriptions specify two depot injections 28 days apart for these Phase C arms, following oral titration.

The primary endpoint and the posted Phase B comparative results concern the 250 mg crystalline and 250 mg microparticle formulations. The stated primary pharmacokinetic population includes participants with evaluable pharmacokinetic data, and the two arm summaries give the analyzed numbers for this endpoint. The registry’s broad study enrollment should not be read as the analyzed number for this particular comparison. The record does not report a detailed account of how participants were assigned to phases or arms, nor does it report the original statistical design assumptions.

The study’s stated purpose was to evaluate safety, compare two depot dosage forms, and assess dose-ranging for one selected form in support of a monthly depot dosing regimen. Its design therefore includes formulation and dose exploration, rather than a comparison against a placebo or a non-iloperidone control.

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.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.

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: All participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B, measured over Pre-dose to 26 days post-dose.

The primary endpoint is the maximum observed plasma concentration of iloperidone divided by its average plasma concentration, abbreviated Cmax/Cav. It is a pharmacokinetic ratio: it relates the highest observed concentration to the average concentration over the measured dosing period. The registry reports the endpoint as a mean with standard deviation, with the ratio assessed from pre-dose to 26 days post-dose.

Concentration measurements were scheduled before dosing and at listed times after the injection. The registry says pharmacokinetic parameters were calculated from plasma concentration-time data using non-compartmental methods. This type of summary helps describe the shape and scale of drug exposure over time. A ratio such as Cmax/Cav can characterize how the observed maximum compares with the average, rather than describing either concentration alone.

For Phase B, the comparison is between the 250 mg crystalline and microparticle depot formulations. The reported means are 1.91 and 1.87, respectively. The reported mean difference for the microparticle formulation relative to the crystalline formulation is -0.04, with a confidence interval from -0.443 to 0.362. These summaries describe the posted pharmacokinetic results; they do not by themselves establish a clinical benefit or harm. The endpoint is a measure of plasma exposure, not a direct measure of symptoms or overall clinical outcome.

7. Results Posted in the Registry

• Iloperidone 250 mg Microparticle Formulation - Phase B: mean 1.87 versus 1.91 on control; difference -0.04 (95% CI -0.44 to 0.36), standardized effect d = -0.07; z-test p = 0.846.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Iloperidone 250 mg Microparticle Formulation - Phase B: mean 8.40 versus 6.25 on control; difference 2.15 (95% CI -0.29 to 4.59), standardized effect d = 0.66; z-test p = 0.084.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Iloperidone 250 mg Microparticle Formulation - Phase B and the control. The interval gives the range of effects that remain compatible with the data.

Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Iloperidone 250 mg Microparticle Formulation - Phase B: mean 3,190 versus 2,310 on control; difference 880.00 (95% CI -201.55 to 1,962), standardized effect d = 0.61; z-test p = 0.111.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Iloperidone 250 mg Microparticle Formulation - Phase B and the control. The interval gives the range of effects that remain compatible with the data.

Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Iloperidone 250 mg Microparticle Formulation - Phase B: mean 3,730 versus 2,890 on control; difference 840.00 (95% CI -336.42 to 2,016), standardized effect d = 0.53; z-test p = 0.162.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Iloperidone 250 mg Microparticle Formulation - Phase B and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary pharmacokinetic outcomes cover several features of concentration and exposure, including Cmax, AUCtau, and AUClast in Phase B, alongside other listed outcomes. For the three Phase B summaries with comparative estimates, the observed means are higher in the microparticle arm than in the crystalline arm. Their unadjusted mean-difference intervals include zero. This overall pattern is not identical to the primary Cmax/Cav result, which has a small negative point estimate. The measures address different aspects of the concentration-time profile, so their directions need not match.

These secondary outcomes provide context for the primary result by describing maximum concentration and exposure over the dosing period or to the last measurable concentration. They do not independently settle the primary formulation comparison. The registry lists 10 secondary outcomes as posted, while the record does not report sponsor analyses for the listed endpoint comparisons. The reported secondary summaries should therefore be understood as descriptive and exploratory evidence rather than a set of confirmatory conclusions.

Unadjusted secondary results carry less weight because multiple outcomes are examined without a reported multiplicity adjustment. In general, the more comparisons considered, the greater the opportunity for chance variation to produce an apparently striking result somewhere among them. Adjustment procedures or a prespecified hierarchy can address this issue, but neither is reported in the registry record. This does not make the measurements useless: they can describe pharmacokinetic profiles and help identify questions for later evaluation. It does mean that individual secondary p-values should not be treated as standalone confirmation.

The endpoints also come from a multi-part study that includes different phases and doses. An outcome from one phase may not directly answer the same question as an outcome from another. Interpretation should retain the phase, formulation, dose, and measurement definition attached to each result, rather than combining unlike measures into a single conclusion about the formulations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B
• Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B
• Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B
• Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B
• The Average Plasma Concentration (Cav) of Iloperidone - Phase B
• Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B
• Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C
• Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant contributes a pharmacokinetic ratio, and the arm summaries report a mean and standard deviation. A mean describes the central value of those observations. A standard deviation describes how spread out the participant-level values are around the mean. These are different quantities: the standard deviation is not a confidence interval and does not directly describe the precision of the comparison.

What does the mean difference represent?

The reported mean difference compares the microparticle arm with the crystalline arm by subtracting the crystalline mean from the microparticle mean. For the primary endpoint, the estimate is -0.04. A negative value means the observed mean was lower in the microparticle arm; it does not by itself establish that the formulations differ beyond sampling uncertainty. The confidence interval gives a range of values compatible with the observed data under the calculation’s assumptions. Because this interval extends from -0.443 to 0.362, it includes zero as well as values in either direction.

What does the p-value tell the reader?

The unadjusted p-value for this comparison is 0.846. In general, a p-value describes how unusual data at least as inconsistent with a specified no-difference model would be if that model and the analysis assumptions held. It is not the probability that the no-difference model is true, and it does not measure the probability that the observed difference arose by chance. It also does not indicate whether a difference is clinically important. The registry record does not report an adjusted p-value or a sponsor-reported analysis for this comparison.

Why do the confidence interval and p-value matter together?

The estimate gives a single summary of the observed contrast, while the interval communicates its uncertainty. The p-value gives a related test-based summary under a particular null model. For interpretation, the interval is especially useful because it displays the direction and range of plausible differences on the endpoint scale. Here, the interval includes zero and allows for values below and above zero. The data therefore do not tightly locate the comparative mean ratio.

What is the role of pharmacokinetic sampling?

The registry describes blood sampling before dosing and at scheduled times after injection, including measurements through Day 26. Non-compartmental methods were used to calculate pharmacokinetic parameters from the concentration-time data. In general, pharmacokinetic summaries depend on the timing and completeness of sampling, because measured concentrations provide the basis for estimating maxima, averages, and exposure over time. The registry record does not report further details on missing concentration measurements, imputation, or sensitivity analyses.

How should the secondary summaries be read?

The secondary outcomes include measures of maximum concentration, area under the concentration-time curve, average concentration, duration above a specified concentration, and timing of the maximum. These represent related but distinct features of drug exposure. A pattern across related pharmacokinetic outcomes can help describe the profiles, but it is not equivalent to a single prespecified primary test. The record lists multiple secondary outcomes and does not report multiplicity control. In general, when several outcomes are examined, unadjusted p-values do not account for the increased chance of apparently noteworthy findings across the set.

What are the limits of the recalculated comparisons?

The comparative mean differences, confidence intervals, and p-values are simple unadjusted recalculations from the posted group summary statistics. They should be distinguished from a sponsor’s own inferential analysis, which takes precedence when a discrepancy is recorded. No discrepancy is recorded for this trial. Still, these calculations do not supply information absent from the registry, such as covariate adjustment, analysis diagnostics, or a detailed prespecified statistical plan. The registry record reports no analyses in its analysis listing, so the available unadjusted comparisons should not be mistaken for a complete analysis report.

The planning illustrations are also separate from the observed comparison. They use the observed effect as a basis for illustrating participant requirements under stated assumptions. They are not a reconstruction of the trial’s original design, and they do not establish the power of the completed study. General power calculations depend on assumed effect size, variability, allocation, significance level, and the intended analysis; the original design assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

The primary comparison has a mean difference of -0.04, with a confidence interval from -0.443 to 0.362. This interval is wide relative to the point estimate and spans zero. It therefore indicates that the observed data do not pin down the direction of the underlying difference. Values in the interval are compatible with the recalculated comparison under its assumptions; the interval is not a guarantee that the true difference lies within it.

A confidence interval communicates precision as well as direction. A narrower interval would locate the estimated difference more tightly, while a wider interval leaves more uncertainty about its size. The primary interval allows for a negative difference and a positive difference, so the observed point estimate should not be over-read as evidence of a reliably lower ratio in the microparticle arm. Nor does inclusion of zero establish equivalence: an equivalence conclusion would require an appropriate margin and analysis, neither of which is reported in the registry record.

The group means are based on 13 participants for the crystalline formulation and 14 for the microparticle formulation. The standard deviations, 0.513 and 0.554, describe observed within-arm spread. In general, limited group sizes and participant-to-participant variability can make comparative estimates imprecise. The registry does not report a planned precision target or an original sample-size justification, so it is not possible to judge the result against a prespecified precision goal.

The confidence interval and unadjusted p-value are derived from recalculation of the posted summary statistics, rather than a reported sponsor analysis. They provide a transparent summary of uncertainty in this comparison, but they do not account for unreported analysis choices or any multiplicity strategy. The registry record reports no multiplicity adjustment. Precision should therefore be considered for this endpoint in context, rather than treated as a definitive statement about all pharmacokinetic outcomes or clinical effects.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations express the number of participants per arm for the two-arm continuous-outcome comparisons. They are not totals across arms and are not total event counts. For the primary endpoint, the illustration based on 100% of the observed effect gives 2,806 participants per arm for 80% power and 3,756 participants per arm for 90% power. For 75% of the observed effect, the corresponding figures are 4,987 and 6,677 participants per arm. For 50% of the observed effect, they are 11,221 and 15,022 participants per arm.

The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect that is the stated fraction of the observed effect. In plain terms, the 80% power column illustrates a design with an 80% chance of detecting the assumed effect under the calculation’s assumptions if that effect exists. The 90% power column uses a higher target chance of detection. These are planning illustrations, not observed power.

Smaller assumed effects require more participants to detect under the same general assumptions. That is why the illustrations increase as the target effect becomes a smaller fraction of the observed effect. The observed effect comes from a small Phase B comparison and is uncertain, so these figures should not be read as a reliable prescription for a future study. The original trial’s sample-size rationale and design assumptions are not reported in the registry record. The planning values are not evidence about the trial’s actual design or its ability to detect the observed result.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.040; pooled standard deviation σ = 0.535.
2. n = 2 × (1.96 + 0.842)² × 0.535² / -0.040² = 2,805.2, rounded up to 2,806 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.0399999999999998                      # observed difference in means
sigma <- 0.534712483489959                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1348100)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,806 (80% power), 3,756 (90% power)
 75% of observed effect: n per arm = 4,987 (80% power), 6,677 (90% power)
 50% of observed effect: n per arm = 11,221 (80% power), 15,022 (90% power)
power.t.test: 2806.1 
Simulated power at n = 2,806 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record describes a study with several aims and multiple phases: safety evaluation, comparison of two depot dosage forms, and dose-ranging of a selected form. It lists a primary Phase B pharmacokinetic endpoint and numerous secondary pharmacokinetic outcomes. The record does not report a statistical plan specifying how those outcomes were prioritized beyond the primary endpoint, nor does it report an adjustment for multiplicity. The posted comparative p-values are unadjusted recalculations from group summaries.

Multiplicity matters because testing several outcomes can increase the chance of at least one apparently noteworthy result arising from random variation. In general, an analysis plan may control this through adjustment or a prespecified testing sequence. Without such information, secondary p-values should be treated cautiously and viewed with their estimates and confidence intervals, rather than as independent confirmations. The registry record does not report whether interim analyses were planned or conducted.

The primary pharmacokinetic population is defined as participants with evaluable pharmacokinetic data. The registry reports 13 and 14 participants in the two primary endpoint arms, but does not provide a detailed account of exclusions, missing samples, or how missing data were handled. It does not report imputation methods or sensitivity analyses for missing pharmacokinetic observations. Those omissions limit assessment of whether the analyzed participants represent all participants assigned to the respective arms.

The registry also reports no analyses in its analysis listing and does not give a detailed inferential analysis plan. Thus, the posted summary statistics allow unadjusted comparisons, but do not establish which covariates, if any, were considered, how assumptions were checked, or whether alternative analyses were performed. The registry record does not report the original sample-size justification. These gaps should be kept distinct from what is observed: the reported means and variability remain useful descriptive information, but they do not provide a full account of the sponsor’s analytic decisions or missing-data processes.

15. 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: psychotic disorder (14.3%), extrapyramidal disorder (7.1%), social stay hospitalisation (7.1%), hospitalisation (7.1%).

The registry reports serious adverse event figures separately for the listed oral and depot exposure groups across Phases A, B, and C. For example, the Phase B depot groups list 2 serious events as affected in the crystalline group and 1 in the microparticle group, among 14 participants at risk in each listed group. These are group-specific registry entries; they should not be combined across exposure groups or interpreted as counts of unique participants across the whole study.

For other adverse events, the Phase B depot groups list 4 affected in the crystalline group and 8 in the microparticle group, each among 14 at risk. The corresponding Phase B oral groups list 9 and 10 affected, each among 15 at risk. The registry lists serious-event terms including psychotic disorder at 14.3%, and extrapyramidal disorder, social stay hospitalisation, and hospitalisation each at 7.1%. These term percentages are reported as recorded and should not be added together.

The deaths field is not populated for the listed groups, so deaths are not reported in the registry record. These safety counts are descriptive and span different phases and exposure periods. They do not by themselves establish comparative safety, particularly because the record does not provide a controlled statistical safety analysis for these figures.

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

The primary result describes a pharmacokinetic comparison between two 250 mg depot formulations in Phase B. The reported mean Cmax/Cav values are 1.91 for the crystalline formulation and 1.87 for the microparticle formulation. The recalculated mean difference is -0.04, with a confidence interval from -0.443 to 0.362 and an unadjusted p-value of 0.846. This is a comparison of a plasma concentration ratio, not a direct measure of symptoms, functioning, or overall clinical outcome.

The result does not establish that the formulations are equivalent. The confidence interval includes zero but also allows differences in either direction, and the registry record does not report an equivalence margin or an equivalence analysis. At the same time, the result does not establish a meaningful difference between the formulations. The estimate is uncertain, and the study’s small Phase B endpoint groups limit how precisely the comparison can be characterized.

The secondary pharmacokinetic measures describe additional properties of exposure, and the safety entries describe adverse events in groups across the study’s phases. Those results add descriptive context, but they do not change the definition of the primary endpoint or transform it into a clinical outcome. Nor do the safety counts alone demonstrate that a particular formulation is safer or less safe.

The study’s stated purpose included safety assessment, formulation comparison, and dose-ranging in support of a monthly depot regimen. The posted Phase B primary result addresses only one part of that broader purpose. It should not be generalized to all doses, all phases, or outcomes that were not measured or reported. The registry record does not report the original statistical design assumptions, a detailed analysis plan, a multiplicity strategy, or methods for handling missing pharmacokinetic data. These limitations leave important questions about design and inference unanswered.

In general, a pharmacokinetic study can characterize drug exposure and help inform later research. Its findings do not by themselves establish clinical effectiveness. The posted result is best read as an uncertain estimate of the difference in a specific exposure ratio between the two Phase B formulations, with the broader safety and dose-ranging information interpreted separately and cautiously.

17. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint matters. The primary outcome is not simply a drug concentration: it is the ratio of the maximum observed concentration to the average concentration. That distinction affects what the comparison means. The endpoint characterizes a feature of the concentration-time profile, while other secondary outcomes describe maximum concentration, area under the curve, or timing of the maximum.

It also illustrates the value of reporting both an estimate and its uncertainty. The mean difference of -0.04 is easy to quote, but the confidence interval from -0.443 to 0.362 shows that the estimate is not precise enough to settle the direction or magnitude of the comparison. A p-value alone would conceal that range. The group standard deviations and arm sizes add further context about variability and the amount of information supporting the estimate.

The multi-part design raises a broader interpretive issue. The study addresses two formulations and several dose levels in distinct phases, alongside safety and pharmacokinetic objectives. Those aims produce different kinds of evidence. A comparison at one dose and phase cannot automatically answer questions about other doses or a monthly regimen. Phase, formulation, dose, and endpoint definition all matter to the interpretation.

Finally, the record highlights the importance of a transparent statistical plan. It does not report the original sample-size justification, multiplicity strategy, detailed missing-data methods, or sponsor analyses for the posted endpoint comparisons. These gaps do not erase the descriptive results, but they constrain claims about confirmatory evidence. The planning illustrations show how assumptions about effect size and power can affect participant requirements, while remaining separate from the completed trial’s observed results.

18. 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 primary comparison is based on 13 participants in the crystalline arm and 14 in the microparticle arm, and the interval for the mean difference is broad enough to include values in both directions. The estimates should therefore be interpreted as imprecise. The registry’s overall enrollment is 81, but that figure is not the analyzed sample for this Phase B endpoint.

The registry record describes a randomized, open-label, parallel study, but does not report detailed allocation procedures or concealment. No masking was used. It also does not report the original sample-size rationale, so the relationship between the trial’s planned size and its intended precision or power cannot be assessed.

Pharmacokinetic outcomes depend on concentration measurements collected at scheduled times. The registry describes the sampling schedule and non-compartmental calculation methods, but does not report how missing or unevaluable samples were handled, whether all planned samples were obtained, or whether sensitivity analyses were conducted. The primary population is defined by evaluable pharmacokinetic data, which makes those details relevant to assessing the analysis.

The record lists multiple secondary outcomes and does not report multiplicity adjustment or a prespecified secondary testing strategy. The posted unadjusted comparisons are recalculations from summary statistics, not a full sponsor analysis. In addition, the trial’s multi-phase structure and different doses limit simple generalization from the Phase B 250 mg comparison to the Phase A or Phase C arms. The registry does not report clinical outcome comparisons that would establish the implications of the pharmacokinetic findings for symptoms or functioning.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Pharmacokinetics of Iloperidone Depot in Schizophrenic Patients — NCT01348100.
• Registry record last updated 2014-01-22; status last verified 2013-12.
• Results first posted 2013-10-08.
• 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.

22. Record Summary

NCT01348100 is a completed randomized, open-label, parallel Phase 1 and Phase 2 study in participants with schizophrenia. The registry lists enrollment of 81, a start of 2011-04, and primary completion in 2012-07. The study had three parts: Phase A safety assessment of crystalline depot formulations, Phase B comparison of crystalline and microparticle formulations, and Phase C dose-ranging of a selected microparticle formulation.

The primary posted comparison is the Phase B Cmax/Cav ratio for 250 mg formulations. The means were 1.91 for crystalline and 1.87 for microparticle; the unadjusted mean difference was -0.04, with a confidence interval from -0.443 to 0.362 and p = 0.846. The result is uncertain and does not establish equivalence or a clinically meaningful difference.

The registry also reports secondary pharmacokinetic summaries and adverse-event figures across phases. It does not report a detailed statistical plan, multiplicity strategy, original sample-size justification, or missing-data methods for the pharmacokinetic analysis.