Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51 (NCT06390098), a na phase 1 study. The primary outcome is Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan.

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label, sequential PET study in healthy adult participants. The registry record lists an enrollment of 3 and describes the study as completed. It reports a start date of 2021-08-09 and a primary completion date of 2021-10-12. The sponsor was Asceneuron S.A.

Participants received ASN51 orally at low, medium, and high doses, as described in the arm information. Dosing took place on Day 1 of imaging sessions 2 and 3 before the PET scan during the study. Since the design was sequential and not randomized, the dose categories do not constitute randomized, like-for-like treatment groups. The record does not provide a parallel control arm or identify a placebo comparison.

For the primary PET outcome, participants received an intravenous dose of radiolabelled [18F]-IMA601 at the start of each PET scan. The scan schedule included a baseline scan and post-dose scans. The stated timing for PET Scan 2 was 6 hours post-dose for participant 1 and 31 hours post-dose for participants 2 and 3 on Day 1. PET Scan 3 was listed as 48 hours post-dose on Day 1 after the final ASN51 dose. These are the timing descriptions in the registry record; further detail on the scheduling rationale is not reported in the registry record.

The record lists 16 outcome measures and 0 analyses. It includes safety observations and measures related to ASN51 plasma concentration and estimated O-GlcNAcase receptor occupancy among the secondary outcomes. It does not report the protocol’s allocation rationale, a statistical analysis plan, or an explanation of how the reported outcome measurements were analyzed.

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

Analysis population for the primary outcome, as defined in the registry: PET population included all participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a pharmacokinetic (PK) result immediately preceding PET scan. Here, "number analyzed" signifies specific participant evaluated in respective arm at a specified timepoint.

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: All treated set included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan, measured over PET Scan 1 (Baseline), PET Scan 2 (6 hours post-dose [for participant 1] and 31 hours post-dose for [participants 2 and 3] on Day 1), PET Scan 3 (48 hours post-dose on Day 1) after final ASN51 dose.

The primary endpoint was regional total volume of distribution, or VT, of [18F]-IMA601 in the frontal lobe at each brain scan. VT is expressed in milliliters per cubic centimeter (mL/cm^3). Participants received the radiolabelled tracer intravenously at the start of each PET scan, and the record says participant-wise data were reported for this outcome.

In general, a PET tracer is used to obtain a signal related to a biological target or process. A volume-of-distribution measure describes the distribution of tracer in tissue relative to its concentration in plasma under the measurement model used. For this study, repeated measurements across baseline and post-dose scans were intended to characterize changes in the frontal-lobe PET measure in the context of ASN51 exposure. The registry record does not state the detailed measurement model or analysis used to translate VT into receptor occupancy.

The study’s broader question concerned the relationship between plasma concentration of ASN51 and brain target occupancy. Estimated O-GlcNAcase receptor occupancy by plasma concentration and PET scan was listed as a secondary outcome. The primary endpoint should therefore be read as a PET measurement relevant to the investigation, not as a reported direct numerical estimate of occupancy. Numerical VT values, occupancy estimates, and the relationship between them are not reported in the registry record. Without those results, the direction, size, and precision of any observed change cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and outcome descriptions determine what kinds of statistical interpretation are appropriate. This study was open-label and sequential, and allocation was not applicable. It was not a randomized comparison. The dose categories therefore should not be interpreted as independent treatment arms in a conventional parallel-group trial. In a randomized comparison, assignment is intended to support a fair comparison between groups. That protection is not described for these dose categories.

What does a sequential design imply?

In a sequential design, observations are collected in an ordered study structure rather than through a simple concurrent, randomized group comparison. Here, participants had PET scans at baseline and after dosing, and the dose descriptions refer to imaging sessions 2 and 3. Such repeated measurements can be useful for studying change within a participant and relating measurements to exposure. However, scan timing, dose order, and participant-level differences can matter when interpreting the pattern. The registry record does not report the statistical method used to handle these features.

The timing description specifies that PET Scan 2 occurred 6 hours post-dose for participant 1 and 31 hours post-dose for participants 2 and 3 on Day 1. PET Scan 3 was listed at 48 hours post-dose on Day 1 after the final ASN51 dose. Different timing can affect how measurements relate to plasma concentration and drug exposure. In general, an analysis of repeated PET measurements may need to account for within-participant dependence and the timing of each measurement. Whether such an analysis was performed is not reported in the registry record.

What does the primary measurement represent?

The primary outcome is regional VT of [18F]-IMA601 in the frontal lobe, measured using PET. VT is a quantitative tracer-distribution measure, not itself a reported receptor-occupancy percentage. The registry record states that the tracer was administered intravenously at the start of each scan and that participant-wise data were reported. A detailed calculation method, model specification, or transformation of VT into occupancy is not reported in the registry record.

The study’s scientific question links ASN51 plasma concentration with estimated O-GlcNAcase receptor occupancy. In general, a concentration–occupancy analysis estimates how a measured exposure relates to a target-related PET measure. Such analyses may use a fitted curve or another statistical model, but the particular form, assumptions, and fitting procedure for this study are not reported in the registry record. No concentration–occupancy estimate or uncertainty measure is reported, so readers cannot evaluate the strength or precision of the relationship from the registry information.

How should uncertainty be understood?

In general, a point estimate describes a measured or modeled quantity, while a confidence interval describes uncertainty around an estimate under the assumptions of the analysis. Confidence intervals can help distinguish a relatively precise estimate from one that is compatible with a broad range of values. The registry record does not report a numerical primary-endpoint estimate or confidence interval. No precision claim can therefore be made about the frontal-lobe VT measurements or the concentration–occupancy relationship.

The registry record lists 0 analyses. It does not report a test statistic or p-value for the primary outcome. A p-value, in general, summarizes how compatible data are with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Without a stated analysis and its results, statistical significance cannot be assessed. The record also does not describe a prespecified hypothesis test for the primary endpoint.

Why are group comparisons especially limited?

The dose groups are presented as low, medium, and high dose, but the trial was not randomized and was sequential. The safety information shows different numbers at risk in these dose categories, and the arm descriptions indicate dose administration across imaging sessions. These features mean a simple contrast between dose categories would not automatically represent a treatment effect. In general, comparisons can be confounded when groups differ in timing, exposure history, or other characteristics. A protocol and analysis plan would be needed to establish whether and how those issues were addressed; that information is not reported in the registry record.

For general context, over-dispersion occurs when observed variation is greater than expected under a statistical model. It can make standard errors too small if the model assumes less variability than is present. A small study with repeated measurements may be particularly sensitive to model assumptions and individual observations, but the registry record does not report a variance model or a specific over-dispersion assessment. No claim should be made that such a method was used or needed for the posted analysis.

The registry record lists 16 outcome measures, including safety, laboratory, vital-sign, ECG, physical-examination, plasma-concentration, and receptor-occupancy outcomes. It lists 0 analyses and does not describe a statistical plan, handling of repeated measurements, model diagnostics, missing-data procedures, or multiplicity adjustment. As a result, the statistical methods underlying any reported numerical results cannot be reconstructed from this information. The record’s design and endpoint descriptions support an account of what was intended to be measured, but not a quantitative assessment of the primary result.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures, covering the primary PET endpoint and secondary safety and pharmacokinetic or receptor-occupancy outcomes. It lists 0 analyses. No statistical analysis plan, hierarchy of hypotheses, or procedure for controlling multiplicity is reported in the registry record.

In general, multiplicity arises when several outcomes, time points, groups, or statistical tests are considered. The more analyses that are performed, the greater the chance that a result appears noteworthy by chance if each test is treated separately. A prespecified hierarchy or adjustment can help clarify which results are confirmatory and how uncertainty should be interpreted. Since the registry record does not describe such a plan or report inferential tests, it is not possible to determine whether multiplicity was addressed.

The primary outcome was measured at multiple scans, including baseline and post-dose scans. The record does not explain how the repeated measurements were combined or compared, or whether a specific scan or contrast was designated for inference. It also does not provide a numerical result for the endpoint.

The analysis population is described as participants who received study medication, had a baseline PET scan, at least one post-baseline PET scan, and a pharmacokinetic result immediately preceding a PET scan. The record does not report how many participants met that definition for each measurement, or whether anyone was excluded from an analysis. Missing observations, reasons for missingness, and methods for handling missing data are not reported in the registry record. These omissions limit assessment of whether the measurements available for analysis could differ systematically from those not available.

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 registry record reports participant counts for serious and other TEAEs. In the all-participants group, 3 were listed at risk for serious TEAEs and 0 were reported with serious TEAEs; for other TEAEs, 3 were listed at risk and 2 were reported with events. In the ASN51 low-dose group, the corresponding counts were 3 at risk and 0 with serious TEAEs, and 3 at risk and 0 with other TEAEs. In the ASN51 medium-dose group, 1 was listed at risk for each category, with 0 serious TEAEs and 1 other TEAE. In the ASN51 high-dose group, 1 was listed at risk for each category, with 0 serious TEAEs and 0 other TEAEs. The record reports 0 deaths.

These are descriptive counts, not estimates from a randomized comparison. The study was sequential, and the dose groups should not be treated as directly comparable control groups. The counts do not establish the cause of an event. The registry record does not report specific event terms in the available safety information, and it does not provide detail on event duration or severity. A reported count of 0 serious TEAEs describes the recorded observations in this study; it does not establish that serious events cannot occur.

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

The study is relevant as an early investigation of how ASN51 exposure relates to a brain PET measure in healthy adult participants. Its primary outcome was frontal-lobe VT of [18F]-IMA601 at each scan, and its secondary outcomes included plasma concentration at post-dose PET scans and estimated O-GlcNAcase receptor occupancy. The registry record describes the measurements and schedule, but it does not report the numerical results needed to characterize the observed relationship.

This means the posted information does not establish whether VT changed after dosing, how large any change was, or how closely plasma concentration corresponded to estimated occupancy. It also does not provide a confidence interval or other uncertainty measure. Without those results, neither the magnitude nor the precision of the principal scientific finding can be assessed.

The design further defines the scope of interpretation. This was an open-label, sequential study with no randomized comparator. It can be described as a study of PET measurements and ASN51 exposure in its enrolled participants, but the record does not support a causal comparison between low, medium, and high dose. Differences in timing and sequential exposure are relevant features, and the registry record does not report an analysis addressing them.

The safety information records no serious TEAEs in the displayed groups and reports other TEAEs in the all-participants and medium-dose groups. These counts are descriptive and arise from a small early-phase study. They are not a comprehensive estimate of the frequency of adverse events in a broader population.

In general, the absence of a reported statistical result should not be interpreted as evidence that an effect or relationship was absent. It indicates that the registry record does not report enough quantitative information to judge the result. The study’s intended question is clear, but its numerical answer and statistical precision are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a study objective and a reported result. The stated objective was to examine the relationship between plasma concentration and brain target occupancy after oral ASN51. The endpoint descriptions explain how PET and plasma measurements were intended to contribute to that question. Yet the registry record does not report numerical VT values, occupancy estimates, or an estimated concentration–occupancy relationship. A clear scientific aim does not by itself provide evidence about the size or precision of an observed association.

The sequential structure also matters. PET measurements across baseline and post-dose scans can provide repeated information within participants, but observations collected at different times and after different dose sessions require careful interpretation. General statistical practice would consider repeated-measure dependence, timing, and the way the exposure relationship is modeled. The registry record does not describe whether or how these issues were addressed.

The study also demonstrates why dose labels should not be mistaken for randomized comparison groups. The record lists low, medium, and high doses, but allocation is not applicable and the design is sequential. A statistical contrast between those categories would require a design and analysis rationale that is not reported in the registry record.

Finally, the record lists 16 outcome measures but 0 analyses. It does not report a statistical plan, inferential results, missing-data procedures, or multiplicity handling. Those details matter because they establish which questions were prioritized and how uncertainty was evaluated. For readers, distinguishing measured outcomes from analyzed results is essential: the record documents what the study intended to assess, while the numerical evidence needed to judge the principal relationship is not reported.

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 gives limited information for interpreting the primary endpoint. It describes participant-wise frontal-lobe VT measurements at PET scans but does not report the values, the change from baseline, or an estimated relationship with ASN51 concentration. No confidence interval, p-value, or model-based result is reported. This prevents assessment of the direction, magnitude, or precision of the primary finding.

The study enrolled 3 healthy adult participants and used an open-label, sequential design without a randomized comparison. The dose categories are not like-for-like control groups, and the record does not explain an approach to separating dose effects from order, timing, or participant differences. The scan schedule also describes different PET Scan 2 timing for participant 1 compared with participants 2 and 3. How the timing differences were handled analytically is not reported in the registry record.

The registry record does not report participant characteristics beyond describing the population as healthy adults. It does not provide detailed information about the dose levels, dose-order rationale, the PET measurement model, or the statistical model used to estimate target occupancy. Missing observations and reasons for missingness are not reported. Neither a statistical analysis plan nor multiplicity procedures are described.

Safety interpretation is also limited to descriptive counts. The available record does not provide specific non-serious event terms or sufficient detail to characterize event timing, severity, or attribution. The small enrollment and lack of a randomized control group constrain comparisons. These limitations mean the registry record supports a description of the study’s intent and recorded safety counts, but not a broad estimate of treatment effects or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Brain Target Occupancy of ASN51 — NCT06390098.
• Registry record last updated 2025-05-08; status last verified 2025-05.
• Results first posted 2025-05-08.
• 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

NCT06390098 was a completed Phase 1, open-label, sequential PET study in healthy adult participants, sponsored by Asceneuron S.A. The registry record reports an enrollment of 3, a start date of 2021-08-09, and a primary completion date of 2021-10-12. Participants received low, medium, and high doses of oral ASN51 in the described imaging sessions.

The primary outcome was regional frontal-lobe VT of [18F]-IMA601 at each brain scan. Secondary outcomes included TEAEs, laboratory and clinical safety measures, ASN51 plasma concentration, and estimated O-GlcNAcase receptor occupancy. The registry record lists 16 outcome measures and 0 analyses. It reports descriptive safety counts, including 0 serious TEAEs in the displayed groups, but numerical primary-endpoint results and the concentration–occupancy relationship are not reported in the registry record.