AGN-Cogni.Q Acute Dose Safety and Pharmacokinetics Dose-Response in Prostate Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AGN-Cogni.Q Acute Dose Safety and Pharmacokinetics Dose-Response in Prostate Cancer Patients (NCT05375539), a na phase 1 study. The primary outcome is Cardiac Safety Via Electrocardiography (EKG).

2. Clinical Question

The study asks whether acute administration of AGN-Cogni.Q across dose levels is associated with treatment-emergent cardiac rhythm or repolarization abnormalities in prostate cancer patients, and what pharmacokinetic and other short-term safety measurements accompany dosing. The design addresses changes around individual dose occasions rather than comparing a treatment group with a separate control group.

The registry also lists pharmacokinetic measurements, immune-cell percentage changes, body temperature, and treatment-emergent adverse events as secondary outcomes. These outcomes broaden the acute-dose assessment, but the registry record does not report numerical results for the primary EKG endpoint or the listed secondary outcomes.

3. Trial Design

This was a phase 1, completed study sponsored by Milton S. Hershey Medical Center. The registry reports a start date of 2023-05-02, a primary completion date of 2025-02-15, and enrollment of 12. Allocation is recorded as not applicable, masking as none, and the model as sequential. These features describe a non-randomized, unmasked, within-subject dose-escalation study, not a conventional parallel-group trial.

The intervention is AGN-Cogni.Q. Its arm descriptions specify 800 mg, 1,200 mg, and 1,600 mg dose levels, with the stated fasting instructions. In this design, participants could contribute data to more than one dose-level group. Dose-level observations therefore cannot automatically be treated as observations from independent groups: the same person may appear in multiple groups, and characteristics of that person are shared across those observations.

The registry gives a primary endpoint focused on treatment-emergent EKG abnormalities, alongside secondary outcomes covering peak plasma concentrations of D, DA, and DOH; a plasma concentration-versus-time curve; changes in NK, CD4+ T, and CD8+ T cell percentages at 24 hours; body temperature through 24 hours after dosing; and the number of participants with treatment-emergent adverse events. The registry record does not report the detailed dosing sequence, criteria for moving between dose levels, or the protocol’s sample-size justification.

The adverse-event breakdown includes a 2000 mg group, while the intervention arm descriptions specify dose levels through 1,600 mg. The registry record does not explain this difference. That limits interpretation of how the listed adverse-event groups map to the described dose-escalation schedule. No separate control group or randomized dose assignment is reported, so comparisons across dose levels should be understood as descriptive rather than as randomized treatment contrasts.

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: This was a sequential within-subject dose-escalation study. Twelve participants received the 800 mg dose. Two participants discontinued after this period due to adverse events and did not proceed to higher doses. Ten participants continued to the 1200 mg and 1600 mg doses. Five participants enrolled during the escalation stage proceeded to the 2000 mg dose.

Dose 800 mg

Dose 1200 mg

Dose 1600 mg

Dose 2000 mg

Analysis population for the primary outcome, as defined in the registry: This was a sequential within-subject dose-escalation study. Arms are defined by dose level. Participants could contribute data to multiple arms due to the within-subject dose-escalation design.

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: The baseline analysis population includes all subjects who were enrolled and received at least one dose of the study intervention (800 mg). This population (N=12) was used for all demographic and baseline safety characteristic assessments.

6. Primary Endpoint

The registry lists the primary outcome as Cardiac Safety Via Electrocardiography (EKG), measured over Baseline (pre-dose) and 5 hours post-dose on each dosing day and at 24 hours (Up to 5 weeks)..

The primary endpoint counts participants with treatment-emergent EKG abnormalities. The registry describes 12-lead EKG assessment of cardiac rhythm and repolarization, with measurements at baseline before dosing, 5 hours after dosing on each dosing day, and 24 hours. The stated endpoint timeframe is up to 5 weeks. It is a participant count: the outcome concerns how many participants had an abnormality, not the total number of abnormal EKG readings or the severity of an abnormality.

EKG monitoring is used in a safety assessment because it can detect changes in cardiac electrical activity. Repeated measurements around dosing can help describe whether abnormalities were recorded after administration and how observations relate to the pre-dose baseline. That general rationale does not itself establish that a change was caused by the intervention; interpretation depends on the observed results and the study design.

The registry record does not report the number of participants with treatment-emergent EKG abnormalities, the types of abnormalities, or an estimate comparing measurements over time or across doses. It therefore does not provide a numerical primary-endpoint result from which the frequency or precision of this outcome can be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: a participant either had a treatment-emergent EKG abnormality recorded or did not, according to the endpoint definition. A count is an intuitive summary for this kind of outcome. To judge the precision of a count, readers ordinarily also need the number assessed and, where available, an uncertainty interval. The registry record does not report a primary-endpoint count or interval.

Why the dose-escalation structure matters

In a sequential within-subject study, dose levels are encountered in sequence, and one participant may contribute observations at more than one level. This can allow observations to be considered within the same person, but it creates dependence between dose-level records. Analyses that treat every dose group as unrelated may fail to reflect that shared participant history. The registry describes this within-subject contribution but does not report a statistical method that accounts for it in an analysis.

Random allocation and masking are not reported as features of this study: allocation is listed as not applicable and masking as none. Therefore, the design does not provide the protection against selection or assessment biases that randomization or masking can offer. This is a design consideration, not evidence that bias occurred. The registry record does not describe safeguards or procedures that might otherwise address these concerns.

Counts, estimates, and uncertainty

A participant count is a descriptive result. A statistical comparison would require a defined contrast, an analysis method suited to the design, and information about the observed data. A confidence interval, when reported, expresses a range of values compatible with the data and the analysis assumptions; it does not guarantee that the true value lies in that range. The primary EKG endpoint has no posted count or confidence interval, and the registry record does not report a statistical test for it.

For outcomes measured over time, such as plasma concentration versus time or body temperature through 24 hours, analyses may need to account for the timing and repeated measurements. For participant-level binary outcomes, the analysis may focus on how many people experienced an event. These are general statistical considerations; the registry record does not report the specific methods used for the listed secondary outcomes, or their numerical results.

Over-dispersion and repeated data

Over-dispersion is a general issue in count analyses: observed variation can exceed what a chosen statistical model expects. It matters because a model that understates variation can produce uncertainty estimates that are too narrow. The registry record does not report an over-dispersion assessment or a count model for this study. More fundamentally, some listed results are participant counts, and dose-level observations may be repeated within people; dependence among observations is a separate issue that an analysis may need to address.

Planning calculations

Any sample-size figures associated with this analysis are planning illustrations rather than observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Such illustrations help show how assumed effect size and design choices relate to a target sample size; they do not describe the trial’s enrollment plan or establish that the study had a particular probability of finding a result. The registry record does not report a sample-size justification for the trial. No planning sample-size values are repeated in this explanation.

The listed planning framework refers to two-arm comparisons, whereas this study is described as sequential and within-subject, with no randomized control group. A planning illustration based on equal allocation between two arms should not be mistaken for a design-specific calculation for this study. The registry record does not report a sample-size method tailored to the repeated, sequential dose structure.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary EKG safety outcome and secondary measures covering pharmacokinetics, immune-cell percentages, body temperature, and treatment-emergent adverse events. Considering several outcomes can raise a multiplicity issue: the more statistical tests conducted, the greater the general chance of at least one apparently notable result arising by chance. Whether and how to adjust for multiple testing depends on the analysis plan and the role assigned to each outcome. A multiplicity adjustment or hierarchy among outcomes is not reported in the registry record.

The registry lists seven outcome measures and four analyses, but those counts alone do not show which outcomes were analyzed together, how tests were selected, or whether any adjustment was used. Numerical results and inferential details for the primary EKG outcome and listed secondary outcomes are not reported in the registry record. This prevents assessment of the size and precision of results and of how any multiple testing was handled.

Missing-data methods and the amount of missing outcome data are not reported in the registry record. The analysis population for the EKG outcome, including which participants or dosing occasions contributed to any analysis, is also not reported beyond the description that participants could contribute to multiple dose groups. The record does not describe exclusions, incomplete follow-up, or how missing measurements would be treated.

Those omissions matter because repeated EKG and pharmacokinetic measurements can be unavailable at some time points, and a participant-level count depends on the data used to classify each participant. Without information about missingness and analysis populations, readers cannot determine whether the posted counts represent all enrolled participants, all participants assessed at a dose level, or a narrower analysis set.

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 serious adverse-event counts are zero in all four listed groups: 800 mg has 0 among 12 at risk, 1,200 mg has 0 among 10, 1,600 mg has 0 among 10, and 2000 mg has 0 among 5. The death count is also zero in each group. These figures mean that no participants with a serious adverse event or death are recorded in those group summaries; they do not establish that the underlying risk is zero.

The other-adverse-event counts are 3 among 12 at 800 mg, 4 among 10 at 1,200 mg, 2 among 10 at 1,600 mg, and 2 among 5 at 2000 mg. These summaries count participants with an event, not all event occurrences. The registry does not provide event descriptions in these group figures, so they do not show which events occurred or whether they were judged related to AGN-Cogni.Q.

Because participants could contribute to multiple dose groups, the groups should not be read as independent sets of people. The 2000 mg group is included in the adverse-event breakdown, although the listed intervention descriptions specify doses through 1,600 mg; the registry record does not explain this difference.

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

The registry record establishes that the study was designed to examine acute safety and pharmacokinetics of AGN-Cogni.Q in prostate cancer patients, with cardiac safety assessed by EKG. It also reports adverse-event counts by dose group. Those data describe the recorded experience in the listed groups, including zero serious adverse events and zero deaths in each group, along with nonzero counts for other adverse events.

The information does not establish the frequency of treatment-emergent EKG abnormalities, because the numerical primary endpoint result is not reported in the registry record. Nor does it provide results for the listed pharmacokinetic outcomes, immune-cell changes, or body-temperature measures. Without those results, readers cannot evaluate the magnitude, variation, or precision of those endpoints.

The design is not a randomized comparison against a separate control group. Participants could contribute to multiple dose levels, so differences between the listed groups cannot be read as independent, like-for-like comparisons. The adverse-event counts alone do not establish a causal relationship, a dose-response pattern, or how the results compare with outcomes under another condition.

Zero serious events in the posted group summaries are reassuring only in the narrow descriptive sense that none are recorded among the participants listed in those groups. They do not rule out uncommon events or quantify risk with precision. The registry does not report uncertainty intervals for these counts. Overall, the record describes the study’s safety questions and some event counts, while leaving the central EKG result and several planned outcome results unreported.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines a sequential dose-escalation structure with repeated contribution by participants across dose levels. The distinction matters: dose groups may share participants, so a comparison that treats each group as independent can misrepresent the structure of the data. Understanding who contributed at each level and how analyses accounted for repeated observations is important for interpreting any dose-level pattern.

The primary endpoint is a participant-level safety count based on EKG abnormalities, assessed at multiple time points. This makes clear that the analysis question is not simply whether an abnormal reading occurred at one instant; it concerns participants meeting the treatment-emergent endpoint over the stated measurement schedule. However, the numerical endpoint result and its uncertainty are not reported in the registry record, limiting statistical interpretation.

The adverse-event summaries also illustrate the difference between a count and an estimate of risk. Counts are useful descriptions of observed participants, but their interpretation depends on group size, overlap between groups, event definitions, and follow-up. Here, the group sizes differ, participants may contribute to multiple levels, and the registry record does not explain the 2000 mg group’s relationship to the dose levels described for the intervention.

Finally, the registry record lists several secondary outcome domains alongside the primary safety outcome. A clear statistical interpretation would depend on the analysis methods, missing-data handling, and approach to multiple outcomes. Those details are not reported. The study therefore highlights why design structure and completeness of outcome reporting are as important as the endpoint labels themselves.

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 record does not report numerical results for the primary EKG endpoint, so the main cardiac-safety outcome cannot be quantified from the posted endpoint information. Results for the listed pharmacokinetic, immune-cell, and temperature outcomes are also not reported in the registry record. The available adverse-event summaries do not include descriptions of the events or a reported assessment of their relationship to the intervention.

Enrollment is reported as 12, and the adverse-event group counts are small. Zero serious events in these groups do not exclude uncommon events, and the record does not provide uncertainty intervals to indicate the precision of those counts. Participants could contribute to multiple dose groups, so the reported group counts do not represent independent treatment arms.

The design is sequential, unmasked, and non-randomized, with allocation listed as not applicable. There is no separate randomized control group for a like-for-like comparison. The registry record does not report the detailed sequence, progression criteria, or statistical methods used to account for repeated observations. It also does not report missing-data methods, analysis-population definitions, or a multiplicity approach.

The adverse-event summary includes a 2000 mg group, although the intervention descriptions list dose levels through 1,600 mg. The registry record does not explain the difference, which makes the relationship between the reported group and the described dosing plan unclear. The trial’s sample-size justification is not reported in the registry record, and planning illustrations based on two-arm assumptions should not be read as a description of this within-subject design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: AGN-Cogni.Q Acute Dose Safety and Pharmacokinetics Dose-Response in Prostate Cancer Patients — NCT05375539.
• Registry record last updated 2026-06-02; status last verified 2026-05.
• Results first posted 2026-05-06.
• 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

NCT05375539 is a completed phase 1 study of AGN-Cogni.Q in prostate cancer patients, sponsored by Milton S. Hershey Medical Center. The registry reports a start date of 2023-05-02, primary completion on 2025-02-15, and enrollment of 12. The design is sequential, unmasked, and within-subject, with participants able to contribute to multiple dose groups.

The primary outcome is the number of participants with treatment-emergent EKG abnormalities, assessed at baseline, 5 hours after dosing on each dosing day, and 24 hours, over up to 5 weeks. Numerical primary-endpoint results are not reported in the registry record. The adverse-event summaries report no serious events or deaths in the listed groups and provide counts of participants with other adverse events. The registry record does not explain the 2000 mg adverse-event group, although the intervention descriptions list dose levels through 1,600 mg.