Safety and Efficacy of Cariprazine (RGH-188) in the Acute Exacerbation of Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Cariprazine (RGH-188) in the Acute Exacerbation of Schizophrenia (NCT00694707), a randomized phase 2 study. The primary outcome is Change From Baseline to Week 6 in the PANSS Total Score.

2. Clinical Question

The registry describes the study as an evaluation of the safety, efficacy, and tolerability of cariprazine relative to placebo in adults with acute exacerbation of schizophrenia. Its listed interventions and arm descriptions show that the study also included risperidone as an active comparator. The primary outcome was change from baseline to Week 6 in the PANSS total score; change in the CGI-S score over the same interval was listed as a secondary outcome.

The clinical question therefore concerns both the direction and size of symptom-score change, as well as how precisely any group differences were estimated. The registry record does not report the primary-outcome values needed to quantify such differences in a single comparison. The record also does not report the numerical secondary-outcome results. Consequently, the design and outcome definitions can be described, but the available information does not support a numerical account of comparative symptom change.

3. Trial Design

This was a phase 2, randomized, double-blind, parallel-group trial. The registry lists 732 participants enrolled and identifies schizophrenia as the condition studied. The study began on 2008-06-30, reached primary completion on 2009-08-31, and has a completed status in the registry record. Forest Laboratories is listed as the sponsor.

Participants were adults 18-60 years of age with an acute exacerbation of schizophrenia. The arm descriptions specify five regimens, each taken orally once a day for 6 weeks: placebo; cariprazine 1.5 mg, 3.0 mg, or 4.5 mg; and risperidone 4.0 mg. Random allocation means participants were assigned to treatment groups by a random process, while double masking means the record identifies the trial as masked for two parties. The identities of those parties and the practical masking procedures are not reported in the registry record. A parallel-group design assigns participants to a group whose treatment is followed during the study rather than describing a crossover between treatments.

The brief study description emphasizes cariprazine relative to placebo, while the listed arms also include risperidone. The record does not report the allocation ratio, the method used to generate or conceal the allocation sequence, or details of site organization. It also does not report a statistical analysis plan or a sample-size justification. The enrollment figure describes the trial record; it should not be mistaken for the number included in every outcome analysis. For the primary outcome, the registry defines a narrower analysis population based on treatment exposure and availability of a post-baseline PANSS assessment.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: All participants who took at least 1 dose of double-blind investigational product and who had at least 1 post-baseline assessment of the primary efficacy parameter, the PANSS total score.

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 randomized participants who took at least 1 dose of double-blind investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 6 in the PANSS Total Score, measured over Baseline to Week 6.

The primary endpoint was change from baseline to Week 6 in the PANSS total score, reported as a mean on a scale measured in units. The Positive and Negative Syndrome Scale is a 30-item rating scale for positive symptoms, negative symptoms, and general psychopathology in people with schizophrenia. Ratings draw on a structured clinical interview with the patient and supporting clinical information from family, hospital staff, or other reliable informants.

Each item is rated from 1, meaning absent, to 7, meaning extreme. The total score can range from 30 to 210, and a higher score indicates worse symptoms. A negative change score indicates improvement. These properties make change in the total score a way to describe the direction and magnitude of symptom-score movement over the trial interval. The outcome is a continuous measure: it can take values across a scale rather than representing only a yes-or-no event.

Change from baseline uses each participant’s starting score as the reference for describing the later score. Comparing average changes between groups can help distinguish observed group-level movement from change within one group alone. This is a general statistical explanation, not a claim about the trial’s analysis details. The registry record identifies the mean and standard error as the reported summary format, but numerical primary-outcome results are not reported in the registry record. The listed secondary outcome was change from baseline to Week 6 in the CGI-S score; its numerical results are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous primary outcome summarized as a mean, with standard error as the dispersion measure. It describes the outcome interval and the population used for the primary efficacy parameter. It does not report the analysis model, treatment contrasts, confidence intervals, hypothesis tests, missing-data procedure, or multiplicity strategy. The explanations below describe general statistical concepts; they should not be taken as a description of methods used in this trial unless those methods are explicitly reported.

What does a mean change describe?

For a continuous outcome, a mean summarizes the central level of the observed values. For a change outcome, each value represents movement from baseline to the specified follow-up. A group mean change describes the average movement for the participants included in that analysis. It does not show how much individual participants varied, and it does not mean that every participant had a change equal to the average.

In this trial, negative PANSS change is defined as improvement. A group mean alone would not tell whether a between-group difference was statistically distinguishable from chance variation. That requires a comparison estimate together with information about its uncertainty and the analysis used to obtain it. Such numerical primary-outcome results are not reported in the registry record.

What does a standard error convey?

General explanation: a standard error describes the estimated uncertainty in a statistic, such as a sample mean. It is not the same as the spread of individual participant scores. A standard deviation describes variation among observations, whereas a standard error concerns how precisely a statistic has been estimated. A standard error can contribute to a confidence interval or a test statistic when the relevant method and assumptions are specified.

The registry names standard error as the dispersion measure for the primary outcome, but the numerical values are not reported in the registry record. There is therefore no basis in the posted information for judging the precision of a group mean or calculating a comparison interval.

Why is the treatment contrast important?

General explanation: a treatment contrast expresses the estimated difference between groups for an outcome. For a change score, it would compare the average change in one group with the average change in another. The direction of the contrast depends on the order in which groups are subtracted, so interpretation requires a clear statement of that order. A contrast is more informative for a comparative question than separate within-group changes alone, because each group may change over time for reasons unrelated to the treatment contrast.

The registry lists several treatment groups, but a single numerical primary-outcome contrast is not reported in the registry record. The record also does not identify a preferred comparison or explain how comparisons among the groups were selected. No contrast should be inferred from the treatment names or from the safety counts.

What does a confidence interval add?

General explanation: a confidence interval combines an estimate with an indication of its statistical uncertainty under a specified procedure. A narrow interval indicates greater precision than a wide interval, all else equal. An interval can also show which effect sizes remain compatible with the observed data and the assumptions used in the analysis. It does not assign a probability to the true value after the interval has been calculated, and its interpretation depends on the method and assumptions.

No primary-outcome confidence interval is reported in the registry record. Consequently, the data available in the record do not show how precisely any group difference was estimated. A p-value, if reported, would not replace an effect estimate and an interval because it does not describe the size of the effect or the full range of uncertainty.

Why can over-dispersion matter?

General explanation: over-dispersion arises when observed variability is greater than a statistical model expects. If a model assumes less variability than is present, uncertainty can be understated and statistical evidence can appear stronger than warranted. Model choice should reflect the outcome’s distribution and the way observations were collected. This is a general consideration for statistical analysis, not a documented feature of this trial. The primary endpoint is a continuous score, and the registry record does not report a model or describe over-dispersion.

How should planning illustrations be read?

General explanation: a sample-size illustration estimates the number of participants that might be required under stated assumptions, such as an effect to detect, a significance level, allocation, and an approximation method. It is a planning calculation, not a measure of the probability that a completed trial found an effect. It must not be described as observed power. The record’s stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Those assumptions are not reported as the trial’s original design rationale, and a sample-size justification is not reported in the registry record.

The record does not report enough primary-outcome results to interpret a trial-specific estimate or its precision. General statistical explanations can clarify what information would be needed, but they cannot fill in missing estimates, analysis choices, or protocol details.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary PANSS outcome and a secondary CGI-S outcome, and it includes multiple treatment groups. This raises general questions about multiplicity: when several outcomes, doses, or pairwise comparisons are tested, the chance of at least one apparently unusual result can increase if each test is interpreted independently. Statistical plans may address this in different ways, but the appropriate approach depends on the questions and analysis plan.

The registry record does not report a multiplicity adjustment, a hierarchy of outcomes or comparisons, or which treatment contrasts were designated as primary. It is therefore not possible to determine from the record how the investigators handled the number of potential comparisons. The outcome counts in the record do not, by themselves, reveal the testing strategy.

The primary-outcome population includes participants who took at least 1 dose of double-blind investigational product and had at least 1 post-baseline PANSS total-score assessment. This is the population definition stated for that endpoint. The record does not report how many participants met it in each group or how participants without a post-baseline assessment were handled. Details of missing-data procedures, including imputation or model-based approaches, are not reported in the registry record.

The term intent-to-treat appears in the stated population definition, but the criteria are exposure to at least 1 dose and availability of at least 1 post-baseline primary assessment. The record does not provide further information about analysis populations for other outcomes. These limits make it important to distinguish the enrollment figure from the population contributing to a particular analysis. The registry record does not report group-specific primary-outcome denominators or a flow of participants through the analysis population.

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: psychotic behaviour (2.0%), blood creatine phosphokinase increased (0.7%), chest pain (0.7%), psychotic disorder (0.7%), schizophrenia (0.7%).

The safety record gives, for each treatment group, the number at risk and the number affected by serious adverse events, other adverse events, and deaths. These are descriptive counts. They should be read with their group-specific at-risk counts, and not treated as estimates of causal effects. The record does not provide a statistical comparison of safety outcomes or explain how events were attributed to treatment.

For placebo, 151 participants were at risk for serious events and 7 were affected; 151 were at risk for other events and 67 were affected; deaths were 0. For cariprazine 1.5 mg, the corresponding figures were 145 at risk and 5 affected for serious events, 145 at risk and 73 affected for other events, and 0 deaths. For cariprazine 3.0 mg, they were 146 at risk and 0 affected for serious events, 146 at risk and 74 affected for other events, and 0 deaths.

For cariprazine 4.5 mg, 147 participants were at risk for serious events and 4 were affected; 147 were at risk for other events and 87 were affected; deaths were 0. For risperidone 4.0 mg, the corresponding figures were 140 at risk and 3 affected for serious events, 140 at risk and 80 affected for other events, and 0 deaths. The registry lists serious-event terms including psychotic behaviour at 2.0%, and blood creatine phosphokinase increased, chest pain, psychotic disorder, schizophrenia, and atrioventricular block second degree, each at 0.7%.

These counts do not indicate event severity beyond the registry’s serious-versus-other classification, timing, duration, or individual clinical course. Those details are not reported in the registry record.

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

The record establishes that a randomized, double-blind, parallel-group phase 2 study evaluated cariprazine in adults with acute exacerbation of schizophrenia, with placebo and risperidone groups also listed. It defines a primary symptom outcome, describes the scale and its direction, and identifies the analysis population for that outcome. It also reports selected adverse-event counts. These details characterize the study question and some of the information recorded about safety.

They do not establish the size or direction of a comparative primary-outcome effect. Numerical PANSS results for a single treatment comparison are not reported in the registry record, and the numerical CGI-S results are not reported either. As a result, the record does not support a claim that one treatment group had a greater or smaller average symptom change than another. It also does not show how precise a possible difference was or whether it would meet any statistical or clinical threshold.

General interpretation of treatment effects distinguishes statistical evidence from clinical importance. A small estimate can be statistically precise without being important to patients, while a potentially important estimate can be uncertain. Judging either requires the effect estimate, its uncertainty, relevant clinical context, and a prespecified interpretation framework. Those numerical outcome results and contextual details are not reported in the registry record, so no such judgment can be made from this record alone.

The adverse-event counts likewise do not prove that a treatment caused or prevented an event. They are counts within the recorded groups, without the comparative analysis or event-level details needed for causal interpretation. The absence of recorded deaths in the listed groups describes the posted death counts; it does not establish the absence of all safety concerns.

Accordingly, the registry information supports a careful account of design, endpoint definitions, and reported safety counts. It does not support a conclusion about comparative efficacy, the precision of the primary effect, or an overall benefit-risk judgment.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a defined endpoint and a reported treatment contrast are both necessary. The registry specifies a continuous primary outcome, its time interval, its measurement scale, and the direction in which change is interpreted. Those details make the endpoint understandable and establish what a numerical result would mean.

At the same time, the record identifies three cariprazine dose groups, placebo, and risperidone. Multiple groups create several possible comparative questions. A reader needs to know which comparisons were planned, what estimates were obtained, and how uncertainty and multiplicity were handled. The registry record does not report those analysis details or a single numerical primary-outcome comparison. This illustrates the difference between trial registration information and a complete statistical account of results.

The endpoint’s mean and standard error are named as summary measures, but neither is enough on its own to answer a comparative question. A treatment contrast and an uncertainty interval would be needed to assess the direction, size, and precision of a difference. Their absence from the registry record limits statistical interpretation even though the trial design and outcome are described.

The safety information also illustrates the value of separating descriptive counts from causal claims. Group-specific counts can show what was recorded, but without an analysis plan and comparative estimates they do not establish that treatment caused a difference. The primary endpoint, secondary outcome, and safety summaries each answer different questions and should not be treated as interchangeable.

These distinctions matter for researchers reading registry records: a clear description of what was intended and measured is useful, but it cannot replace reported estimates, uncertainty, and analysis methods. Statistical transparency depends on both design information and interpretable results.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific limitations in the available record restrict interpretation. The central limitation is that numerical primary-outcome results for a single comparison are not reported in the registry record. The record names mean change in PANSS total score and standard error, but does not give group means, a treatment contrast, or an interval. Numerical results for the secondary CGI-S outcome are not reported either.

The record lists multiple treatment groups but does not report the allocation ratio, group sizes for the primary-outcome analysis, or the specific comparisons designated for inference. Enrollment is reported as 732, but that figure does not identify the analysis population for each outcome. Although the primary population is defined by treatment exposure and availability of at least 1 post-baseline PANSS assessment, the record does not report how missing assessments were handled or how many participants contributed to each group’s analysis.

Details that would clarify the risk of bias and the interpretation of estimates are also not reported in the registry record. These include the allocation-generation and concealment procedures, which parties were masked, the statistical model, the approach to multiplicity, and the original sample-size justification. The registry’s stated planning-illustration assumptions should not be read as the trial’s design rationale.

The safety record reports counts but does not describe event timing, duration, attribution, or statistical comparisons. The list of serious-event terms does not provide enough detail to characterize each event or its clinical course. These limits mean the record is useful for describing the study and selected counts, but not for a complete evaluation of efficacy, precision, missing-data sensitivity, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Cariprazine (RGH-188) in the Acute Exacerbation of Schizophrenia — NCT00694707.
• Registry record last updated 2019-06-12; status last verified 2019-05.
• Results first posted 2019-06-12.
• 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

The registry describes a completed phase 2 randomized, double-blind, parallel-group study sponsored by Forest Laboratories. It enrolled 732 adults with acute exacerbation of schizophrenia and compared placebo with cariprazine at 1.5 mg, 3.0 mg, and 4.5 mg; risperidone 4.0 mg was also included. Each listed regimen was taken orally once a day for 6 weeks.

The primary outcome was change from baseline to Week 6 in PANSS total score, with negative change indicating improvement. Change in CGI-S score was listed as a secondary outcome. Numerical outcome results for a single primary comparison and for the secondary outcome are not reported in the registry record. Serious and other adverse-event counts, death counts, and selected serious-event terms are reported, but these descriptive data do not establish comparative treatment effects.