Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia (NCT01009060), a randomized phase 2 study. The primary outcome is Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512.

2. Clinical Question

The clinical question centers on cognitive performance, rather than a single symptom rating. The primary endpoint combines performance across tasks in the computerized CSSB, with higher composite scores representing better performance. Secondary outcomes include a composite measure from the MCCB, individual cognitive-domain scores, psychiatric and negative-symptom scales, a performance-based skills assessment, and adverse-event outcomes.

This distinction matters when interpreting the trial’s aims: the registry names cognitive enhancement as the focus, but the listed outcomes span several domains. The registry entries identify the comparison and measurement schedule, but do not establish the size, direction, or precision of any treatment contrast. They also do not report whether the observed primary outcome favored either group.

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 2 study sponsored by GlaxoSmithKline. The registry lists schizophrenia as the condition and describes the participants as stable patients with schizophrenia. The study compared repeat dosing of GSK239512 with repeat dosing of matching placebo. The record reports enrollment of 50.

In a parallel-group design, each participant is assigned to one intervention group rather than moving between treatments. Random allocation is intended to support a fair comparison by limiting systematic differences between groups at the outset. The registry states that allocation was randomized, but the specific randomization procedure, allocation concealment method, and stratification factors are not reported in the registry record.

The study is described as triple-masked. The record does not specify which three parties were masked, how masking was maintained, or whether masking was assessed. These details should not be inferred from the label alone. The study status is completed; its listed start date is 2009-12-01 and its primary completion date is 2011-08-10.

The primary outcome was change from baseline in the composite score of the computerized CSSB, measured at baseline and up to Week 7. The registry also lists cognitive, psychiatric, functional-skill, and safety outcomes. The primary outcome population is identified as the ITT Population, but only participants available at the specified time points were analyzed. Participants recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6, and the record notes lower participant counts at those visits.

The record does not report the dosing schedule in more detail, treatment duration beyond the endpoint timeframe, the number randomized to each group in the main outcome analysis, or a statistical analysis plan. The safety information lists 25 at risk in each group; that safety denominator should not automatically be treated as the denominator for every efficacy analysis.

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: A total of 118 participants (par.) were screened. Out of these 50 participants were randomized. Out of these, safety population consisted of 50 participants and intent-to-treat (ITT) population consisted of 46 participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population. Only those participants available at the specified time points were analyzed. Par. recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6 and hence the number of par. at these visits are lower.

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: Baseline characteristic data is presented for ITT population which consisted of all participants randomized to treatment, who had taken at least one dose of investigational product and who had at least one post-Baseline CogState Schizophrenia Battery (CSSB) assessment during the on-treatment phase.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512, measured over Baseline and up to Week 7.

The primary endpoint is change from baseline in the composite score of the computerized CSSB following dosing with GSK239512. The CSSB assesses verbal memory, working memory, motor speed, verbal fluency, attention and speed of information processing, and executive functions. Higher scores on the component measures represent better performance.

The composite was constructed by averaging the measures and then calculating a z-score. In general, a z-score expresses a measure’s position relative to a reference mean in standard-deviation units. The registry describes the composite score as oriented so that a higher value represents better performance. The endpoint is therefore intended to capture performance across a set of cognitive tasks rather than to stand for any single task or domain.

Baseline was defined using the average of two CSSB tests: one on the day before dosing began and another before dosing on Day 1. Change from baseline was calculated as the score at a given time minus the baseline score. For individual CSSB tasks, the baseline used the mean of the second screening assessment and the Day 1 pre-dose assessment. The timeframe is baseline and up to Week 7.

A composite can offer a broad summary when an intervention is being evaluated across related cognitive functions. It can also conceal differences between domains: a composite change does not by itself show whether every task moved in the same direction. The registry record does not report the primary composite estimates, their uncertainty, or the corresponding comparison with placebo in the information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-group comparison and a continuous primary outcome summarized as a least-squares mean with a standard error. The endpoint is change in a composite CSSB score. These labels identify the broad form of the analysis, but the detailed model specification, covariates, handling of repeated measurements, and missing-data method are not reported in the registry record.

What does a least-squares mean represent?

In general, a least-squares mean is a model-based group mean. Unlike a simple arithmetic average, it can reflect adjustments for variables included in the statistical model. The registry identifies the primary outcome parameter as a least-squares mean, but does not identify the adjustment variables or model formula. It is therefore not possible to determine from the record whether the reported estimate, if consulted elsewhere in the registry, is adjusted for baseline score or other factors.

The primary endpoint is a change score, calculated by subtracting baseline from the score at a given time. Change scores can describe movement relative to a participant’s starting value. Interpretation depends on the exact model and the participants contributing data at each time point. The record says that only participants available at the specified time points were analyzed, but does not give the number contributing to each primary comparison in the information.

How should a standard error be read?

In general, a standard error describes the statistical uncertainty of an estimated quantity, such as a group mean. It reflects how precisely the estimate is determined under the analysis assumptions. It is not the same as the spread of individual participant scores: a group can have substantial variation among participants while its estimated mean has a different degree of uncertainty. A standard error alone is not a confidence interval and does not show the full range of values compatible with the data. The primary estimate and standard error are not reported in the information.

What does randomization contribute?

In general, random assignment helps make groups comparable on average at the start of a study, including on factors that were not measured. It does not guarantee identical groups in a particular trial, especially when the study is limited in size. A valid comparison also depends on how participants are analyzed, how missing outcomes are handled, and whether the reported model matches the trial design. The registry confirms randomized allocation, but does not report the specific procedure or analysis details needed to assess these matters.

Why is the composite score relevant?

The CSSB composite brings together performance across multiple cognitive tasks, then expresses the averaged composite as a z-score. In general, combining related measures can give a broader summary than relying on a single task. It can also make the result harder to interpret clinically if the contributing domains differ in their patterns. The record explains that higher composite scores represent better performance, but it does not provide the observed composite changes or domain-level results in the information.

What can planning calculations tell readers?

The study information includes a sample-size planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between the groups, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are hypothetical planning scenarios: they ask how many participants per arm would be needed under specified assumptions to detect a chosen effect at a chosen power level. They are not observed power for this completed trial, do not replace the trial’s results, and do not establish that the assumed effect is the true effect.

Planning illustrations also depend on their assumptions. In general, changing the target effect, variability, allocation, significance threshold, or model assumptions changes the planning result. The sample-size section should therefore be read as a set of conditional scenarios, not as evidence that the original study was designed around those calculations. The registry record does not report its own sample-size justification or design assumptions in the information.

Why should the analysis population be checked?

The record identifies the ITT Population for the primary outcome, while also stating that only participants available at a specified time point were analyzed. These descriptions do not fully explain the analysis set or missing-data procedure. In general, an intention-to-treat approach aims to retain participants in their randomized groups, while analyses limited to observed outcomes can be affected if availability is related to treatment or outcome. The registry does not describe imputation, a likelihood-based method, or sensitivity analyses, so no particular approach should be assumed.

For safety outcomes, counts of participants affected are descriptive summaries. They are not a model-based estimate of the primary cognitive effect. When serious events are sparse, differences in counts can be highly uncertain; the absence of a recorded event in a group does not establish that the underlying risk is zero. These general principles apply when reading the posted safety figures, without changing what the counts themselves report.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 26 analyses. Its secondary outcomes cover additional cognitive measures and domains, psychiatric and negative-symptom scales, functional skills, and adverse events. Testing or estimating multiple outcomes can be useful for describing a trial’s breadth, but it also raises multiplicity concerns. In general, the more comparisons considered, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified hierarchy is used.

The registry record does not report a multiplicity strategy, such as a hierarchy among outcomes, an adjustment procedure, or a distinction between confirmatory and exploratory comparisons. It also does not report whether the primary endpoint had a prespecified single contrast or how the multiple time points were treated statistically. Those details are not reported in the registry record, so the listed number of analyses should not be taken as evidence that any particular correction was applied.

For missing data, the primary outcome population is identified as the ITT Population, but the record says only participants available at specified time points were analyzed. It notes that participants recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6, and that participant counts at those visits are lower. The record does not explain the reasons for unavailability beyond that visit schedule, give outcome-specific missingness counts, or describe a missing-data model or sensitivity analysis.

In general, missing outcome data can affect interpretation when the probability of having a measurement is related to treatment or to the outcome itself. The registry entries do not establish whether that occurred. They also do not fully specify how the ITT label was implemented for each analysis. The analysis population and missing-data assumptions should therefore be treated as incompletely documented in the registry record.

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: stress (4.0%).

The registry reports serious adverse events by group as numbers of participants affected and numbers at risk. In the placebo group, 1 participant was affected among 25 at risk; in the GSK239512 group, 0 participants were affected among 25 at risk. The record lists 0 deaths in each group. These are observed counts during the study, not estimates of a precisely known underlying risk.

The record also lists the top serious adverse-event term as Stress, with 4.0%. That entry should be read as the registry’s reported term and percentage; the information does not provide further detail about its definition, timing, severity, or participant-level context. The other adverse-event counts list 11 participants affected in the placebo group and 15 in the GSK239512 group, with 25 at risk in each group. These are listed separately from serious adverse events.

In general, serious and non-serious adverse events are distinct categories, and a participant may contribute to more than one event category or term. Counts alone do not establish whether an event was caused by treatment. With sparse serious-event counts, the observed difference is especially imprecise, and a zero count in a group does not demonstrate absence of risk. The registry information does not report an inferential safety comparison or detailed event narratives.

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

The trial asks a focused statistical question: how the CSSB cognitive composite changed from baseline after repeat dosing with GSK239512, relative to matching placebo, over baseline and up to Week 7. The endpoint’s construction and direction are described, and the record identifies the design as randomized, triple-masked, and parallel-group. Those features explain what was intended to be compared, not what the comparison found.

The primary group estimates and treatment contrast are not reported in the information. Thus, neither the direction nor magnitude of the primary result can be stated, and its precision cannot be assessed. The lack of a reported estimate in the registry record is not evidence that the groups were equal, nor does it establish a benefit or lack of benefit. It means that the primary result cannot be interpreted from the registry information available in this record summary.

Even when estimates are available, a difference in a composite score is a statistical description of performance on the specified battery. It does not automatically establish a meaningful change in daily functioning, a change in every cognitive domain, or a lasting effect. This trial’s listed secondary outcomes include a functional-skills assessment, but no results for that measure are reported in the information. The registry also does not report a threshold for interpreting a change as clinically important.

The safety counts provide a limited descriptive account of affected participants during the study. They should not be read as proof that either intervention is free from serious adverse events, or as a definitive comparison of safety. The same caution applies to any single event term or sparse count: its interpretation depends on definitions, follow-up, and broader evidence not reported.

Accordingly, the posted information supports describing the trial’s question, outcome construction, design, and recorded safety counts. It does not support a clinical recommendation or a claim that GSK239512 did or did not improve cognition. Statistical interpretation requires the actual estimates, their uncertainty, the analysis details, and context for the outcome’s importance.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a cognitive composite endpoint with a randomized parallel-group comparison and multiple additional outcomes. A composite can summarize performance across related tasks, but its meaning depends on how its components are combined and how the resulting score is interpreted. The registry explains the CSSB domains, baseline construction, and direction of the composite, which are essential context for understanding any reported change.

The record also illustrates why a design label is only part of an analysis description. Randomization and masking are relevant safeguards, but interpretation further depends on the model, the analysis population, outcome availability, and uncertainty. Here, the record names the ITT Population while also describing analyses of participants available at specified time points. It notes that some visits were not assessed for participants recruited under protocol amendment 2. These details make clear why visit-specific analysis denominators and missing-data methods matter.

The breadth of outcomes is another statistical consideration. Cognitive, psychiatric, functional, and safety outcomes may illuminate different aspects of a study, but a large outcome set calls for clear reporting of the primary comparison and multiplicity approach. The registry lists 15 outcome measures and 26 analyses, yet the multiplicity strategy is not reported in the registry record. A reader cannot determine from the listed outcomes alone which comparisons were confirmatory or how the risk of chance findings was managed.

Finally, sparse safety counts show why descriptive observations should not be overstated. Counts are important for transparency, but small numbers do not establish precise comparative risks. In this record, the primary efficacy estimates are not reported in the information, so design and measurement details can be examined while the central treatment comparison remains unresolved.

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 registry information does not include the primary outcome estimates, their standard errors, confidence intervals, or p-values. It therefore cannot establish the size, direction, or precision of the CSSB comparison. The registry entries also do not report the secondary outcome results, despite the broad outcome list.

Important analysis details are not reported in the registry record. These include the model specification, covariates, handling of repeated observations, missing-data method, and any sensitivity analyses. The record does not explain the randomization procedure or specify which parties were masked under the triple-masking description. It also does not state how multiplicity was handled across the listed outcomes and analyses.

The primary outcome population is described as ITT, while analyses are limited to participants available at specified time points. The record notes that participants recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6, leading to lower participant counts at those visits. Outcome-specific denominators and the consequences of missing measurements are not reported in the information.

Generalizability is also difficult to assess from the available description. The record identifies stable patients with schizophrenia, but further eligibility criteria, participant characteristics, and details of the treatment regimen are not reported. The safety counts are descriptive and sparse; the record does not provide detailed event narratives or an inferential comparison. These limitations constrain interpretation without determining what the full trial report might contain.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia — NCT01009060.
• Registry record last updated 2017-11-08; status last verified 2017-08.
• Results first posted 2017-09-27.
• 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

NCT01009060 is a completed randomized, triple-masked, parallel-group Phase 2 study sponsored by GlaxoSmithKline. It evaluated repeat dosing with GSK239512 compared with matching placebo in stable patients with schizophrenia. The record lists enrollment of 50, a start date of 2009-12-01, and a primary completion date of 2011-08-10.

The primary outcome is change from baseline in the composite score of the computerized CSSB, measured at baseline and up to Week 7. The primary outcome population is identified as the ITT Population, with only participants available at specified time points analyzed. The record notes that participants recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6.

Safety information lists 1 participant with a serious adverse event in the placebo group and 0 in the GSK239512 group, with 25 at risk in each group; no deaths are listed. The primary efficacy estimates and detailed statistical plan are not reported in the information.