A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function (NCT06568861), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration Time Curve [AUC].

2. Clinical Question

3. Trial Design

This is a Phase 1, non-randomized, open-label, multiple-dose, parallel-group study of ALG-097558. It enrolled subjects with moderate hepatic impairment and subjects with normal hepatic function. The registry lists an enrollment of 16 and a status of completed. The recorded start date is 2025-01-13, and the primary completion date is 2025-07-16.

The two groups received the same stated regimen: oral ALG-097558 at 200 mg twice daily, every 12 hours, for 6 days and 11 total doses. The normal-function group was demographically matched to the impaired-function group for age and body weight and, to the extent possible, gender. This matching may improve comparability on those characteristics, but it does not make the groups randomized or remove the possibility of other differences between them.

With no random allocation and no masking, participants and study personnel were not assigned or kept unaware of group status through those methods. The parallel-group structure means the groups were followed as separate cohorts rather than as a crossover in which each subject receives both conditions. The study’s stated primary purpose is to characterize the effect of hepatic impairment on plasma pharmacokinetics following multiple dosing.

The primary outcome concerns AUC for ALG-097558 and metabolite ALG-097730. A secondary outcome concerns the incidence of treatment-emergent adverse events. The registry lists seven outcome measures and zero analyses. Detailed statistical methods, including the planned comparison and any adjustment strategy, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: During the study a total of 20 participants were screened. 16 participants were enrolled in the study. All 16 participants received the study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: In case of missing observations, the 'Number of Participants Analyzed' represents the number of non-missing observations.

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 Area Under the Concentration Time Curve [AUC], measured over AUC(0-12): Pre-dose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12h post last dose on days 1 and 6; AUC(0-last): Predose (-0.75), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12h post last dose on day 1 and 6, and additionally 14, 24, 36 and 48h on day 6 only.

The primary endpoint is area under the concentration-time curve, or AUC, for ALG-097558 and metabolite ALG-097730 in plasma. AUC represents drug exposure over a stated interval by accounting for measured concentrations across time, rather than relying on a single concentration measurement. It is used in pharmacokinetic studies to describe how much drug is present in the body over an interval after administration.

The record identifies AUC(0-12) and AUC(0-last). For AUC(0-12), samples are specified from pre-dose through 12 hours after the last dose on days 1 and 6. For AUC(0-last), the schedule includes those sampling times on days 1 and 6, with additional times of 14, 24, 36 and 48 hours on day 6 only. These schedules define the intervals and sampling points relevant to the endpoint; they do not, by themselves, indicate the measured exposure in either group.

The endpoint is summarized using a geometric mean and geometric coefficient of variation. A geometric mean is a way to summarize positive, often right-skewed measurements on a multiplicative scale. The geometric coefficient of variation describes relative spread on that scale. These summaries can characterize exposure and variability, but they do not replace a reported between-group estimate or its uncertainty. Numerical AUC results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies AUC as the primary pharmacokinetic endpoint and specifies a geometric mean with geometric coefficient of variation. It does not report a detailed statistical analysis plan, a model for comparing groups, confidence intervals, or numerical results. The concepts below are general explanations of the stated summaries and of how such results are commonly interpreted; they are not claims about methods used in this study unless explicitly identified in the registry record.

What does AUC measure?

In general, AUC summarizes concentration over time. Repeated blood samples describe the concentration-time profile, and the area under that profile represents exposure over the defined interval. AUC(0-12) refers to exposure across the interval ending 12 hours after dosing. AUC(0-last) uses the recorded sampling schedule through the last specified collection time. The record gives sampling times for these endpoints on days 1 and 6, with additional later collections for AUC(0-last) on day 6. Sampling schedules define how exposure is observed; they do not disclose the resulting AUC values.

Why use a geometric mean?

As a general statistical approach, a geometric mean is useful for positive measurements that vary multiplicatively or have a right-skewed distribution. It is calculated on a logarithmic scale and expressed back on the original scale. In pharmacokinetics, this can provide a representative summary when a few relatively large measurements would pull an arithmetic mean upward. The geometric mean is not the same as the median and should not be interpreted as describing every participant’s exposure.

The geometric coefficient of variation is a measure of relative spread associated with geometric-scale data. In general, it helps describe how variable observations are in relation to the scale of their values. It is a descriptive measure, not an uncertainty interval for the group mean and not a test of whether groups differ. The registry names this dispersion statistic but does not report its value.

How would a group comparison be interpreted?

For positive pharmacokinetic measurements, comparisons are often made on a log scale and expressed as a ratio after transformation back to the original scale. In general, a ratio describes relative exposure: a value of 1 would indicate equal point estimates, while values on either side would indicate a relative difference. No ratio, group contrast, or confidence interval is reported in the registry record, so no such interpretation can be made for this study.

A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. In general, it communicates precision as well as the estimated effect: a narrower interval indicates greater precision than a wider interval, all else equal. It does not guarantee that the true value lies within the particular interval. The confidence level and any interval for the primary endpoint are not reported in the registry record.

Why does the design matter?

Randomization can help balance measured and unmeasured characteristics across groups on average. This study is non-randomized, and the groups were matched on age and body weight and, as far as possible, gender. In general, matching can address selected characteristics, but it cannot ensure balance on every relevant feature. A between-group difference in a non-randomized study may reflect hepatic function, other group differences, or both. The registry does not report an adjusted analysis that could clarify this issue.

The study is open-label, so masking was not used. For objective concentration measurements, the absence of masking does not change the definition of AUC, but it may matter for outcomes that involve judgment or reporting. No conclusions about such effects can be drawn from the design description alone. The parallel-group structure also means that the comparison is between separate groups, not a within-subject contrast.

What can planning calculations tell readers?

In general, sample-size calculations estimate the number of participants needed under specified assumptions about an effect, variability, significance level, allocation, and statistical model. The planning assumptions described for this study use the observed effect as a basis and include a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are planning calculations, not observed power and not evidence that the study detected an effect. The registry record does not report its own design justification or sample-size rationale. Because numerical primary results are not reported, the planning illustrations cannot be used to infer the observed pharmacokinetic contrast.

What remains unavailable?

The record lists zero analyses and does not report endpoint estimates, confidence intervals, p-values, a statistical model, covariate adjustment, or a multiplicity procedure. It also does not report whether analyses were prespecified in a separate protocol or how departures from any plan were handled. Those omissions limit assessment of the inferential approach. The described endpoint and summaries explain what was intended to be measured, but they are not a substitute for the analysis results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary AUC outcome and a secondary outcome concerning the incidence of treatment-emergent adverse events. It lists zero analyses. A statistical plan specifying how multiple outcomes or multiple AUC measures were handled is not reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently unusual result when no adjustment or hierarchy is used, but the record does not establish which inferential procedures, if any, were planned or performed.

The primary outcome description covers AUC(0-12) and AUC(0-last), as well as plasma pharmacokinetic parameters for ALG-097558 and metabolite ALG-097730. The record does not state how these measures were prioritized for statistical testing, whether they were analyzed separately, or how conclusions across them would be combined. It also does not report p-values or confidence intervals that would allow readers to assess statistical evidence or precision.

The missing-observation note says that the number of participants analyzed represents the number of non-missing observations when data are missing. This clarifies how the analysis count is defined, but does not describe the frequency or pattern of missing data, the reasons for missing observations, or any imputation method. Endpoint-specific analysis counts are not reported in the registry record.

The analysis populations, including any safety or pharmacokinetic analysis-set definitions beyond the stated non-missing-observation rule, are not reported in the registry record. The registry record also does not report a detailed statistical plan, interim analyses, or procedures for handling protocol deviations. These gaps make it difficult to evaluate how complete the analysis was or how the reported estimates, if available, would relate to the planned analysis.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: alcohol withdrawal syndrome (12.5%), hepatitis alcoholic (12.5%).

The safety listing reports serious adverse events and other adverse events separately for the two groups. Among subjects with moderate hepatic impairment, 1 of the 8 listed at risk had a serious adverse event; among subjects with normal hepatic function, 0 of the 8 listed at risk had a serious adverse event. For other adverse events, the listing records 1 of 8 at risk in each group. It records 0 deaths in both groups.

The registry also lists Alcohol Withdrawal Syndrome and Hepatitis alcoholic as top serious-event terms, each with a reported percentage of 12.5%. The term listing does not provide group attribution in the information recorded here, so these percentages should not be assigned to a particular group based on the available record. The counts and terms are descriptive; they do not establish a difference in risk or a causal relationship to treatment.

These safety figures should be read in the context of a non-randomized study with a limited number of subjects. They do not convey event timing, duration, severity beyond the serious-event classification, or a statistical comparison. Treatment-emergent adverse events are a stated secondary outcome, but a fuller outcome analysis is not reported in the registry record.

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

This trial addresses a focused pharmacokinetic question: whether plasma exposure to ALG-097558 and its metabolite ALG-097730 differs between subjects with moderate hepatic impairment and subjects with normal hepatic function after the stated multiple-dose regimen. It also records safety and tolerability as study objectives. The registry supplies the endpoint definitions, sampling schedule, group descriptions, and selected adverse-event counts.

What the record does not establish is the actual size or direction of a pharmacokinetic difference. Numerical AUC estimates, a between-group contrast, and uncertainty intervals are not reported in the registry record. Without those results, readers cannot determine whether the observed exposure was higher, lower, or similar between groups, or how precisely any difference was estimated. The endpoint description is not itself a result.

The study design also constrains interpretation. Because allocation was non-randomized, the groups may differ in characteristics other than hepatic function. Matching on age and body weight and, as far as possible, gender addresses selected factors but does not remove all potential confounding. Any group contrast would therefore be descriptive of the study cohorts unless supported by further design and analysis details, which are not reported in the registry record.

The listed adverse-event counts provide a limited account of safety observations. They are not a formal comparative analysis and should not be treated as proof of equivalence or difference between groups. The registry does not give enough detail to interpret event timing, exposure-adjusted rates, or the full clinical context of the listed terms.

In statistical terms, the record clarifies what was measured and how some outcomes were summarized, but does not report the primary numerical findings needed to assess effect magnitude and precision. The study’s completed status does not fill that reporting gap. Its conclusions cannot be reconstructed from the design, endpoint definition, or safety counts alone.

13. Why This Trial Matters Statistically

Hepatic function is the central grouping characteristic in this pharmacokinetic study. Measuring exposure in subjects with moderate hepatic impairment alongside a group with normal hepatic function addresses a question that differs from a conventional efficacy comparison: the focus is how a defined clinical characteristic relates to drug concentration over time under a stated regimen.

The design illustrates why understanding the estimand and the comparison matters. The primary outcome is AUC, summarized geometrically, while the groups are non-randomized and matched on selected demographic characteristics. The resulting comparison, if fully reported, would need to be interpreted as a comparison of these cohorts rather than automatically as a causal effect of hepatic impairment. The design can be informative while still leaving room for confounding.

The record also makes the distinction between measurement plans and statistical findings important. It specifies sampling times and AUC intervals, and identifies a geometric mean and geometric coefficient of variation. These details help readers understand the intended pharmacokinetic summaries. They do not reveal the group values, the uncertainty around them, or whether any contrast was precise.

Finally, the record demonstrates the value of complete statistical reporting. Without the numerical primary results, analysis populations, and comparison method, readers cannot evaluate the size or reliability of the central finding. The study question and design are clear, but a statistical interpretation of the primary outcome requires results that are not reported in the registry record.

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 most consequential limitation of the available record is the absence of numerical primary pharmacokinetic results. Although the endpoint, analytes, summaries, and sampling schedule are described, AUC estimates and a between-group comparison are not reported in the registry record. This prevents assessment of effect direction, magnitude, and precision.

The non-randomized design limits causal interpretation. Matching was described for age and body weight and, to the extent possible, gender, but other differences between groups may remain. The registry does not report an adjusted analysis or enough detail to assess how potential confounding was addressed. Open-label conduct is also recorded, with no masking.

The record lists an enrollment of 16 and adverse-event risk sets of 8 in each group. It does not report endpoint-specific analysis counts or describe the extent and pattern of missing observations. The note defining analyzed participants as those with non-missing observations does not explain why data may be missing or how missingness was handled analytically.

Further limitations include the lack of a reported statistical analysis plan, inferential model, confidence intervals, p-values, or multiplicity approach. The adverse-event information is limited to selected counts and serious-event terms, without a fuller account of timing or group attribution for the listed terms. These omissions constrain interpretation of both the primary endpoint and safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function — NCT06568861.
• Registry record last updated 2026-08-05; status last verified 2026-05.
• Results first posted 2026-08-05.
• 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

NCT06568861 is a completed Phase 1, non-randomized, open-label, parallel-group study of ALG-097558 in subjects with moderate hepatic impairment and subjects with normal hepatic function. The registry lists enrollment of 16. Both groups received 200 mg orally twice daily for 6 days and 11 total doses; the groups were matched for age and body weight and, to the extent possible, gender.

The primary outcome is plasma AUC for ALG-097558 and metabolite ALG-097730, summarized using a geometric mean and geometric coefficient of variation. A secondary outcome concerns treatment-emergent adverse events. The registry lists seven outcome measures and zero analyses, but numerical primary pharmacokinetic results and a detailed statistical plan are not reported in the registry record.

The adverse-event listing records serious events in 1 subject in the impaired-function group and none in the normal-function group, other adverse events in 1 subject in each group, and no deaths. These are descriptive counts, not a comparative safety analysis.