This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Co-Administration of Roluperidone and Olanzapine in Adult Subjects With Moderate to Severe Negative Symptoms of Schizophrenia (NCT06107803), a non-randomized phase 1 study. The primary outcome is Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06107803 |
| Phase | Phase 1 |
| Condition | Negative Symptoms in Schizophrenia |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Minerva Neurosciences |
| Results posted | Yes |
2. Clinical Question
The study concerns adults with moderate to severe negative symptoms of schizophrenia. Its stated aim is to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of roluperidone given with olanzapine. The study first assessed roluperidone as monotherapy, then assessed roluperidone and olanzapine together. Because these treatments were given in sequence to participants rather than compared in randomized groups, the record does not describe a randomized treatment comparison.
Population
Adults with moderate to severe negative symptoms of schizophrenia. The registry lists negative symptoms in schizophrenia as the condition.
Intervention
Roluperidone 64 mg orally each day, first as monotherapy and then with olanzapine 10 mg orally each day during the second treatment phase.
Comparator
There is no randomized or concurrent control group. The study proceeds from roluperidone monotherapy to co-administration; this sequence does not constitute a like-for-like randomized comparison.
Primary question
What safety and pharmacological observations, including the change in AIMS movement score from baseline to the end of the study, are recorded during this treatment sequence?
The primary endpoint focuses specifically on change in the AIMS component movement score from baseline to End of Study on Day 17. The registry describes higher AIMS scores as worse. It also lists pharmacokinetic outcomes for roluperidone and olanzapine, including maximum plasma concentration, time to maximum concentration, and measures of area under the plasma concentration-versus-time curve. The primary endpoint’s numerical result is not reported in the registry record, so the study’s posted information does not show the observed average change or its precision.
3. Trial Design
This is a Phase 1 study with a non-randomized, unmasked, sequential model. The registry labels the study Phase 1, and the official title describes it as Phase 1b. The sponsor is Minerva Neurosciences. The record states that enrollment was 17 and that the study is completed. The listed start date is 2023-10-13, and the primary completion date is 2024-01-12.
Participants were to undergo screening for between 2 and up to 28 days. The summary says eligibility was established during screening and that participants receiving psychotropics would be washed out. Participants remained inpatient at least through the end of Treatment Phase 2. The record does not state whether every enrolled participant completed every planned study period.
Treatment Phase 1 consisted of roluperidone 64 mg orally each day for 7 days on Days 1-7. Treatment Phase 2 consisted of roluperidone 64 mg and olanzapine 10 mg orally at the same time each day for 10 days on Days 8-17. The summary says discharge could occur at least 48 hours after the last administration and collection of the last plasma sample, with the inpatient period subject to extension at the investigator’s discretion.
The sequential structure matters for interpretation. The same study sequence moves from monotherapy to co-administration; allocation was not randomized, masking was absent, and there was no concurrent control arm. Changes observed between phases could reflect the treatment sequence or other time-related factors, and the registry does not describe a design that separates those possibilities. The record does not report a protocol rationale for the sequence, a sample-size justification, or planned interim analyses.
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: Participants underwent three study phases: Screening, Treatment Phase 1 and Treatment Phase 2.
Overall Study
| Stage | Overall Safety Set |
|---|---|
| STARTED | 17 |
| Full Set | 17 |
| Safety Set | 17 |
| Pharmacokinetic Set | 12 |
| Pharmacokinetic Completer Set | 11 |
| COMPLETED | 13 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Overall Safety Set |
|---|---|
| Adverse Event | 1 |
| Withdrawal by Subject | 2 |
| Protocol Violation | 1 |
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.
| Characteristic | Unit | Overall Safety Set |
|---|---|---|
| Participants analysed | 17 | |
| Age, Continuous | Years | 36.3 (SD 8.20) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 17 |
| Body Mass Index at Baseline | kg/m2 | 27.3 (SD 4.58) |
6. Primary Endpoint
The registry lists the primary outcome as Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement, measured over Overall - Change from Baseline to End of Study (Day 17).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline to End of Study on Day 17 in the AIMS component movement score. AIMS is described as a rating scale used to measure tardive dyskinesia. The registry says the scale has 14 items, but the analysis uses items 1 to 10; each of those items is rated from 0 to 4 and the total ranges from 0 to 40. The remaining 4 dental-status items are recorded as yes or no and are not counted in the score. Higher scores imply a worse outcome.
Using a defined scale gives the study a structured way to describe movement symptoms over the treatment period. A change-from-baseline endpoint expresses the end-of-study score in relation to each participant’s starting score, rather than describing the end score alone. The record says the summary was reported for the Safety Set and that the endpoint is expressed as a mean with standard deviation. The actual mean change and standard deviation are not reported in the registry record. Consequently, readers cannot determine the direction or size of the average change, how variable individual changes were, or how precisely the average was estimated from the registry entry.
The endpoint is a safety-related rating outcome within a study also designed to assess pharmacodynamic and pharmacokinetic measures. It should not be treated as a direct measure of every safety outcome or as a complete account of clinical status. The registry’s scale description supports interpretation of the score’s direction and range, but does not supply a clinical threshold for judging the importance of a particular change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the study structure and selected safety counts, but it does not report the numerical result for the primary AIMS change-from-baseline endpoint. It therefore does not show the average change, standard deviation, confidence interval, or a statistical test for that endpoint. A conclusion about the direction, size, or precision of the primary result cannot be drawn from the record. The absence of a posted result is not evidence that the endpoint was unchanged; it means that the endpoint result is not reported in the registry record.
The study enrolled 17 participants overall. The safety figures list 17 participants at risk during Treatment Phase 1 and 15 during Treatment Phase 2. The registry lists 1 serious adverse event in Treatment Phase 1 and 0 in Treatment Phase 2. It lists 5 other adverse events in each phase and 0 deaths in both. Rhabdomyolysis appears among the top serious adverse event terms with a listed value of 5.9%. These counts describe the posted safety record. They do not, by themselves, establish whether an event was caused by study treatment.
Phase-specific counts require care because exposure occurred in sequence, the phase durations differed, and the numbers at risk were not the same. A direct comparison of the counts would not account for those features. The study was non-randomized and unmasked, and it had no like-for-like control comparison. These design characteristics limit what can be attributed to co-administration rather than to the earlier phase, elapsed time, or other factors. The record does not report an adjusted comparison between phases.
The primary endpoint’s stated mean and standard deviation would describe the average change and its variability, but those values are absent. More generally, a mean alone would not describe every participant’s response, and a standard deviation would describe spread rather than the uncertainty around the mean. Confidence intervals and p-values for the primary endpoint are not reported in the registry record. No statistical significance claim can be assessed from the listed endpoint description alone.
The registry lists pharmacokinetic outcomes for both drugs, including Cmax, Tmax, and AUC measures. Their numerical results are not reported in the registry record. As a result, the posted entry does not quantify the pharmacokinetic observations or their precision. The available record supports a description of the planned sequence, endpoint definitions, enrollment, and selected event counts, but not a numerical assessment of the primary endpoint or pharmacokinetic findings.
9. Statistical Methods Explained
The record describes the primary endpoint as a continuous measure summarized by a mean and standard deviation. A continuous outcome can take values across a scale rather than falling into a simple event category. For this study, the endpoint is each participant’s change in AIMS component movement score from baseline to the end of the study. The mean describes the average change across the analyzed participants. The standard deviation describes how spread out participant-level values are around that mean. It is not the same as a confidence interval: the standard deviation describes variability among observations, while a confidence interval describes uncertainty in an estimated quantity.
The registry identifies the Safety Set as the population for reporting the overall AIMS change. It does not provide the size or detailed definition of that analysis population. The record also does not report the actual mean, standard deviation, confidence interval, or test result for this endpoint. Without those estimates, the primary outcome cannot be interpreted for direction, magnitude, variability, or precision. The number enrolled is not a substitute for an endpoint result, and a study’s enrollment alone does not show whether an effect was detected.
What does the sequential design permit?
The study proceeds from roluperidone monotherapy to roluperidone with olanzapine. A sequential design can describe observations made during successive treatment periods, but it does not provide the same basis for comparison as randomized groups receiving different treatments over the same period. Here, the allocation is listed as non-randomized, masking is absent, and the model is sequential. Consequently, treatment phase and time in the study are linked. Any difference between observations in the phases could not automatically be attributed to the addition of olanzapine. The registry does not report an analysis designed to separate treatment effects from phase or time effects.
The study is not a randomized comparison, and the registry explicitly notes that the arms are not a like-for-like control comparison. The phase-specific safety counts should therefore be read as descriptive counts within the treatment sequence, not as an estimate of a randomized contrast. Differences in phase duration and the number at risk also affect the opportunity to observe events. No event-rate analysis or phase-adjusted safety comparison is reported in the registry record.
How should planning illustrations be understood?
Sample-size calculations based on an observed effect are planning illustrations, not evidence of what was observed in this study. The record describes such illustrations as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those assumptions describe hypothetical planning, not the study’s sequential, non-randomized treatment structure. The record does not report a sample-size justification for the trial’s own design. Any calculated number of participants per arm is a planning scenario; it is not the number enrolled in this study and is not observed power. Because the primary endpoint estimate itself is not reported, a reader cannot independently assess an observed effect from the registry entry.
In general, a significance level sets a decision threshold for a specified statistical test under its assumptions. It does not describe the probability that a treatment effect is real, and it does not measure the clinical importance of an estimate. A confidence interval is often useful alongside a point estimate because it communicates the range of values compatible with the data under the analysis. Neither a confidence interval nor a p-value for the primary AIMS endpoint is reported in the registry record. No inferential result should be inferred from the planning assumptions alone.
Why do distributional assumptions matter?
A normal approximation is a mathematical approach used in some planning calculations. Its usefulness depends on whether the approximation is suitable for the outcome and design being considered. For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes; a model that ignores this can misstate uncertainty. This is general statistical context, not a description of an analysis reported for this trial. The registry record does not report a distributional assessment, a model for the primary endpoint, or an over-dispersion analysis.
The AIMS change score is bounded by the scale’s scoring rules, and the record specifies a mean and standard deviation as its summary. Those summaries may describe the data, but their adequacy for inference depends on the observed distribution and analysis assumptions. The registry does not give participant-level values or distributional diagnostics. There is therefore no basis in the posted record to judge whether a particular inferential model was used or whether its assumptions were checked.
The pharmacokinetic outcomes are listed as measures of concentration over time and related summaries, including Cmax, Tmax, AUC 0-24, and AUC Inf. These are distinct outcome measures and may require summaries suited to their distributions and sampling structure. The registry lists the measures but does not report their numerical estimates or the statistical methods used to analyze them. It also does not report how incomplete pharmacokinetic sampling, if any, was handled.
In short, the methods information supports understanding of the endpoint definition, the sequential design, and the assumptions used for planning illustrations. It does not establish the analysis model for the primary endpoint, the inferential procedure, or the handling of missing observations. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and identifies the AIMS change-from-baseline measure as the primary outcome. It also lists pharmacokinetic outcomes for roluperidone and olanzapine: maximum plasma concentration, time to maximum plasma concentration, AUC 0-24, and AUC Inf for each drug. The record does not report a multiplicity strategy, such as whether or how statistical testing across multiple outcomes was adjusted. It also does not report a hierarchy for interpreting the secondary outcomes. Where several outcomes are assessed, repeated testing can increase the chance of at least one apparently unusual result by chance; this is general statistical context, not a claim about a result in this study.
Missing-data methods are not reported in the registry record. The study summary describes planned treatment periods and an inpatient stay, but does not state how missing AIMS assessments, withdrawals, or incomplete pharmacokinetic samples were handled in analysis. The registry also does not give the number of participants with observed endpoint data or the reasons for any absent measurements. Enrollment and the number at risk for safety reporting do not establish the number with complete primary endpoint data.
The primary endpoint is described as reported for the Safety Set, but the record does not define that set or state its size. It does not identify other analysis populations or explain whether their membership differed. These omissions make it difficult to connect the listed enrollment with the participants contributing to each outcome. The statistical analysis plan, analysis-population definitions, and missing-data procedures are not reported in the registry record, so conclusions about their effects cannot be drawn.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment Phase 1 | 1 | 17 | 5.9% |
| Treatment Phase 2 | 0 | 15 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Phase 1 | 0 of 17 |
| Treatment Phase 2 | 0 of 15 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Phase 1 | 5 of 17 |
| Treatment Phase 2 | 5 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Phase 1 | Treatment Phase 2 |
|---|---|---|---|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | 1 of 17 | 0 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Phase 1 | Treatment Phase 2 |
|---|---|---|---|
| Dizziness | Nervous system disorders | 0 of 17 | 3 of 15 |
| Headache | Nervous system disorders | 2 of 17 | 0 of 15 |
| Somnolence | Nervous system disorders | 0 of 17 | 2 of 15 |
| Presyncope | Nervous system disorders | 1 of 17 | 0 of 15 |
| Syncope | Nervous system disorders | 0 of 17 | 1 of 15 |
| Alanine aminotransferase increased | Investigations | 1 of 17 | 0 of 15 |
| Blood creatine phosphokinase increased | Investigations | 1 of 17 | 0 of 15 |
| Electrocardiogram T wave inversion | Investigations | 0 of 17 | 1 of 15 |
| Heart rate increased | Investigations | 1 of 17 | 0 of 15 |
| Agitation | Psychiatric disorders | 1 of 17 | 0 of 15 |
Serious events with the highest arm-level rate: rhabdomyolysis (5.9%).
The registry lists serious and other adverse event counts separately for each treatment phase, with the number at risk shown for each. Treatment Phase 1 lists 17 at risk, 1 serious adverse event, and 5 other adverse events. Treatment Phase 2 lists 15 at risk, 0 serious adverse events, and 5 other adverse events. The record lists 0 deaths in both phases. Rhabdomyolysis is included among the top serious adverse event terms with a listed value of 5.9%.
These are descriptive registry counts, not proof that treatment caused or prevented an event. The phases occurred in sequence rather than in randomized, concurrent groups, and the at-risk counts differ. The treatment periods also differ in duration: roluperidone monotherapy was planned for 7 days, while co-administration was planned for 10 days. Counts across these periods should not be treated as a direct comparison of risk without accounting for exposure and study structure. The registry does not report a comparative safety model or causal attribution for the listed events.
The listing of 5.9% with rhabdomyolysis should be read as the value attached to that term in the record, not as an independent estimate of causation. The registry does not report additional detail about event timing, severity beyond the serious-event classification, management, or relationship to either drug. A zero count in a phase means no event was listed for that category in that phase; it does not establish that the underlying risk is zero.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed Phase 1 study evaluated a sequence of roluperidone monotherapy followed by co-administration with olanzapine in adults with moderate to severe negative symptoms of schizophrenia. It specifies doses, treatment periods, the primary AIMS endpoint, and selected safety counts. It also identifies pharmacokinetic outcomes for both drugs. These details describe the scope and structure of the investigation.
The registry record does not report the numerical result for the primary AIMS endpoint or the listed pharmacokinetic outcomes. It therefore does not establish the average change in movement score, the spread of observed scores, or the precision of an estimate. It also does not provide an inferential result that would support a statistical comparison. The endpoint description alone is not an outcome finding. The absence of a posted estimate should not be interpreted as evidence of no change or no effect.
The phase-specific adverse-event counts can be described, but they cannot establish a causal effect of either treatment. Participants were not randomized to concurrent comparison groups, masking was absent, and the sequence linked treatment phase with time. The counts also come from phases with different numbers at risk and different planned durations. The registry does not report an analysis that adjusts for those features or a comparison against a control group.
More broadly, a result from a small Phase 1 study would need to be interpreted in light of its design, endpoint definitions, analysis population, and uncertainty. The registry entry does not report the primary estimate or its uncertainty, the missing-data approach, or the statistical analysis plan. It cannot answer questions about the size or precision of the primary outcome from the information listed. It also cannot establish how the observations would apply beyond the study population and treatment sequence described.
The appropriate statistical reading is therefore limited and specific: the registry documents the study’s design and selected event counts, but the numerical primary and pharmacokinetic findings are not reported in the registry record. No conclusion about whether the treatment sequence changed AIMS scores or produced a particular pharmacokinetic pattern can be drawn from the posted results described in this entry.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why design structure shapes interpretation. A sequential, non-randomized study can document observations during monotherapy and subsequent co-administration, but it does not create a randomized estimate of the effect of adding olanzapine. Treatment phase and time are intertwined, and the registry does not describe a concurrent control group. Recognizing that distinction prevents descriptive phase counts from being read as if they came from a controlled treatment contrast.
The record also illustrates the difference between an endpoint definition and an endpoint result. It defines the AIMS score, identifies the change-from-baseline outcome, and states that the result is expressed as a mean with standard deviation. Yet the numerical endpoint result is not reported in the registry record. Clear definitions are useful, but they cannot substitute for an estimate and a measure of its uncertainty. Without those values, readers cannot judge the magnitude or precision of the primary outcome.
Safety counts also require context. The numbers at risk differ between phases, exposure durations differ, and the treatment periods occur in sequence. Reporting counts by phase is descriptive, but it does not by itself quantify comparative risk. The record’s serious-event listing and death counts can be accurately described without assigning causation or treating zero events as proof of zero risk.
Finally, the registry distinguishes the trial’s observed enrollment from hypothetical planning illustrations based on an observed effect. Such illustrations concern future design choices under stated assumptions; they do not demonstrate that the current study had a particular level of power. The trial’s own sample-size justification is not reported in the registry record. Taken together, these points show why statistical interpretation depends not only on numerical summaries, but also on the design, analysis population, missing-data handling, and completeness of results reporting.
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 limitation for interpreting the posted findings is that the primary endpoint’s numerical result is not reported in the registry record. The same is true for the listed pharmacokinetic outcomes. Without estimates and uncertainty measures, the entry does not allow readers to assess the magnitude, direction, or precision of those outcomes. The registry does not report confidence intervals or p-values for the primary endpoint.
The design is non-randomized, unmasked, and sequential, with no like-for-like control comparison. The monotherapy phase precedes co-administration, so treatment phase is inseparable from study time in the described sequence. This limits causal interpretation of differences between phases. The record does not report an adjusted analysis intended to address that design feature.
Enrollment was 17 overall, while the safety summaries list 17 at risk in Treatment Phase 1 and 15 in Treatment Phase 2. The record does not explain the difference in phase denominators or report the number contributing to the primary endpoint. It also does not define the Safety Set, detail participant-level completion, or report reasons for missing observations. Missing-data handling is not reported in the registry record.
The registry does not report a sample-size justification for the study’s own design, the statistical analysis plan, a multiplicity approach, or planned interim analyses. It gives a description of planning assumptions for illustrations, but those do not establish the rationale or inferential performance of this trial. Event timing, seriousness details beyond the listed classification, and causal attribution are also not described in the available record. These gaps limit the conclusions that can be drawn from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Co-Administration of Roluperidone and Olanzapine in Adult Subjects With Moderate to Severe Negative Symptoms of Schizophrenia — NCT06107803.
- Registry record last updated 2025-03-26; status last verified 2025-03.
- Results first posted 2025-03-26.
- 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.
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18. Record Summary
NCT06107803 is a completed Phase 1 study sponsored by Minerva Neurosciences. The registry describes a non-randomized, unmasked, sequential inpatient study in adults with moderate to severe negative symptoms of schizophrenia. Enrollment was 17. The listed study start date is 2023-10-13, and the primary completion date is 2024-01-12.
Participants were to receive roluperidone 64 mg daily for 7 days, followed by roluperidone 64 mg and olanzapine 10 mg together daily for 10 days. The primary outcome was change from baseline to Day 17 in AIMS component movement score, summarized as a mean and standard deviation. The numerical primary result and listed pharmacokinetic results are not reported in the registry record.
Safety listings include 1 serious adverse event in Treatment Phase 1 and 0 in Treatment Phase 2, with 5 other adverse events in each phase and 0 deaths in both. These are descriptive counts from a sequential study, not a randomized comparison or proof of causation.