Study of Amantadine for Risperidone Consta or Paliperidone Treated Patients to Decrease Prolactin Elevation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Amantadine for Risperidone Consta or Paliperidone Treated Patients to Decrease Prolactin Elevation (NCT00975611), a randomized phase 4 study. The primary outcome is Change in Prolactin Levels for Individuals Treated With Adjunctive Amantadine Versus Placebo..

2. Clinical Question

3. Trial Design

This was a Phase 4 randomized, quadruple-masked, parallel-group study. The registry lists three regimens: amantadine 100mg twice per day, amantadine 200mg twice per day, and placebo twice per day. It describes the primary question as adjunctive amantadine versus placebo, but does not report the allocation details or the planned statistical comparison for the two amantadine doses. The masking roles and procedures are not reported in the registry record.

The study concerned people with schizophrenia or schizoaffective disorder who were being treated with paliperidone ER or risperidone Consta. The primary outcome was change in prolactin levels, assessed at week 4 and week 8. The registry lists enrollment as 6 and status as terminated. Its primary-outcome description says 22 subjects consented; 15 screen-failed because prolactin levels did not meet eligibility criteria, while 1 screen-failed because of a positive drug screen. It attributes termination to this unanticipated high screen-failure rate. These figures describe different entries in the record, and the relationship between listed enrollment and the consented and screened subjects is not explained.

The start is recorded as 2009-10 and primary completion as 2012-01. No outcome analyses are listed. The reason for termination is described, but further operational details, such as how much treatment participants received or whether follow-up was completed, are not reported in the registry record. A sample-size justification and a detailed statistical analysis plan are also not reported in the registry 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: Of the 22 consented subjects, 15 screen-failed because prolactin levels did not meet eligibility criteria, and 1 screen failed due to a positive drug screen.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the 22 consented subjects, 15 screen-failed because prolactin levels did not meet eligibility criteria and 1 screen-failed due to a positive drug screen. Because of this unanticipated high screen-failure rate, the study was terminated. Only baseline characteristics of all 22 consented/screened subjects were published and are reported here.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Change in Prolactin Levels for Individuals Treated With Adjunctive Amantadine Versus Placebo., measured over week 4 and week 8.

The primary endpoint is change in prolactin levels for individuals treated with adjunctive amantadine versus placebo. Prolactin is the hormone targeted by the study: the registry describes elevated prolactin as a possible side effect associated with paliperidone ER or risperidone Consta. Assessing change focuses the question on whether levels differ over time from baseline, rather than only on the level at a single assessment. The specified assessment times are week 4 and week 8.

The registry record does not state the measurement unit, the exact change calculation, or whether the planned comparison was based on change at each time separately or on a joint analysis over time. It also does not report baseline or follow-up prolactin values, an estimated treatment effect, a confidence interval, or a p-value. Thus, the endpoint is identifiable from its title and timeframe, but its numerical results and analysis details are not reported in the registry record.

The study summary also mentions reducing side effects and improving psychiatric symptoms as goals. These are not described as the primary endpoint, and their outcome definitions or results are not reported in the registry record. The primary prolactin measure can address the stated hormone-level question only; it does not by itself quantify changes in symptoms or other side effects.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to make treatment groups comparable on average by assigning participants through a chance process. That can reduce systematic differences between groups at the start of a trial, though it cannot guarantee balance in a small study. The record identifies the design as randomized but does not report the randomization sequence, allocation concealment, or group assignment counts. Therefore, the method of assignment and the realized balance between groups cannot be assessed from the registry record.

A parallel-group design assigns participants to a regimen that is followed alongside the other groups over the study period. Here, the listed regimens were amantadine 100mg twice per day, amantadine 200mg twice per day, and placebo twice per day. The registry describes the primary question as adjunctive amantadine versus placebo. It does not specify whether the two active regimens were to be analyzed separately, combined, or compared with each other. The exact contrast used for the primary analysis is therefore not reported in the registry record.

Quadruple masking indicates that masking was part of the design, but the record does not identify which participant, care, or assessment roles were masked, or how masking was maintained. In general, masking can limit the influence of expectations on treatment delivery, reporting, and outcome assessment. It does not remove bias automatically, and it cannot substitute for a defined analysis or complete outcome data. Details needed to assess those protections are not reported in the registry record.

The primary endpoint is change in prolactin levels, with assessments specified at week 4 and week 8. In general, change from baseline is calculated by comparing a participant's follow-up measurement with that participant's baseline measurement. A treatment comparison can then estimate whether changes differ between groups. The registry does not specify the exact calculation, the baseline measurement schedule, the units, or the model used. It also does not report whether the two follow-up times were intended as separate endpoints or as repeated observations in a single model.

For continuous outcomes, an analysis might report a difference in average change between groups, with a confidence interval describing uncertainty. That is a general explanation, not a description of the analysis used in this study: no primary analysis is listed. Without the participant-level data, group summaries, or a reported estimate, it is not possible to reconstruct the intended treatment contrast. The record's outcome title alone does not establish whether the analysis would have adjusted for baseline values or other characteristics.

General statistical methods also rely on assumptions about the outcome distribution, the relationship between repeated measurements, and the handling of missing observations. The registry does not report a statistical model, distributional assumptions, missing-data method, or analysis population. If prolactin measurements were skewed or unusually variable, a method suited to those features might be considered in a complete analysis; whether that was relevant or planned for this study is not reported in the registry record. No assumption should be attributed to the investigators without a recorded analysis plan.

There are no listed analyses for the primary outcome. Accordingly, no standard error, confidence interval, p-value, or adjusted estimate is available to interpret. General explanations of these quantities cannot supply a missing study result. They describe how uncertainty could be communicated if an analysis were reported, not what the effect was in this trial.

The record includes wording for a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not give an observed effect or sample-size illustration values. A planning calculation is not an observed treatment result, and a sample-size target cannot be treated as evidence that a study had a particular probability of detecting an effect. The record does not report the trial's own sample-size justification or the assumptions behind its original design.

For interpretation, the most important methodological fact is not the choice among possible statistical models but the absence of a reported analysis. The clinical question is clear enough to identify the intended outcome and groups, yet the registry record does not contain the estimates needed to judge effect size or precision. The design labels describe how the trial was intended to operate; they do not provide evidence about the outcome.

10. Multiplicity, Missing Data and Analysis Populations

The study lists two active amantadine regimens, a placebo regimen, two primary assessment times, and additional stated goals concerning side effects and psychiatric symptoms. Considering multiple doses, time points, or outcomes can create multiplicity: when many comparisons are examined, the chance of a seemingly notable result can increase. In general, a statistical plan may define a primary contrast, a hierarchy of outcomes, or an adjustment method to address that issue. Such a plan is not reported in the registry record, and no multiplicity procedure is listed.

No primary outcome analysis is reported, so there are no estimates or p-values to assess for multiplicity. The record does not report whether week 4 and week 8 were to be treated as separate tests, whether either time point had priority, or how the two amantadine doses were to be compared with placebo. It also does not report a statistical testing strategy for the other study goals.

Missing-data methods and analysis populations are likewise not described. The record does not say whether analyses were planned for all randomized participants, participants who started treatment, or another defined group. Nor does it report how missing prolactin measurements, treatment discontinuation, or incomplete follow-up would have been handled. The screening failures are described, but they are not a substitute for an account of missing outcome data among randomized participants.

Because the trial was terminated and outcome analyses are absent, the record does not support an assessment of whether missingness affected the results or whether a planned analysis was completed. These details are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event entry labels its group “All Consented Subjects” and reports 6 at risk for serious adverse events, with 0 affected. It also reports 6 at risk for other adverse events, with 0 affected. The death entry is null, which is not the same as a reported count of zero. These figures should be read as the registry's recorded safety counts, not as a complete account of risk across all consented or screened subjects.

The primary-outcome description says 22 subjects consented and details screening failures; the adverse-event entry lists 6 at risk. The registry does not explain the relationship between these counts or specify the safety observation period. It also does not provide event descriptions or group-specific safety results by amantadine dose and placebo. Thus, the recorded zero affected in the listed group does not establish that no events occurred among every person who consented or was screened, nor does it permit comparison between regimens.

Safety counts depend on who was included, what events were captured, and how long participants were observed. Those details are not reported in the registry record. The posted figures therefore provide limited information about the recorded group and should not be treated as a complete estimate of safety.

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

The record establishes that investigators planned a randomized, masked comparison of adjunctive amantadine regimens with placebo in people treated with paliperidone ER or risperidone Consta. The primary question concerned change in prolactin levels at week 4 and week 8. It also records that the study was terminated after a high screen-failure rate, with 15 consented subjects failing prolactin eligibility criteria and 1 failing because of a positive drug screen.

What the record does not establish is whether amantadine changed prolactin levels, whether either dose differed from placebo, or whether any observed difference was precise or clinically meaningful. No outcome values or analyses are reported. The record also cannot establish that the regimens were equivalent, that they had no effect, or that one dose was preferable. Those interpretations require estimates and uncertainty information that are absent.

The stated goals concerning side effects and psychiatric symptoms should also be distinguished from the reported primary endpoint. Those goals do not constitute numerical findings, and their outcome definitions and analyses are not available in the registry record. Similarly, the listed safety counts apply to the group and at-risk numbers recorded in the adverse-event entry; they do not provide a full comparison of harms among treatment groups.

In general, a terminated study may leave its intended treatment question unanswered, particularly when no outcome analysis is posted. That is the statistical situation in this record: the design and intended endpoint are described, but treatment effects cannot be estimated from the information recorded. This is not evidence that the treatment worked or did not work. It is a limit on what can be concluded from the registry record.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical research between a clearly stated question and an answer supported by data. The registry identifies a population, two adjunctive amantadine regimens, a placebo regimen, and a primary outcome focused on prolactin change. Yet no primary analysis is reported. Knowing the intended design cannot replace the results needed to estimate a treatment effect.

The record also shows why recruitment and eligibility information matters to interpretation. It attributes termination to an unanticipated high screen-failure rate, including failures related to prolactin eligibility. That information helps explain why the study did not proceed as intended, while leaving the treatment comparison unresolved. It also cautions against interpreting listed enrollment as though it were automatically the number analyzed or the number randomized; those counts are not explained in the registry record.

Statistically, the absence of an estimate and uncertainty interval is consequential. Without those, readers cannot assess the size, direction, or precision of any difference, nor determine how results may have varied across assessment times or doses. General methods such as confidence intervals and multiplicity adjustments matter only when the analysis and its results are available to evaluate.

The record is therefore useful for understanding the intended question and the reason recorded for termination, but it cannot support a conclusion about the primary outcome. This distinction is central to responsible interpretation: a trial's planned comparison, its conduct, and its reported statistical evidence are separate elements.

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 main trial-specific limitation is that the registry record contains no primary-outcome analysis. It does not report prolactin values, changes, effect estimates, confidence intervals, or p-values at week 4 or week 8. The treatment comparison therefore cannot be quantified or evaluated for precision.

The study was terminated after a high screen-failure rate. The record reports that 15 of 22 consented subjects failed because prolactin levels did not meet eligibility criteria and 1 failed due to a positive drug screen. It lists enrollment as 6, while the adverse-event entry lists 6 at risk. The relation among these counts, the number randomized, and the number with outcome measurements is not reported in the registry record.

The precise primary comparison is also unclear. Three regimens are listed, while the outcome title describes adjunctive amantadine versus placebo. The record does not say whether each dose was compared separately with placebo or whether another contrast was planned. Units, the exact change calculation, analysis model, analysis population, and missing-data handling are not reported.

Although the summary mentions side effects and psychiatric symptoms, their definitions and results are not provided. Safety information is limited to the recorded at-risk and affected counts, with no treatment-group breakdown or observation-period details. These omissions limit interpretation of both effectiveness and safety. The registry does not report a detailed statistical analysis plan or the study's sample-size justification.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Amantadine for Risperidone Consta or Paliperidone Treated Patients to Decrease Prolactin Elevation — NCT00975611.
• Registry record last updated 2013-06-10; status last verified 2013-01.
• Results first posted 2013-06-10.
• 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

NCT00975611 is a Phase 4 randomized, quadruple-masked, parallel-group study of adjunctive amantadine for people treated with paliperidone ER or risperidone Consta. The listed regimens are amantadine 100mg twice per day, amantadine 200mg twice per day, and placebo twice per day. The primary outcome is change in prolactin levels at week 4 and week 8.

The record lists enrollment as 6 and status as terminated. It says 22 subjects consented, with 15 failing screening because prolactin levels did not meet eligibility criteria and 1 because of a positive drug screen; termination is attributed to the high screen-failure rate. No primary analyses or numerical outcome results are reported. Safety entries list 6 at risk and 0 affected for serious adverse events, and 6 at risk and 0 affected for other adverse events; deaths are recorded as null.

The registry record describes the intended study question and termination, but does not provide evidence to estimate the effect of amantadine on prolactin levels.