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 Compare How the Study Medicine (PF-07923568) is Processed in Participants With Different Levels of Loss of Liver Function to Healthy Participants. (NCT05857644), a non-randomized phase 1 study. The primary outcome is Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05857644 |
| Phase | Phase 1 |
| Condition | Liver Diseases, Hepatic Impairment |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
The study asks how the body processes a single oral dose of PF-07923568 in adults with different levels of hepatic impairment compared with adults without hepatic impairment. Its primary pharmacokinetic measure is the maximum observed plasma concentration of sisunatovir, or Cmax. Comparing this measure across the groups is intended to characterize whether observed peak concentrations differ by hepatic-function group.
Population
Adults who were healthy, or who had mild, moderate, or severe hepatic impairment. The primary-outcome population is described as participants who received at least one dose of sisunatovir and had at least one pharmacokinetic parameter of interest calculated.
Intervention
A single oral dose of PF-07923568, described in the arm summaries as four capsules. The primary outcome names the drug as sisunatovir.
Comparator
Participants without hepatic impairment are the reference group for comparison with participants in the mild, moderate, and severe hepatic-impairment groups. Allocation was non-randomized, so these groups are not randomized treatment arms.
Primary question
What is the maximum observed plasma concentration of sisunatovir after the single oral dose in each hepatic-function group, and how does that measure compare across groups? The registry record does not report the group Cmax estimates or their comparisons.
This is a pharmacokinetic question, not a comparison of clinical benefit. Cmax describes a peak concentration measured after dosing; it does not, by itself, describe the full concentration-time profile or establish a clinical consequence. The outcome was assessed using samples collected from Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6. The registry record also lists safety and tolerability outcomes, including adverse events, laboratory abnormalities, vital signs, and electrocardiograms.
3. Trial Design
This was a phase 1, open-label, single-dose, parallel-group study with non-randomized allocation and no masking. It enrolled 28 participants, and the registry record gives its status as completed. The study began on 2023-06-07, with primary completion on 2024-02-07. The sponsor was Pfizer.
The parallel groups were defined by hepatic function: no impairment, mild impairment, moderate impairment, and severe impairment. Each group description specifies a one-time oral dose of four capsules of PF-07923568. Participants with hepatic impairment were compared with healthy participants without hepatic impairment. Because assignment was non-randomized, the group comparison is observational with respect to hepatic-function status; it is not a randomized comparison of impairment levels.
The stated primary outcome was plasma maximum concentration, Cmax, of sisunatovir following a single oral dose. The outcome description defines Cmax as the highest concentration observed directly from data. The listed sampling schedule runs from Hour 0 through Hour 120 postdose, across Day 1 to Day 6. The primary-outcome population includes participants who received at least one dose and had at least one pharmacokinetic parameter of interest calculated.
The study description says participants were to undergo screening for up to 28 days and remain at the study clinic for 6 days after admission. It describes a follow-up contact about 28 to 35 days after discharge. These procedural details do not specify how pharmacokinetic measurements were statistically compared. The statistical analysis plan, including the model used for the primary comparison, is not reported in the registry record.
The record lists 7 outcome measures and 9 analyses. It does not reduce the study to one comparison. The reported design therefore needs to be read as a set of group-based pharmacokinetic and safety assessments rather than as a blinded, randomized efficacy trial.
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
| Stage | No Hepatic Impairment | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 4 |
| COMPLETED | 8 | 8 | 8 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of sisunatovir and had at least 1 of the pharmacokenetic parameters of interest calculated.
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 | No Hepatic Impairment | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 8 | 8 | 8 | 4 | 28 | |
| Age, Customized: 18-44 years | Participants | 0 | 1 | 1 | 0 | 2 |
| Age, Customized: 45-64 years | Participants | 7 | 3 | 6 | 2 | 18 |
| Age, Customized: ≥65 years | Participants | 1 | 4 | 1 | 2 | 8 |
| Sex: Female, Male: Female | Participants | 4 | 3 | 4 | 1 | 12 |
| Sex: Female, Male: Male | Participants | 4 | 5 | 4 | 3 | 16 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 1 | 3 | 3 | 3 | 10 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 7 | 5 | 5 | 1 | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Maximum Concentration (Cmax) of Sisunatovir Following Administration of a Single Oral Dose, measured over Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | Nanograms/milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is plasma Cmax of sisunatovir after a single oral dose. Cmax is the highest concentration observed directly from the collected measurements. It summarizes the peak observed plasma exposure during the sampling period, which is relevant to describing how the drug appears in circulation after dosing.
The registry record specifies the geometric mean as the summary parameter and the geometric coefficient of variation as the measure of dispersion. A geometric mean is useful for positive concentration measurements when variation is more naturally understood proportionally than as an additive difference. The geometric coefficient of variation describes spread on a relative scale; it is not a confidence interval and does not, by itself, indicate the precision of a group comparison.
Samples were scheduled at Hours 0, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, and 120 postdose from Day 1 to Day 6. The maximum is selected from the observed concentration data, so it is a peak over the observed sampling schedule rather than a direct measurement at every possible moment after dosing.
Cmax is one part of pharmacokinetic characterization. It does not summarize all exposure over time, and the registry record does not report a Cmax estimate, its uncertainty, or a between-group comparison. Those missing results prevent quantitative interpretation of how peak concentrations differed among the hepatic-function groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies Cmax as the primary pharmacokinetic outcome but does not report the group-specific Cmax estimates, geometric coefficients of variation, confidence intervals, or statistical tests. As a result, the direction and magnitude of any difference in peak concentration among the no-impairment, mild, moderate, and severe groups are not reported in the registry record. No conclusion about the size or precision of a pharmacokinetic difference can be drawn from the information recorded for this outcome.
The study's structure is relevant to interpretation. It was open-label and non-randomized, with parallel groups defined by hepatic-function status. The comparison with healthy participants is therefore not a randomized treatment contrast. Differences between groups cannot automatically be attributed to hepatic impairment alone; the registry record does not report whether or how other participant characteristics were accounted for in the analysis.
The endpoint measures a peak concentration during the stated sampling window. It is not a measure of total drug exposure, and the Cmax description does not establish how concentrations changed over the full period after dosing. Other pharmacokinetic parameters may have been assessed, but the registry record does not provide their results in the registry record described for this analysis.
The posted safety counts describe serious adverse events and other adverse events by group. No serious adverse events or deaths are recorded in the listed groups. Other adverse events are recorded in the no-impairment, moderate-impairment, and severe-impairment groups, and none are recorded for the mild-impairment group. These counts are descriptive. They do not establish that a group has a higher or lower risk, particularly because the study is small and non-randomized and the registry record does not give comparative safety estimates or uncertainty intervals.
The registry record says the study is completed, but completion status is not a substitute for numerical endpoint results. A planned sample-size illustration, if considered alongside these results, would be a planning calculation rather than observed power. It cannot fill in unreported primary-outcome estimates or establish the precision of this study's findings.
Overall, the record establishes the question, design, outcome definition, and selected safety counts. It does not report the primary pharmacokinetic results needed to describe the observed Cmax pattern across groups. Interpretation should therefore remain limited to what the record states, rather than treating the study objective as a result.
9. Statistical Methods Explained
The main statistical issue is how a peak concentration is summarized and compared across groups. The registry record specifies a geometric mean for Cmax and a geometric coefficient of variation for dispersion. It does not report the detailed analysis method, estimates, uncertainty intervals, or test results. The explanations below describe general statistical principles; they are not a description of an unreported analysis plan.
Why use a geometric mean?
Concentration measurements are positive, and their variation may be more naturally expressed proportionally than as an additive amount. A geometric mean summarizes the central tendency on a multiplicative scale. In general, this can be useful when a similar proportional change is meaningful across low and high values. It differs from an arithmetic mean, which summarizes values on an additive scale.
A geometric mean does not show every participant's measurement or the range of values. It is a summary of the group distribution, so it should be read alongside a measure of variability and, for comparisons, an estimate of uncertainty. The registry record identifies a geometric coefficient of variation as the dispersion measure but does not give the group values.
What does the coefficient of variation describe?
In general, a coefficient of variation expresses variability relative to a central value. A geometric coefficient of variation is suited to describing proportional dispersion for measurements summarized geometrically. It is not a confidence interval. A confidence interval addresses uncertainty in an estimate, whereas a coefficient of variation describes variation among observations under the relevant calculation. The registry record does not report a confidence interval for Cmax or explain the inferential procedure used.
Why does the sampling schedule matter?
Cmax is defined as the highest concentration observed directly from data. The observed maximum depends on the measurements collected and their timing. The schedule in this study includes samples from Hour 0 through Hour 120 postdose, from Day 1 to Day 6. In general, a peak that occurs between scheduled samples may not be captured at its exact time; the endpoint as described is the maximum observed in the collected data. The record does not report a separate estimate of an unobserved peak.
How should group comparisons be understood?
In general, a comparison of group summaries asks whether the observed distributions differ and how precisely that difference is estimated. A confidence interval, when reported, conveys a range of values compatible with the data and analysis assumptions. A test result alone would not show the size of a difference; the estimate and its uncertainty are needed for interpretation. Here, the registry record does not report the group Cmax summaries, comparison estimates, confidence intervals, or test results, so the primary comparison cannot be reconstructed from the record.
The study is non-randomized, and groups are defined by hepatic-function status. In general, randomization helps balance measured and unmeasured characteristics across treatment groups, but it does not apply to this comparison. A non-randomized group contrast can be affected by differences in participant characteristics or other factors. The registry record does not report an adjustment strategy, so it is not possible to say whether any such factors were included in the primary analysis.
Why can over-dispersion matter?
In general, over-dispersion means that observations vary more than a statistical model expects. If a model understates variability, its uncertainty estimates can be too narrow and its tests can appear more decisive than warranted. The appropriate response depends on the outcome and model, and may involve a different variance assumption or another method. The registry record does not report a model for Cmax or indicate whether over-dispersion was assessed. This general concern should not be taken to mean that over-dispersion occurred in this study.
What do planning calculations mean?
Sample-size calculations are planning tools that show what a proposed design might require under stated assumptions. The registry record describes planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event tables, the stated quantity is total events; for other tables, it is participants per arm. Such illustrations are not observed power and do not establish how precisely this completed study estimated Cmax. The specific planning values and the observed effect are not reported in the record details available for this explanation.
The registry record gives the primary-outcome population as participants who received at least one dose and had at least one pharmacokinetic parameter of interest calculated. In general, defining an analysis population is important because exclusions or missing measurements can affect which observations contribute to an estimate. The record does not state how many participants contributed to the primary Cmax analysis or how incomplete concentration profiles were handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 7 outcome measures and 9 analyses. It does not report a multiplicity strategy, such as whether testing across outcomes or hepatic-function groups was adjusted, which comparison was treated as primary for inference, or how any testing hierarchy was specified. Without those details, the false-positive risk across multiple analyses cannot be assessed from the registry record.
The primary-outcome population is described as participants who received at least one dose of sisunatovir and had at least one pharmacokinetic parameter of interest calculated. The record does not state how many participants contributed data to the Cmax analysis, whether all scheduled samples were available, or how missing concentration measurements were handled. It also does not report whether a participant with an incomplete profile could contribute to Cmax estimation.
Missing data can matter when the availability of measurements is related to participant characteristics, safety, or the concentrations being measured. In general, an analysis based only on available observations may be affected if the missingness is not unrelated to the outcome. The registry record does not describe missing-data assumptions, imputation, sensitivity analyses, or exclusions for the pharmacokinetic endpoint.
The outcome definition and population description identify what the analysis was intended to measure, but they do not provide the statistical plan. The methods for handling multiple comparisons and missing data are not reported in the registry record. Consequently, the precision and robustness of any Cmax comparison cannot be evaluated from the recorded information.
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 |
|---|---|---|---|
| No Hepatic Impairment | 0 | 8 | 0.0% |
| Mild Hepatic Impairment | 0 | 8 | 0.0% |
| Moderate Hepatic Impairment | 0 | 8 | 0.0% |
| Severe Hepatic Impairment | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| No Hepatic Impairment | 0 of 8 |
| Mild Hepatic Impairment | 0 of 8 |
| Moderate Hepatic Impairment | 0 of 8 |
| Severe Hepatic Impairment | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| No Hepatic Impairment | 1 of 8 |
| Mild Hepatic Impairment | 0 of 8 |
| Moderate Hepatic Impairment | 1 of 8 |
| Severe Hepatic Impairment | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | No Hepatic Impairment | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 8 | 0 of 8 | 0 of 8 | 0 of 4 |
| Hypokalaemia | Metabolism and nutrition disorders | 0 of 8 | 0 of 8 | 0 of 8 | 1 of 4 |
| Dizziness | Nervous system disorders | 1 of 8 | 0 of 8 | 0 of 8 | 0 of 4 |
| Diarrhoea | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 1 of 8 | 0 of 4 |
The registry record lists serious adverse events, other adverse events, and deaths by hepatic-function group. No serious adverse events are recorded among 8 participants at risk in the no-impairment group, 8 in the mild-impairment group, 8 in the moderate-impairment group, or 4 in the severe-impairment group. No deaths are recorded in any of those groups.
For other adverse events, the record lists 1 among 8 participants at risk with no hepatic impairment, 0 among 8 with mild impairment, 1 among 8 with moderate impairment, and 1 among 4 with severe impairment. These are counts, not comparative risk estimates. No confidence intervals or statistical tests for safety differences are reported in the registry record.
A count of zero means that no event in that category is recorded for the listed group; it does not establish that the underlying risk is zero. The groups are non-randomized and the recorded counts are limited, so apparent differences in counts should not be interpreted as evidence that one group is safer than another. The record also lists secondary safety outcomes involving laboratory abnormalities, vital signs, and electrocardiograms, but their results are not reported in the information.
12. What the Result Does, and Does Not, Mean
This study is designed to characterize pharmacokinetics, specifically the maximum observed plasma concentration of sisunatovir after a single oral dose, across groups with differing hepatic-function status. The record specifies the dose, the sampling schedule, the geometric summary, and the population definition. It also records selected adverse-event counts by group.
The primary question cannot be answered quantitatively from the registry record because the Cmax group estimates and their comparisons are not reported. The record does not show whether peak concentrations were similar or different across the impairment groups, how large any difference was, or how precisely any difference was estimated. The objective of comparing groups is not itself evidence of a particular result.
Even if group Cmax estimates were available, Cmax alone would not describe every aspect of pharmacokinetics. It represents the highest concentration observed during the sampling schedule; it is not a complete description of the concentration-time profile. Nor does a pharmacokinetic summary by itself establish a clinical outcome.
The safety counts provide a limited descriptive account. The record lists no serious adverse events and no deaths in the groups, alongside a small number of other adverse events in some groups. These counts do not establish comparative safety, and they do not replace the unreported results for laboratory tests, vital signs, or electrocardiograms.
The non-randomized, open-label design is important context. Hepatic-function groups were not assigned at random, so the comparison is not a randomized experiment. The registry record does not state whether the analyses adjusted for participant characteristics or how uncertainty was estimated. The study's completed status and its phase designation do not resolve these limitations or supply missing numerical findings.
13. Why This Trial Matters Statistically
Pharmacokinetic studies can help characterize how measured drug concentrations vary across groups with different physiological characteristics. In this study, the groups were defined by hepatic impairment, and the primary measure was the maximum observed plasma concentration after a single oral dose. The sampling schedule and endpoint definition make the target of measurement explicit.
The design also illustrates why a comparator should be interpreted in context. Healthy participants serve as a reference group, but the study used non-randomized allocation. This makes it important to distinguish a descriptive group comparison from a randomized treatment effect. Statistical interpretation depends not only on the endpoint but also on how groups were formed and what adjustments were made.
Reporting the geometric mean and geometric coefficient of variation is relevant to concentration data, where proportional variation can be informative. Yet those summaries are most useful when the actual estimates and appropriate measures of uncertainty are available. The registry record does not report the primary Cmax results, so it does not allow readers to assess the observed pattern or its precision.
The safety counts further show the difference between descriptive reporting and comparative inference. Counts can identify what was recorded in each group, but small, non-randomized group summaries do not establish that observed differences reflect underlying differences in risk. The record's limitations in outcome reporting, missing-data methods, and multiplicity information are therefore central to a careful statistical reading.
The study matters statistically because it poses a clear pharmacokinetic question across clinically defined groups while also demonstrating how design and reporting determine what can be concluded. Its registry description is informative about the intended measurement and study structure, but numerical primary results and analysis details are needed to evaluate the central comparison.
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 principal limitation for interpreting the pharmacokinetic question is that the registry record does not report the primary Cmax estimates or group comparisons. It also does not report uncertainty intervals or test results. The magnitude, direction, and precision of any difference across the hepatic-function groups therefore cannot be assessed.
The comparison is non-randomized and open-label. Participants were grouped by hepatic-function status rather than randomized to those groups. The registry record does not report whether participant characteristics were adjusted for in the analysis, so the extent to which potential differences between groups were addressed is not reported in the registry record.
The endpoint is the highest concentration observed from samples collected at specified times. As a general limitation of observed-peak measures, the value depends on the sampling schedule and may not capture a peak occurring between samples. The record does not report an approach for estimating a peak between scheduled measurements.
The registry record does not report the number contributing to the Cmax analysis, the handling of incomplete concentration profiles, or any missing-data sensitivity analyses. It also does not report a multiplicity strategy despite listing multiple outcomes and analyses. These omissions limit assessment of analysis populations, missingness, and the interpretation of any statistical testing.
Safety information is limited in the record to group counts for serious adverse events, other adverse events, and deaths in the registry record. Comparative estimates and uncertainty are not reported, and results for the listed laboratory, vital-sign, and electrocardiogram outcomes are not reported in the registry record. The available safety counts should therefore be read descriptively.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare How the Study Medicine (PF-07923568) is Processed in Participants With Different Levels of Loss of Liver Function to Healthy Participants. — NCT05857644.
- Registry record last updated 2025-03-21; status last verified 2025-03.
- Results first posted 2025-03-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT05857644, a completed phase 1, open-label, non-randomized, single-dose, parallel-group study sponsored by Pfizer. It enrolled 28 participants and compared healthy participants with groups having mild, moderate, or severe hepatic impairment. Each group was described as receiving one oral dose of four capsules of PF-07923568.
The primary outcome was plasma Cmax of sisunatovir, summarized using a geometric mean and geometric coefficient of variation. Samples were scheduled from Hour 0 through Hour 120 postdose, from Day 1 to Day 6. The record does not report the group-specific Cmax results or statistical comparisons.
Safety listings record no serious adverse events or deaths in the groups and give counts for other adverse events. The record does not report the methods for multiplicity or missing data, nor does it provide comparative safety estimates. The study's findings therefore cannot be quantitatively evaluated for its primary pharmacokinetic question from the registry information described.