Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone (NCT03978832), a na phase 4 study. The primary outcome is Steady-state Average Plasma Concentration (Cavg,ss) of Risperidone and Total Active Moiety.

2. Clinical Question

The study concerned a higher PERSERIS dose than the brief summary says had been used in previous clinical trials. That summary describes switching participants stable on 5-6 mg oral risperidone to the higher dose, which it says was believed to be similar to the oral dose. This is the rationale as worded in the registry record, not a reported finding that the treatments produce equivalent exposure or outcomes.

The clinical question therefore has a descriptive, within-participant pharmacokinetic focus rather than a randomized treatment-effect comparison. Secondary outcomes listed in the record include injection-site tolerability, treatment-emergent adverse events assessed in several ways, extrapyramidal symptoms, and the Positive and Negative Syndrome Scale (PANSS). The registry record does not report numerical results for those outcomes.

3. Trial Design

This was a phase 4, open-label, single-group study with no randomized allocation. The registry lists schizophrenia as the condition and describes participants as clinically stable on oral risperidone before switching to PERSERIS. Enrollment was 69. The study status is completed; the recorded start date is 2019-06-28 and the primary completion date is 2020-05-12.

The arm was described as oral risperidone followed by PERSERIS. Participants received subcutaneous injections according to a repeated-visit schedule: 2 injections at each visit every 28 days for a total of 4 visits. The first 3 visits used abdominal injection sites, while injections at the final visit were administered in the back of the upper arm. The study title identifies the switch as from 6 mg oral risperidone to 180 mg subcutaneous risperidone.

The primary endpoint was pharmacokinetic. It concerned steady-state average plasma concentration, abbreviated Cavg,ss, for risperidone and total active moiety. The registry describes assessment during 0-12 hours post-dose on Day -1 for oral administration and 0-672 hours after Dose 3 for subcutaneous administration. The primary pharmacokinetic analysis population required receipt of at least 3 PERSERIS doses and adequate blood samples after the third dose.

Because the study was single-group and open-label, it did not include a concurrent randomized control group. The oral and subcutaneous periods can be understood as measurements around a treatment switch, but the registry record does not specify a randomized sequence or a controlled comparison. It also does not report a protocol-level statistical analysis plan, sample-size justification, or interim-analysis plan. The enrollment figure is a record of enrollment, not evidence by itself about the precision of the endpoint estimates.

The record lists 19 outcome measures and no analyses. It includes pharmacokinetic, safety, tolerability, and symptom measures, but the available record does not give numerical results for the primary pharmacokinetic endpoint or the listed secondary outcomes. Consequently, the design and planned assessments can be described, while estimates of treatment effects cannot be reconstructed from this 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.

Before assignment: After providing informed consent potential participants were screened, and after eligibility was confirmed, participants were stabilized on 6 mg daily of oral risperidone (3 mg administered twice a day \[BID\] approximately 12 hours apart) for 5 days. After completion of the stabilization period, participants were eligible to receive 180 mg PERSERIS (subcutaneous risperidone), administered as two 90 mg SC injections every 28 days.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary PK analysis was conducted in participants who received at least 3 doses of PERSERIS 180 mg and provided adequate blood samples for the determination of Cavg after the third dose (primary PK 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: The baseline number is the number of participants who received oral risperidone during the stabilization period and at least one PERSERIS injection. This equals the number of participants included in the safety and efficacy populations. There was one additional participant included in the PK population who had PK data from oral risperidone but did not receive PERSERIS and was not included in the safety population.

6. Primary Endpoint

The registry lists the primary outcome as Steady-state Average Plasma Concentration (Cavg,ss) of Risperidone and Total Active Moiety, measured over 0-12 hours post-dose on Day -1, and 0-672 hours after Dose 3.

The primary endpoint is steady-state average plasma concentration, Cavg,ss, for risperidone and total active moiety. It is reported in ng/mL, with the parameter specified as a geometric mean and dispersion specified as a geometric coefficient of variation. The registry describes measurements during 0-12 hours post-dose on Day -1 for oral risperidone and during 0-672 hours after Dose 3 of PERSERIS.

As a general pharmacokinetic concept, an average concentration over a defined interval describes drug exposure across that interval rather than at a single sampling moment. Steady-state measures are used to characterize exposure after repeated dosing has reached a stable pattern. The total active moiety combines the pharmacologically active risperidone-related material as defined for the endpoint; the record does not provide further details of its calculation.

Geometric means are commonly used for concentration measures when values are positive and their distribution is skewed. A geometric coefficient of variation describes relative dispersion on a multiplicative scale. These summaries can help characterize exposure and variability, but they do not alone establish equivalence, clinical benefit, or safety.

The registry record identifies the endpoint and the pharmacokinetic analysis population, but does not report the observed geometric means, dispersion values, confidence intervals, or a numerical comparison between the oral and subcutaneous periods. Thus, the endpoint’s intended measurement is clear, while the magnitude and precision of the observed concentrations are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an open-label, single-group study. In a randomized parallel-group trial, allocation creates groups that can be compared under a planned treatment contrast. Here, allocation is listed as not applicable and the model is single-group. The oral-to-subcutaneous sequence is therefore not a randomized comparison against a separate control group. General statistical interpretation should distinguish a description of measurements before and after a switch from a controlled estimate of what would have happened under an alternative treatment strategy.

The primary outcome is a concentration measure, Cavg,ss, for risperidone and total active moiety. As a general concept, pharmacokinetic concentration measurements characterize drug exposure in the body over time. An average over a specified interval represents exposure across that interval; it is different from a single concentration at one sampling time. The record gives the oral assessment interval as 0-12 hours post-dose on Day -1 and the subcutaneous assessment interval as 0-672 hours after Dose 3. Those intervals define what the endpoint is intended to summarize, but the record does not include the observed concentration summaries.

The specified summary is a geometric mean. In general, geometric summaries are useful for positive measurements whose variability is better understood in multiplicative rather than additive terms. The geometric mean is based on the logarithmic scale and then expressed on the original scale. This makes it a common summary for concentration data. The registry also names a geometric coefficient of variation as the dispersion measure. In general, this describes relative variability on a multiplicative scale; it is not the same as a standard deviation expressed in ng/mL.

These choices affect interpretation. A geometric mean describes a central exposure level, while a measure of dispersion describes how much observations vary around that level. Neither summary by itself indicates whether two periods are equivalent. A comparison would require an estimate of the contrast, an uncertainty measure, and an interpretation rule. A confidence interval, as a general statistical tool, conveys the range of values compatible with the data and model at its stated confidence level. The registry record does not report confidence intervals for this endpoint, so its precision cannot be assessed from the record.

The primary pharmacokinetic analysis population is defined by receipt of at least 3 doses of PERSERIS 180 mg and provision of adequate blood samples to determine Cavg after the third dose. This is an analysis-population criterion, not the enrollment count. In general, specifying a population clarifies which participants contribute to a particular endpoint. However, the registry does not state the number meeting this criterion, how adequacy of samples was determined, whether all qualifying participants contributed at every sampling time, or how incomplete profiles were handled.

Missing-data methods matter because concentration estimates may depend on the timing and completeness of blood samples. As a general point, excluding participants with incomplete sampling can change the composition of the analyzed group if missingness is related to participant characteristics or outcomes. Other approaches may make different assumptions about unavailable measurements. The registry record does not report an approach for missing data, so no particular method or assumption should be attributed to the study.

The record also gives a planning-illustration framework: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. They do not change the actual single-group design described in the registry. The registry does not report the trial’s own sample-size justification, and no numerical planning estimates are reported in the information available.

General power calculations estimate how often a specified analysis might detect a specified effect under stated assumptions. They depend on the effect size, variability, analysis method, significance level, and allocation. A planning illustration based on an observed effect uses an effect estimate from data and should not be read as a prospective design justification. Nor is it observed power: after data collection, the observed estimate and its uncertainty are more informative than a retrospective calculation of power. No power value or sample-size result is reported in the registry record.

Multiplicity is another general concern when a study includes multiple outcomes or tests. Testing many hypotheses can increase the chance of at least one false-positive result if all are interpreted without adjustment. Possible approaches include defining a primary testing hierarchy or adjusting inference across a family of outcomes. The registry lists 19 outcome measures but no analyses. It does not report which secondary outcomes were formally tested, what testing hierarchy was used, or whether any adjustment was applied. Therefore, the multiplicity strategy cannot be determined.

Over-dispersion is a general issue when count outcomes vary more than a simple statistical model expects. In that setting, standard errors from a model that assumes less variability may be too small, leading to intervals that are too narrow and tests that are too optimistic. This concept is not a reported finding about this study: the registry does not identify a count-model analysis or provide model diagnostics. It is relevant only as a general reminder that analysis methods should match the outcome distribution.

The safety counts have a different interpretation from the concentration endpoint. They report participants affected within the recorded safety group, not exposure summaries or treatment-effect estimates. An adverse-event count can describe what was recorded, but causal attribution and comparative risk assessment require additional design and analysis information. The registry record does not provide a separate randomized safety comparator, detailed person-time, or event-level timing and severity information. The counts should therefore be read descriptively and within the denominators stated, without extending them to a causal comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary pharmacokinetic endpoint and secondary measures related to injection-site tolerability, treatment-emergent adverse events, extrapyramidal symptoms, and PANSS. It reports no analyses. This means the record does not provide a statistical testing map showing which outcomes were analyzed, what comparisons were made, or how results were prioritized.

As a general statistical issue, evaluating many outcomes can create multiplicity: when several hypotheses are tested, the chance of at least one apparently significant finding can increase. Researchers may address this through prespecified testing sequences, adjustment procedures, or by treating some outcomes as exploratory. The registry record does not report whether any such approach was planned or used. No multiplicity adjustment should be inferred from the outcome list alone.

The primary pharmacokinetic population is defined as participants who received at least 3 PERSERIS doses and provided adequate samples for determining Cavg after the third dose. The number meeting this definition is not reported in the registry record. Nor does the record state the number contributing to each endpoint or explain how measurements that were missing, incomplete, or unusable were treated.

These omissions limit assessment of possible selection due to missing data and limit the ability to reproduce the analysis. As a general matter, complete-case analyses, imputation, and model-based methods rely on different assumptions; the method used can affect estimates and uncertainty. The registry record does not identify any of these methods for this study. It also does not report sensitivity analyses addressing missingness.

The record does not report an interim-analysis plan, a detailed statistical analysis plan, or a sample-size justification. Those details should be treated as unreported rather than assumed absent from the study’s broader documentation. The listed enrollment and completed status do not resolve these questions.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: increase in liver enzymes (4.3%).

The registry’s adverse-event group is titled “Oral Risperidone Followed by PERSERIS.” For serious adverse events, it lists 23 at risk and 1 affected. For other adverse events, it lists 23 at risk and 9 affected. It records 0 deaths. These are descriptive counts for the group and denominators stated; they are not a randomized comparison with another treatment group.

The record identifies “increase in liver enzymes” as a top serious adverse-event term at 4.3%. The percentage is reported as a term-level figure, but the registry information does not explain its denominator or provide further event-level detail. It should not be converted into an assumed participant count or interpreted as a rate over a specified follow-up period.

Counts of participants affected do not convey the full clinical context of events. The registry record does not report event timing, severity, duration, resolution, or a detailed assessment of causal relationship. It also does not give a comparison that could distinguish event frequency under this regimen from frequency under another regimen. The figures therefore describe recorded safety outcomes without establishing comparative risk or causation.

The serious-event and other-event denominators are both listed as 23, while enrollment is listed as 69. The record does not explain the difference, so it should not be assumed that the safety denominators represent all enrolled participants or that a particular reason accounts for the discrepancy.

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

The study addresses a focused pharmacokinetic question in clinically stable participants with schizophrenia who switched from oral risperidone to subcutaneous PERSERIS 180 mg. The record gives the endpoint definition, measurement windows, summary scale, and rule for the primary pharmacokinetic population. These details clarify what investigators intended to measure and who could contribute to that analysis.

However, the registry record does not report the numerical Cavg,ss results, their geometric coefficients of variation, confidence intervals, or a formal comparison between administration periods. It therefore does not show the observed size or precision of the pharmacokinetic measurements. The design description and endpoint definition cannot substitute for those estimates.

The design also does not establish a randomized treatment contrast. This was an open-label, single-group study, with oral risperidone followed by PERSERIS rather than a separate randomized control arm. Measurements from the two administration periods may be informative descriptively, but the record does not provide a controlled estimate that isolates the effect of treatment from other influences over time.

The listed secondary outcomes cover safety, tolerability, and symptoms, but their numerical results are not reported in the registry record. The adverse-event counts are descriptive and have no concurrent randomized comparator in this record. They should not be interpreted as proof that an outcome improved, worsened, or was unchanged. Likewise, the study’s completed status is administrative information, not an efficacy or safety result.

Accordingly, the strongest supported interpretation is about scope: the trial assessed pharmacokinetics following a switch and included a range of safety and symptom outcomes. The available record does not support conclusions about clinical benefit, equivalence of exposure, comparative safety, or the magnitude of any change. Those conclusions would require results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically useful to examine because it illustrates the difference between a clearly specified endpoint and a reported estimate. The registry defines a pharmacokinetic measure, its units, a geometric summary, a dispersion measure, measurement intervals, and an analysis-population rule. That information makes the intended question interpretable even though the numerical answer is not reported.

It also highlights how design determines the strength and type of inference. A single-group, open-label switch study can describe assessments made during oral and subcutaneous treatment periods. Without a randomized comparison group, it does not provide the same basis for causal comparison as a randomized controlled design. The distinction matters when a reader considers whether observed differences, if reported, could be attributed to the switch itself.

The study also makes analysis-population definitions important. Enrollment is not automatically the denominator for every endpoint. The primary pharmacokinetic population requires at least 3 doses and adequate blood samples after the third dose, while the safety group has its own stated denominators. Reporting how many participants contribute to each analysis and how incomplete observations are handled is important for understanding representativeness and precision.

Finally, the record lists a broad set of outcomes but no analyses. This underscores why outcome lists alone do not establish findings, and why multiplicity plans and numerical estimates matter when several endpoints are assessed. For biostatisticians and clinical researchers, the case separates design information, endpoint specification, analysis-population rules, and results—components that should not be treated as interchangeable.

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.

The most important limitation for interpreting results is that numerical results for the primary pharmacokinetic endpoint are not reported in the registry record. The record gives neither the geometric mean concentrations nor the geometric coefficients of variation, and it does not report a contrast or confidence interval. As a result, the magnitude and precision of the pharmacokinetic findings cannot be assessed.

The design is open-label and single-group, with no randomized comparison arm. The registry describes an oral-to-subcutaneous sequence, but does not report a controlled estimate separating the effect of the switch from other changes over time. A pre-switch measurement is not equivalent to a concurrent randomized control.

The primary analysis population requires at least 3 PERSERIS doses and adequate blood samples after Dose 3, but the number meeting that definition is not reported. The record does not explain how missing or unusable samples were handled, or provide endpoint-specific denominators. These omissions make it difficult to assess completeness and potential selection in the pharmacokinetic analysis.

The adverse-event denominators are 23 for serious events and 23 for other events, while enrollment is 69. The record does not explain the difference. It also does not provide detailed event timing, severity, duration, or causal assessments. Therefore, the safety counts cannot be expanded into a comprehensive comparative safety interpretation.

Although 19 outcome measures are listed, the record reports no analyses. Statistical methods, multiplicity handling, sample-size justification, and interim analyses are not reported in the registry record. The record’s status as completed and its enrollment figure do not fill those information gaps.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone — NCT03978832.
• Registry record last updated 2021-07-07; status last verified 2021-06.
• Results first posted 2021-07-07.
• 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

This completed phase 4 study, NCT03978832, was an open-label, single-group study of a switch from oral risperidone to PERSERIS 180 mg in participants with clinically stable schizophrenia. Enrollment was 69. The recorded study start date was 2019-06-28 and primary completion date was 2020-05-12.

The primary endpoint was steady-state average plasma concentration of risperidone and total active moiety, summarized by geometric mean with geometric coefficient of variation. The primary pharmacokinetic population required at least 3 PERSERIS doses and adequate blood samples after the third dose. Numerical primary endpoint results are not reported in the registry record.

The record lists 19 outcome measures and no analyses. It reports adverse-event counts of 1 affected among 23 at risk for serious events, 9 affected among 23 at risk for other events, and 0 deaths. A top serious-event term, “increase in liver enzymes,” is listed at 4.3%. The record does not provide a randomized comparator.