STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT (NCT04604496), a non-randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

3. Trial Design

The registry describes a Phase 1, non-randomized, open-label, single-dose, parallel cohort study. It enrolled 24 participants and is listed as completed. The recorded start date is 2020-12-30, and the primary completion date is 2022-01-10. Pfizer is listed as the sponsor.

Four cohorts are identified: participants without hepatic impairment and participants with mild, moderate, or severe hepatic impairment. Each cohort was to receive an oral dose of PF-06882961 20 mg on Day 1. Because allocation was non-randomized, the groups were defined by impairment status rather than by a random assignment process. The registry explicitly cautions that the arms are not a like-for-like control comparison. Differences between cohorts could therefore reflect group characteristics as well as hepatic impairment.

The study is described as open-label in its official title. The masking entry is recorded as single, but the identity of anyone masked is not reported in the registry record. The parallel-cohort design means that participants were studied in separate groups rather than being described as crossing between impairment categories.

The primary endpoint was Cmax, the maximum observed plasma concentration of PF-06882961. The secondary outcomes include treatment-emergent adverse events, clinical laboratory abnormalities, categorical vital-sign data, and categorical electrocardiogram data. The registry lists 8 outcome measures and 12 analyses, but the numerical pharmacokinetic results are not reported in the record. Protocol details beyond the listed design features, including a sample-size justification and any interim analyses, 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: A total of 29 participants were screened in the study, among whom, 24 participants were treated with PF-06882961 (Danuglipron).

Open Label Treatment

Follow-Up

Analysis population for the primary outcome, as defined in the registry: The analysis population refers to all participants who received at least 1 dose of PF-06882961 and had at least 1 of the pharmacokinetic (PK) 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.

Population: The baseline analysis population included all participants enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax), measured over Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1..

Cmax is the maximum observed concentration of PF-06882961 in plasma over the observation period. The registry defines it as the maximum observed plasma concentration and reports it using a geometric mean, with geometric coefficient of variation as the dispersion measure. Samples were scheduled at predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.

As a general pharmacokinetic concept, a peak concentration describes the highest measured concentration during a specified sampling period. It is useful for comparing peak levels between groups, but it does not by itself describe the entire concentration-time profile or total drug exposure. The sampling schedule determines which observed concentration can be identified as the maximum; a peak between scheduled measurements may not be directly observed.

The geometric mean is a measure suited to positive values that can vary multiplicatively. The geometric coefficient of variation describes dispersion on a relative, rather than simple additive, scale. These summaries can help describe concentration data, but the registry record does not report the cohort-specific Cmax values, their dispersion, or the estimates comparing impairment cohorts with the reference cohort. The size and precision of any observed difference therefore cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a geometric mean for the primary Cmax endpoint and a geometric coefficient of variation for dispersion. The numerical endpoint results and the comparisons between cohorts are not reported in the registry record. The methods below explain the statistical concepts named by the design; they do not establish which additional analyses were performed.

Why use a geometric mean?

As a general statistical concept, a geometric mean summarizes positive measurements on a multiplicative scale. It is calculated by averaging values after taking logarithms and then returning to the original scale. This can be useful when measurements vary in relative terms, rather than by a similar fixed amount, and when the distribution is asymmetric. Plasma concentrations are positive measurements, so a geometric summary can be a practical way to describe them. The registry does not report whether the observed concentration data followed any particular distribution.

A geometric mean is not the same as an arithmetic mean. It emphasizes proportional relationships, and a comparison based on geometric means is naturally interpreted in terms of relative levels. No cohort-specific means, estimated contrasts, or confidence intervals are reported, so the magnitude and precision of any such comparison cannot be assessed.

What does the geometric coefficient of variation describe?

As a general concept, a coefficient of variation expresses dispersion relative to a central value. The geometric version is designed for data handled on a logarithmic scale. It describes how variable observations are in proportional terms, rather than expressing spread in the original measurement units. A larger dispersion indicates more variability among measured concentrations, but does not by itself establish whether group averages differ.

Dispersion and uncertainty about an estimated group summary are distinct. A coefficient of variation describes spread in the measurements; a confidence interval, if reported, would convey uncertainty about an estimate under the analysis assumptions. The registry record does not report confidence intervals for Cmax or a numerical geometric coefficient of variation.

Why does the sampling schedule matter?

Cmax is defined as the maximum observed concentration, so it depends on the measurements collected over time. The planned schedule begins at predose (0 hours) and includes measurements through 48 hours post dose on Day 1. More frequent sampling can offer a finer view of a concentration profile, while less frequent sampling can miss a peak that occurs between scheduled measurements. This is a general measurement issue, not evidence that a peak was missed in this study. The registry does not provide individual concentration profiles or enough detail to assess how closely the observed maximum tracked each participant’s true peak.

How should the cohort comparisons be read?

The design compares separate groups defined by hepatic impairment status. Since allocation was non-randomized, measured and unmeasured differences between participants could be associated with both group membership and pharmacokinetic outcomes. Randomization is one method for balancing such characteristics on average; it was not used. The record does not describe adjustment methods or covariates, so it is not possible to say whether the reported analyses adjusted for participant characteristics.

Four cohorts create more than one possible comparison with the group without impairment. Multiple comparisons can raise the chance of finding an apparently notable result when many hypotheses are tested. Whether and how this issue was addressed is not reported in the registry record. No p-values, confidence intervals, or numerical comparison estimates for the primary endpoint are reported.

The registry also includes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not the trial’s design justification, and no numerical planning estimates are reported in the registry record. They should not be interpreted as observed power or as evidence about the precision of the study’s findings.

In general, over-dispersion means that observed variability is greater than a model assumes. If present and ignored, it can make standard errors and inferential conclusions unreliable. The registry does not report an over-dispersion assessment or identify a model for the primary analysis, so no claim can be made about whether this issue arose. The same restraint applies to any analysis choice not explicitly described in the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 12 analyses. The primary endpoint is Cmax; the secondary outcomes include treatment-emergent adverse events, clinical laboratory abnormalities, categorical vital-sign data, and categorical electrocardiogram data. Multiple endpoints, cohorts, and possible pairwise comparisons can create multiplicity: the more hypotheses examined, the greater the chance that at least one result appears notable by chance. Whether the study prespecified a testing hierarchy, adjusted for multiple comparisons, or treated analyses as descriptive is not reported in the registry record.

The record defines the pharmacokinetic analysis population as participants who received at least 1 dose of PF-06882961 and had at least 1 of the pharmacokinetic parameters of interest calculated. The number of participants meeting this definition and the handling of participants without usable measurements are not reported in the registry record. The population used for each safety outcome is also not described beyond the at-risk counts shown for the adverse-event groups.

Missing concentration measurements could affect the observed maximum or the ability to calculate a pharmacokinetic parameter. As a general statistical point, methods for handling missing observations should be clear because different approaches can change which participants contribute to an analysis and how results are interpreted. The missing-data rules, reasons for missingness, and any sensitivity analyses are not reported in the registry record.

Details of the statistical analysis plan, including any adjustment for multiplicity and missing data, are not reported in the registry record. The numerical primary outcome results are also absent, which prevents examination of the estimates, their uncertainty, and the extent of data contributing to them.

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 reports serious adverse-event counts separately from other adverse-event counts for four cohorts. The at-risk count is 6 in each cohort. Serious adverse events are listed as 0 in the group without hepatic impairment and 0 in each of the mild, moderate, and severe impairment groups. Deaths are listed as 0 in every group.

For other adverse events, the record lists 0 participants in the group without impairment, 1 in the mild impairment group, 2 in the moderate impairment group, and 1 in the severe impairment group. These are participant counts, not event counts or rates, and the registry does not provide further detail about the events in these figures. The listed secondary safety outcomes also include clinical laboratory abnormalities, categorical vital-sign data, and categorical electrocardiogram data; their numerical results are not reported in the registry record.

Zero serious events in the posted counts means none were recorded in these groups in the registry results. It does not establish that an event is impossible or that groups have equivalent safety. With small at-risk groups and no comparative uncertainty estimates reported, differences in counts should be read descriptively rather than as precise comparative evidence.

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

This trial addresses a pharmacokinetic question: whether peak plasma concentrations of PF-06882961 differ across groups with varying degrees of hepatic impairment compared with participants without impairment. It is a Phase 1, non-randomized, open-label study of a single oral dose. The registry identifies Cmax as the primary endpoint and specifies how it was measured, but numerical Cmax results are not reported in the registry record.

Without the endpoint estimates and their dispersion or uncertainty, the direction, size, and precision of any cohort differences cannot be evaluated. The registry’s stated objective of examining clinical meaningfulness does not substitute for a reported result, and the record does not state the threshold used to define a clinically meaningful difference. Nor can the safety counts answer the primary pharmacokinetic question.

The posted adverse-event figures describe the counts recorded for these cohorts: no serious adverse events or deaths are listed, and other adverse events are listed in the mild, moderate, and severe impairment groups. These observations are descriptive. They do not establish equivalence between groups, rule out uncommon events, or quantify a causal effect of impairment on safety.

Because the study was non-randomized, cohort comparisons are not protected by random assignment from differences in participant characteristics. The registry explicitly cautions that the arms are not a like-for-like control comparison. The record does not provide enough information about cohort characteristics or adjusted analyses to assess the influence of such differences.

The study therefore documents a relevant comparison framework and a defined pharmacokinetic endpoint, but the posted record does not permit a numerical conclusion about Cmax or the clinical meaning of any possible difference. Completion status and enrollment alone do not establish that the study demonstrated or excluded an effect.

13. Why This Trial Matters Statistically

Hepatic impairment can be an important consideration in pharmacokinetic evaluation because the study’s central question is whether impairment status is associated with a change in drug concentration after dosing. This trial is statistically informative in its design: it defines a peak concentration endpoint, collects samples at specified post-dose times, and compares several impairment categories with a group without impairment.

The study also illustrates why design and results must be considered together. A defined endpoint can make the question precise, but without reported numerical estimates a reader cannot judge the size or precision of the observed differences. Likewise, a reference cohort helps organize comparisons, but non-randomized assignment means that cohort differences cannot automatically be attributed to impairment status alone.

The distinction between peak concentration and broader exposure is another important statistical point. Cmax captures the highest observed concentration over the sampling schedule. It does not, by itself, summarize the full concentration-time profile. The record’s specified sampling times provide context for how the maximum was observed, but the numerical concentration data are not reported.

Finally, the safety counts underscore the limits of small descriptive groups. Counts can communicate what was recorded, but without comparative estimates, uncertainty, and fuller outcome details they do not establish equivalence or quantify risk. In this case, the posted information supports careful description of the study design and selected event counts, while the central pharmacokinetic result remains unavailable 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 important limitation for interpreting the study’s primary question is that numerical Cmax results are not reported in the registry record. Cohort estimates, measures of dispersion, and uncertainty around comparisons are therefore unavailable. The same record does not report numerical findings for the listed clinical laboratory, vital-sign, or electrocardiogram outcomes.

The non-randomized design limits causal interpretation. Participants were grouped by hepatic impairment status, and the registry explicitly warns that the arms are not a like-for-like control comparison. Cohort characteristics and any adjustment for differences between groups are not reported in the registry record. The open-label description may also be relevant to some outcome assessments, but the record does not describe how outcome assessment was conducted.

The record lists 24 enrolled participants and an at-risk count of 6 for each adverse-event group. These group sizes limit how much can be inferred from event counts, particularly when events are uncommon. The registry provides counts but no uncertainty intervals or comparative safety analyses. It also does not report detailed descriptions of the other adverse events.

The analysis population is defined by receipt of at least 1 dose and calculation of at least 1 pharmacokinetic parameter, but the number meeting that definition and the treatment of missing observations are not reported. The statistical analysis plan, multiplicity strategy, and sample-size justification are also not reported in the registry record. The listed planning assumptions do not establish the rationale for the trial’s enrollment or resolve uncertainty about the missing outcome results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT — NCT04604496.
• Registry record last updated 2024-03-21; status last verified 2023-09.
• Results first posted 2024-03-21.
• 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.

18. Record Summary

This completed Phase 1 study examined PF-06882961 pharmacokinetics in adults with mild, moderate, or severe hepatic impairment and participants without hepatic impairment. The non-randomized, open-label, single-dose, parallel cohort design included an oral dose of PF-06882961 20 mg on Day 1, with an enrollment of 24.

The primary endpoint was maximum observed plasma concentration, measured on a scheduled sampling period through 48 hours post dose on Day 1 and summarized using a geometric mean and geometric coefficient of variation. The registry lists safety outcomes covering adverse events, laboratory abnormalities, vital signs, and electrocardiogram data.

The posted safety counts list no serious adverse events or deaths in any cohort. Other adverse events are listed for participants in the mild, moderate, and severe impairment groups. Numerical pharmacokinetic results and further numerical safety findings are not reported in the registry record, so the primary comparison’s size and precision cannot be assessed.