Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies (NCT03888222), a randomized phase 2 study. The primary outcome is Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events..

2. Clinical Question

The study is titled as an evaluation of bosutinib’s impact on safety, tolerability, biomarkers, and clinical outcomes in DLB. Its registry-listed primary outcome, however, focuses on safety and tolerability: it describes a Go/NoGo determination based on emergent adverse events, with a 25% discontinuation criterion. The record names myelosuppression, urinary, pancreatic, and hepatic disorders, and QTc prolongation as adverse events of interest. It does not report the final Go/NoGo determination or a numerical result for the primary outcome.

The registry also lists secondary measures of cerebrospinal fluid (CSF) and plasma biomarkers, tyrosine-kinase absorbance, and bosutinib concentrations and exposure. Those measures could describe biological or pharmacokinetic responses, but the record contains no analysis results for them. The central question that can be assessed from the posted information is therefore limited: what safety-event counts are recorded for the two arms, and what conclusions cannot be drawn without the missing outcome analyses?

3. Trial Design

This was a phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Georgetown University. Randomization is intended to allocate participants by chance rather than by clinical judgment. In a parallel-group design, each participant is assigned to one arm rather than receiving both study treatments in sequence. The record identifies quadruple masking but does not specify which groups of people were masked.

The planned arms are described as a matching placebo and 100 mg of bosutinib, each taken orally once daily for 3 months (90 days). The arm descriptions state that 30 participants would be recruited and randomized in a 1:1 allocation, with 15 in each arm. Separately, the registry records enrollment of 26 participants. It does not explain the difference between the planned arm numbers and the enrollment figure, or give arm-specific enrollment totals. The adverse-event summary lists 13 participants at risk in each arm.

The study start date is 2019-04-23, the primary completion date is 2021-08-27, and the status is completed. The primary outcome timeframe is 12 weeks. The record does not establish whether outcome collection continued beyond that timeframe or describe any longer-term follow-up.

Randomization and masking can help limit certain sources of bias, but they do not by themselves establish that outcomes were measured or analyzed in a particular way. The registry record does not report the randomization sequence method, allocation concealment procedures, details of who was masked, or procedures for evaluating masking. It also does not state the protocol’s sample-size justification or provide a participant-flow account. These omissions limit assessment of how closely the completed study followed its intended design.

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

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 Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events., measured over 12 weeks.

The primary outcome is titled as a safety and tolerability Go/NoGo determination, with a 25% discontinuation criterion, based on emergent adverse events. Its stated timeframe is 12 weeks. The description identifies events of interest as myelosuppression, urinary, pancreatic, and hepatic disorders, and QTc prolongation, referring to the bosutinib investigator brochure. The outcome is recorded as a number of events.

A safety endpoint is used to characterize unwanted events and treatment discontinuation during study participation. A Go/NoGo rule can give a study team a prespecified decision framework for whether safety findings support proceeding to further evaluation. In general, the decision depends on how the rule is defined and how the observed safety data are collected and classified. The registry record does not report the full decision procedure, whether discontinuations were all attributed to adverse events, or how the 25% criterion was applied.

The posted record does not give a primary-endpoint event count, discontinuation count, or final Go/NoGo decision. The adverse-event summary lists serious and other adverse events by arm, but it does not identify those counts as the primary outcome result or map them to the specified events of interest. Those figures therefore cannot substitute for a reported primary-endpoint analysis.

The distinction matters: a description of what the investigators intended to assess is not itself an observed result. Without the endpoint result and its analysis, the primary safety question remains unanswered by the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization and masking. In general, randomization assigns participants to treatment groups using a chance-based method. This helps guard against systematic differences in who enters each arm, although it cannot guarantee that groups will be similar on every characteristic, especially in a small study. The registry identifies the study as randomized and quadruple-masked. Masking generally aims to reduce the influence of treatment knowledge on participant experience, care, or outcome assessment. The record does not specify the randomization procedure, allocation concealment, or which people were included in the masking description, so those protections cannot be assessed in detail.

Parallel-group comparison. A parallel design assigns each participant to one study arm. The stated comparison is bosutinib against matching placebo, with planned 1:1 allocation. The record does not give an analyzed comparison of the arms. Nor does it report baseline characteristics that would help readers assess the groups’ comparability after randomization. In general, group-level outcome comparisons need to be interpreted in light of both the assignment process and the participants included in the analysis.

Safety counts. The adverse-event summary reports participants at risk, participants affected by serious and other adverse events, and deaths for each arm. Such counts are descriptive. They do not, by themselves, account for differences in exposure time, event recurrence, event severity, or the timing of events. The record does not state whether the affected-participant counts include people with multiple events or how events were coded. In general, safety interpretation is clearer when event definitions, grading, attribution, exposure, and participant-level follow-up are available alongside the counts.

Primary endpoint. The stated primary outcome is a number of events over 12 weeks, within a safety and tolerability Go/NoGo framework. The record names categories of adverse events of interest and a discontinuation criterion, but does not post the primary outcome analysis. It does not describe a statistical model, a comparison measure, a confidence interval, or how the decision rule was applied. A numerical endpoint definition is not enough to reconstruct the result when the observed primary outcome data and analysis are absent.

Secondary outcomes. The registry lists biomarker and pharmacokinetic measures in CSF and plasma. The outcomes include absorbance levels related to tyrosine kinases, maximum bosutinib concentration (Cmax), the time of peak concentration (Tmax), area under the curve (AUC), and changes in biomarkers and biomarker ratios. In general, Cmax characterizes a peak concentration, Tmax describes when that peak occurs, and AUC represents exposure over time. These measures answer different questions and may use different units. The record provides no results, units for every listed measure, analysis methods, or timing details for the measurements. No outcome analysis can be reconstructed from the titles alone.

Uncertainty and inference. A confidence interval, in general, gives a range of values compatible with the data under a specified statistical method and assumptions. It helps communicate the precision of an estimate; a point estimate without an interval can hide substantial uncertainty. No confidence intervals or treatment-effect estimates are listed for the primary or secondary outcomes. No p-values or other inferential results are listed either. The absence of these statistics means readers cannot assess the precision or statistical compatibility of any between-arm difference from the registry record.

Planning illustrations. The record describes a planning-illustration approach based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is set as a stated fraction of the observed effect; for time-to-event calculations, the illustration concerns total events, while other calculations concern participants per arm. These are planning assumptions, not reported evidence of observed power, and they are not a substitute for a protocol-based sample-size justification. The registry record does not report the trial’s own sample-size justification or give enough outcome analysis detail to interpret a planning calculation as a trial result.

Over-dispersion and count outcomes. In general, count data can vary more than a simple statistical model assumes; this is called over-dispersion. If present and not accounted for, it can make uncertainty estimates too narrow. Whether over-dispersion is relevant depends on the outcome and model. The record does not report a model for the primary event count, a dispersion assessment, or any other count-data method. No conclusion about the adequacy of such modeling can be drawn.

Analysis population and missing observations. Statistical interpretation also depends on who was included in each analysis and how incomplete measurements were handled. An intention-to-treat analysis, in general, retains participants in their randomized groups, while other analysis populations may apply additional criteria. The registry record does not identify the population used for any outcome analysis, describe exclusions, or give a missing-data method. As no outcome analyses are posted, it is not possible to determine whether missing observations affected the results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including pharmacokinetic measures and changes in CSF and plasma biomarkers. When a study examines several outcomes, the chance of finding at least one apparently notable result can be affected by how many statistical tests are performed and how they are interpreted. In general, a prespecified multiplicity strategy can help define how evidence across outcomes will be evaluated. The registry record does not report whether a multiplicity adjustment or hierarchical testing plan was used. It also does not report statistical results for the listed secondary outcomes, so no claims about those measures can be evaluated from the record.

Missing-data methods and analysis populations are not reported in the registry record. It does not describe the number of participants with measurements available for each outcome, withdrawals, reasons for discontinuation, or how missing values were handled. These details matter because incomplete observations can affect an estimate, particularly if missingness is related to treatment experience or outcome status. No assumption about the reasons for missing data can be made from the posted information.

The record also does not state whether interim analyses were planned or conducted, or provide a statistical analysis plan. The primary outcome is described, but its analysis method and final Go/NoGo determination are absent. Without the planned analysis details and reported results, readers cannot assess whether outcomes, populations, or methods were selected after observing the data.

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 non-serious adverse event terms

The adverse-event summary lists 13 participants at risk in each arm. In the placebo arm, 0 participants are listed as affected by serious adverse events, 6 by other adverse events, and 0 deaths. In the 100 mg bosutinib arm, the corresponding counts are 0, 6, and 0. The figures are counts of affected participants as recorded in the safety summary; they are not a full description of every event.

The registry does not provide the names of the other adverse events, their severity, timing, duration, or suspected relationship to treatment. No serious-event terms are listed. The counts also do not show whether a participant experienced more than one event. They should not be read as proof that no serious event could occur or that the two arms have equivalent safety. The record does not connect these broad categories to the primary Go/NoGo decision or report discontinuation counts. Therefore, the safety summary offers limited descriptive information but does not resolve the primary endpoint.

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

The posted results establish what the adverse-event summary records for this study: the listed serious-event counts are 0 in both arms, the other-adverse-event counts are 6 in both arms, and deaths are listed as 0 in both arms. The registry records 26 participants enrolled and 13 participants at risk in each arm for the safety summary. These details describe the available safety counts; they do not provide a comparative estimate with uncertainty.

The record does not report the primary endpoint result or the Go/NoGo determination, even though the outcome is defined in terms of emergent adverse events and a 25% discontinuation criterion. It does not provide discontinuation counts or enough detail to establish whether any of the named events of interest occurred. Consequently, the observed broad safety counts cannot answer whether the stated criterion was met.

No analysis results are posted for the listed biomarkers, pharmacokinetic measures, or clinical outcomes. The registry does not provide estimates of treatment effects, confidence intervals, or significance tests. It is therefore not possible to determine from this record whether the arms differed on those outcomes or how precise any difference might be.

In general, a completed study can still have an incomplete public results record. Here, the status is completed, but several details needed for interpretation are absent. This record should not be treated as evidence that bosutinib did or did not improve clinical outcomes, nor as evidence that the arms have identical safety. It documents limited safety counts and the intended outcomes, while leaving the primary analysis and secondary results unreported.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry entry combines a defined safety decision framework with a small enrolled group and a sparse set of posted outcome results. The primary endpoint concerns adverse events and discontinuations, yet the registry does not give the primary outcome result or final Go/NoGo decision. That gap illustrates why outcome definitions and outcome findings must be distinguished: knowing what was intended to be measured does not show what was observed.

The record also illustrates the limits of reading broad adverse-event counts as a treatment comparison. The same affected-participant counts appear for serious and other events in the two arms, but no event-level detail, uncertainty estimates, or formal between-arm analysis is posted. General statistical reasoning cautions against treating matching counts in a modest-sized study as proof of equivalence. The degree of precision cannot be judged without an estimate and its uncertainty.

Several biological and pharmacokinetic outcomes are listed, which would address different questions from the primary safety endpoint. Their interpretation would require outcome-specific methods, measurement timing, analysis populations, and results. The absence of those details prevents a statistical assessment of the secondary aims and makes it important not to substitute the study title or endpoint list for evidence of an outcome effect.

Finally, the registry’s planned arm descriptions specify 30 participants, while its enrollment entry records 26. The record does not explain that difference. This is a reminder that planning descriptions, enrollment totals, and analyzed populations are distinct quantities. Transparent participant flow and complete analysis reporting are needed to connect them and support reproducible interpretation.

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 this specific trial is that the registry record does not report the primary outcome result or the stated Go/NoGo decision. It also does not provide discontinuation counts, despite naming a discontinuation criterion. The adverse-event summary is limited to broad categories and does not identify event terms, severity, timing, recurrence, or treatment attribution. The serious-event terms list is empty, so the record does not offer detail beyond the summary counts.

The record lists enrollment of 26, while the arm descriptions say 30 participants would be recruited, with 15 in each arm. It does not explain the difference, give a participant-flow account, or identify the number included in each outcome analysis. The safety summary gives 13 at risk in each arm, but that does not establish the analysis population for the primary or secondary outcomes.

There are no posted estimates, confidence intervals, significance tests, or results for the biomarker and pharmacokinetic outcomes. The statistical analysis plan, missing-data methods, multiplicity approach, interim-analysis information, and sample-size justification are not reported in the registry record. The record also does not describe eligibility criteria in detail, baseline characteristics, or who was masked. These omissions prevent assessment of analytic choices, precision, potential attrition effects, and the applicability of the findings. The completed status does not remedy the missing outcome analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies — NCT03888222.
• Registry record last updated 2026-07-10; status last verified 2026-06.
• Results first posted 2026-07-10.
• 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

NCT03888222 is a completed phase 2 randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Georgetown University. It enrolled 26 participants with dementia with Lewy bodies. The planned arms were matching placebo and 100 mg bosutinib, taken orally once daily for 3 months (90 days); the primary outcome timeframe is 12 weeks. The study started on 2019-04-23 and reached primary completion on 2021-08-27.

The primary outcome is a safety and tolerability Go/NoGo determination based on emergent adverse events, with a 25% discontinuation criterion. The adverse-event summary lists 13 participants at risk per arm, no serious adverse events or deaths in either arm, and 6 participants affected by other adverse events in each arm. The primary determination and analyses of the listed secondary outcomes are not reported in the registry record.