A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of PF-06882961 in Chinese Adults With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of PF-06882961 in Chinese Adults With Type 2 Diabetes Mellitus (NCT04889157), a randomized phase 1 study. The primary outcome is AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961.

2. Clinical Question

The study was designed as an 8-week randomized, double-blind, sponsor-open, placebo-controlled Phase 1 trial. Its stated focus was pharmacokinetics, pharmacodynamics, safety, and tolerability in Chinese adults with type 2 diabetes. The primary endpoint is a pharmacokinetic measure, not a direct measure of glucose control or another clinical outcome.

The registry record gives no primary outcome comparison between PF-06882961 and placebo. It lists AUC24 at 40 mg BID on Day 21, 80 mg BID on Day 35, and 120 mg BID on Day 56. Those dose-level observations describe drug exposure at different dose levels and measurement days; they should not be treated as a randomized comparison of dose groups unless the analysis supports that interpretation. Details of the dose allocation and within-participant exposure pattern are not reported in the registry record.

3. Trial Design

This was a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled, parallel study. The registry describes 20 participants enrolled and the study status as completed. The trial began on 2021-07-07, and primary completion was 2022-02-17. The study’s stated duration was 8 weeks.

Eligible participants were Chinese adults with type 2 diabetes who were receiving metformin as background antihyperglycemic medication. The registry lists PF-06882961 and placebo as the interventions. The PF-06882961 arm description says participants would be titrated up to 6 weeks of the 8-week dosing duration to reach the desired dose level of 120 mg. Further details of titration, dose changes, adherence, or eligibility criteria are not reported in the registry record.

The listed design uses parallel groups, but the primary outcome presents results for PF-06882961 at 40 mg BID, 80 mg BID, and 120 mg BID, with measurements on different days. It reports 15 participants for each of the 40 mg BID and 80 mg BID results and 14 for the 120 mg BID result. Those counts describe the outcome entries; they do not establish how participants moved between dose levels or whether every participant contributed to more than one entry. That information is not reported in the registry record.

Placebo appears as a study intervention, and the safety record includes placebo and pooled PF-06882961 BID groups. The primary outcome is not a placebo-controlled efficacy contrast: it summarizes PF-06882961 exposure. The registry lists four secondary outcome descriptions involving vital signs, electrocardiograms, treatment-emergent treatment-related adverse events, and laboratory abnormalities. Their numerical results are not reported in the registry record.

The record does not report the randomization procedure, allocation ratio, concealment details, sample-size justification, interim analyses, or a full statistical analysis plan. The design label alone does not answer those questions. The registry states that the planned analysis for the primary endpoint was not considered reliable by the sponsor, a qualification that matters when interpreting the posted values.

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.

BLINDED TREATMENT

Follow-Up

Analysis population for the primary outcome, as defined in the registry: All participants randomized and treated with PF-06882961 who had at least 1 plasma concentration value collected.

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 enrolled participants who were randomized and received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as AUC24 of PF-06882961 in Participants Received 40 mg BID, 80 mg BID, and 120 mg BID PF-06882961, measured over Pre-dose, 1, 2, 4, 6, 8, 10, 12, 14, 24 hours post dose on Day 21 (40 mg BID), 35 (80 mg BID), and 56 (120 mg BID).

The primary endpoint is AUC24 of PF-06882961, measured in ng*hr/mL. AUC24 represents the area under the concentration-time curve across a 24-hour interval and is used in pharmacokinetics to summarize drug exposure over that interval. Concentration measurements contribute to the curve, so AUC24 condenses a series of observations into one exposure measure rather than describing a single blood concentration.

The registry specifies pre-dose and post-dose measurement times of 1, 2, 4, 6, 8, 10, 12, 14, and 24 hours. Measurements are linked to Day 21 for 40 mg BID, Day 35 for 80 mg BID, and Day 56 for 120 mg BID. The reported summary parameter is the geometric mean, with geometric coefficient of variation as the dispersion statistic.

Geometric summaries are commonly used for pharmacokinetic measures because exposure values can be skewed and can vary multiplicatively. The geometric mean describes a central value on a multiplicative scale; the geometric coefficient of variation describes relative variability around that summary. These are general statistical interpretations, not evidence that the distributional assumptions were checked in this study.

The endpoint can characterize measured drug exposure in the participants included in each dose-level result. It does not, by itself, establish a clinical benefit, compare clinical outcomes with placebo, or show how exposure relates to response. The registry says the planned analysis was not considered reliable by the sponsor. The reason and any replacement analysis are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does AUC24 summarize?

As a general pharmacokinetic concept, AUC is the area under a concentration-time curve. It combines concentration information across time, giving a summary of overall exposure during the specified interval. AUC24 refers to a 24-hour interval in this study. It differs from a concentration at one time point: a single concentration reflects one sample, whereas AUC24 is intended to represent the course of exposure over the interval.

The registry lists pre-dose and post-dose collection times of 1, 2, 4, 6, 8, 10, 12, 14, and 24 hours. AUC estimation depends on the observed concentration data and the method used to construct the curve. The detailed computational method, handling of values below quantification limits, and rules for incomplete sampling are not reported in the registry record.

Why report a geometric mean?

As a general statistical explanation, pharmacokinetic measurements can have a right-skewed distribution: a limited number of high values may sit far above the central part of the data. A geometric mean is calculated on a multiplicative scale and is often used for such measures. It provides a central summary that is less directly influenced by extreme values than an arithmetic mean would be, though it does not remove the influence of unusual observations or guarantee a suitable model.

The geometric coefficient of variation is a measure of relative spread around a geometric summary. Large values signal considerable variability on the scale used for the measure. Here the posted coefficients are 236.0, 1414.0, and 2327.0 for the three listed dose-level results. The registry does not provide confidence intervals for the geometric means, participant-level values, or a detailed definition of how the coefficients were calculated. The displayed summaries therefore do not reveal the full shape of the exposure distributions.

What do the dose-level entries permit?

The record associates the 40 mg BID result with Day 21, the 80 mg BID result with Day 35, and the 120 mg BID result with Day 56. This is important because the entries vary in both dose and measurement day. A direct comparison of their summary values would mix dose-level and timing differences unless the statistical design and analysis account for them. The record does not describe whether participants contributed to multiple dose-level results, how repeated observations were modeled, or whether comparisons across doses were prespecified.

The record labels the study as parallel, but does not give enough detail to explain how that label relates to the three PF-06882961 dose-level outcome entries. The counts attached to those entries are 15, 15, and 14. They should not be added to infer a number of distinct participants, because participants may or may not overlap across entries. The participant-level relationship is not reported in the registry record.

What does the sponsor’s reliability statement mean?

The registry says that the planned analysis was not considered reliable by the sponsor. This is an important qualification because it signals that the posted endpoint should not automatically be interpreted as the result of a fully trusted prespecified analysis. The reason for that judgment, any analysis changes, and any sponsor-preferred results are not reported in the registry record. The posted geometric summaries remain descriptive information, but the stated concern restricts confidence in using them for formal inference.

No p-values, confidence intervals, or other inferential analyses are posted for this primary endpoint. A confidence interval, as a general concept, gives a range of values compatible with a statistical procedure and the observed data, subject to its assumptions. Without one, readers cannot assess the reported precision by that means. The absence of a posted interval does not itself establish that an effect is absent; it means the registry record does not provide that particular uncertainty summary.

How should the planning illustrations be understood?

As a general statistical concept, sample-size planning asks how many participants may be needed under specified assumptions to detect a target effect at a chosen significance level and power. Such calculations rely on assumptions about the effect size, variability, allocation, and analysis method. They do not describe the observed evidence from the completed trial.

The registry’s planning illustration uses the observed effect as its basis, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers target effects expressed as fractions of the observed effect. For non-time-to-event outcomes, the convention is participants per arm for the stated power; time-to-event illustrations use a total number of events. These are hypothetical planning quantities, not observed power and not evidence that the trial was designed with those sample sizes. The registry does not report the trial’s own sample-size justification.

Because the primary endpoint is described as an other endpoint rather than a two-arm comparison, the record does not support treating a two-arm sample-size illustration as a direct design reconstruction for this pharmacokinetic analysis. Any planning value should be interpreted only under its stated assumptions, not as a claim about the trial’s actual design or precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four secondary outcome descriptions: clinically significant change from baseline in vital signs, abnormal electrocardiogram, treatment-emergent treatment-related adverse events, and laboratory abnormalities. It also reports eight outcome measures in total, but numerical results for those secondary outcomes are not reported in the registry record. The registry lists zero analyses. It therefore does not provide a basis for describing secondary-outcome estimates, their uncertainty, or their statistical significance.

Multiplicity arises when multiple outcomes, time points, or comparisons are tested. As a general statistical matter, conducting many tests can increase the chance of observing at least one apparently unusual result by chance. Common approaches include prespecifying a primary test, adjusting significance thresholds, or treating secondary findings as exploratory. The multiplicity strategy for this study is not reported in the registry record. The existence of several listed outcome measures does not show whether or how the study addressed multiplicity.

The primary outcome population is described as randomized and treated participants receiving PF-06882961 who had at least one plasma concentration value collected. This definition indicates that the posted pharmacokinetic endpoint does not necessarily include every enrolled participant. The registry does not report the number excluded from the endpoint population, reasons for any unavailable measurements, or methods for handling missing concentrations.

Randomization is listed as a design feature, but the record does not specify an intention-to-treat analysis population, a per-protocol population, or rules for deviations and withdrawals. It also does not report whether missingness was considered related to dose, exposure, or participant characteristics. Without such information, the likely direction or impact of missing data cannot be determined.

There are no posted confidence intervals or p-values for the primary endpoint, and no inferential analysis is listed. These omissions prevent assessment of uncertainty using conventional inferential summaries. They should not be filled by assumptions about the analysis plan or by interpreting the registry’s planning illustrations as observed evidence.

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 safety record separates serious adverse events from other adverse events and deaths. In the placebo group, 5 participants were at risk for each category; no serious adverse events and no deaths were reported, while 5 participants had other adverse events. In the PF-06882961 BID group, 15 participants were at risk; no serious adverse events and no deaths were reported, while 14 participants had other adverse events.

These are counts of participants with events, not counts of the total number of events. The record does not list serious adverse event terms, and it does not provide event-level descriptions or timing. Although the listed secondary outcomes include treatment-emergent treatment-related adverse events, the registry’s group counts do not establish that every “other” event was treatment-related. The relationship of these counts to the secondary outcome definition is not reported in the registry record.

As a general statistical point, zero observed serious events in a study does not prove that the underlying risk is zero. Small safety groups provide limited information about uncommon events, and a comparison between groups is especially uncertain when the groups are limited in size. The counts are descriptive observations within this study, not a definitive test of comparative safety. They should be read alongside the study’s Phase 1 setting and limited enrollment, without extrapolating beyond the participants and observation period described in the registry.

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

The results establish that the registry contains geometric mean AUC24 summaries for PF-06882961 at three dose levels and reports adverse-event counts for placebo and pooled PF-06882961 BID groups. They describe observations collected in a randomized, double-blind, sponsor-open, placebo-controlled Phase 1 study of Chinese adults with type 2 diabetes receiving metformin. The endpoint’s measurements occurred on different days across the listed dose levels.

They do not establish a clinical effect on diabetes. AUC24 is a measure of drug exposure, not a clinical outcome, and the registry does not post efficacy comparisons against placebo. It does not support a claim that one dose is superior to another, because dose and measurement day vary together, the participant relationship across entries is unclear, and the sponsor considered the planned analysis unreliable. No p-values or confidence intervals are posted for the primary endpoint.

The values also do not establish the likely exposure of every participant. The geometric means summarize groups, while the geometric coefficients of variation indicate substantial relative spread, particularly in the 80 mg BID and 120 mg BID entries. The registry does not provide participant-level concentrations or other distributional summaries that would show how individual observations relate to the group summaries.

On safety, the posted counts show no serious adverse events or deaths in either of the two reported groups during the study observation period. They also show other adverse events in 5 of 5 placebo participants and 14 of 15 PF-06882961 BID participants. These observations do not demonstrate that serious events cannot occur or establish a comparative safety profile. The record’s limited enrollment and lack of event details constrain interpretation.

The trial is therefore most informative as a small Phase 1 registry record of pharmacokinetic summaries and descriptive safety counts. It does not answer questions about long-term outcomes, broader populations, or comparative clinical benefit. Such questions are not reported in the registry record, and no conclusions on them should be inferred from these exposure summaries.

13. Why This Trial Matters Statistically

This study illustrates a distinction central to clinical biostatistics: a reported endpoint can be quantitatively precise in format while still having limited inferential support. The registry gives geometric means, geometric coefficients of variation, dose levels, and measurement days, but does not provide confidence intervals or p-values. The sponsor’s statement that the planned analysis was not considered reliable further cautions against treating the summaries as definitive comparisons.

It also illustrates why endpoint timing and design context matter. The AUC24 entries are attached to different doses and different measurement days. Statistical interpretation depends on understanding whether observations are independent or repeated, how dose changes were handled, and what analysis was planned. Those details are not reported in the registry record. Without them, a reader should not turn a pattern among summaries into a causal dose-response conclusion.

The high geometric coefficients of variation highlight the importance of variability in pharmacokinetic data. As a general matter, group averages can conceal broad individual differences, and estimates can be difficult to interpret when uncertainty is not quantified. The record makes the variability visible but does not provide enough detail to assess its sources or the precision of the central estimates.

The safety results offer a related lesson: absence of observed serious adverse events in a small study is not equivalent to evidence that serious events are impossible. Event counts are useful descriptive information, but they do not resolve uncommon risks or provide a robust comparison between groups. The registry reports no serious event terms and does not provide detailed event-level results.

Finally, the record distinguishes study planning from observed results. Sample-size illustrations based on an observed effect are hypothetical exercises under stated assumptions, not a reconstruction of the trial’s actual design and not observed power. This distinction helps prevent planning calculations from being mistaken for evidence about what the completed study demonstrated.

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 primary outcome has an explicit reliability caveat: the sponsor did not consider the planned analysis reliable. The record does not explain why, identify a replacement analysis, or report sponsor conclusions about the posted results. This is a central limitation for any inferential interpretation of the AUC24 summaries.

The registry provides no confidence intervals or p-values for the primary outcome and lists zero analyses. It also does not report a detailed statistical analysis plan, sample-size justification, multiplicity strategy, or interim analyses. These omissions mean readers cannot verify how the analysis addressed uncertainty, repeated observations, or multiple outcome measures.

The three dose-level summaries correspond to different measurement days: Day 21, Day 35, and Day 56. The record does not clarify how participants contributed across entries or whether dose and time effects were considered together. The outcome counts of 15, 15, and 14 cannot be interpreted as distinct groups or summed to derive a participant total. The reason for variation in outcome counts is not reported in the registry record.

Dispersion is large for the 80 mg BID and 120 mg BID summaries, while participant-level observations and confidence intervals are unavailable. The registry also does not report the AUC estimation procedure or how incomplete concentration profiles were handled. Consequently, the precision and robustness of these exposure summaries cannot be independently assessed from the record.

Safety reporting is limited to group counts for serious events, other adverse events, and deaths. Serious event terms and further event-level detail are not reported in the registry record. With enrollment of 20 and safety groups at risk of 5 and 15, the study offers limited evidence about uncommon events. The secondary outcomes are listed, but their results are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of PF-06882961 in Chinese Adults With Type 2 Diabetes Mellitus — NCT04889157.
• Registry record last updated 2024-10-01; status last verified 2024-06.
• Results first posted 2024-10-01.
• 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

NCT04889157 is a completed, randomized, double-blind, sponsor-open, placebo-controlled Phase 1 study of PF-06882961 in Chinese adults with type 2 diabetes receiving metformin. The registry reports 20 participants enrolled and an 8-week study. It lists PF-06882961 and placebo as interventions.

The primary endpoint is AUC24 of PF-06882961, measured in ng*hr/mL. The record posts geometric mean values of 1446.0 for 40 mg BID, 1012.0 for 80 mg BID, and 984.9 for 120 mg BID, with geometric coefficients of variation of 236.0, 1414.0, and 2327.0, respectively. The measurements are associated with Day 21, Day 35, and Day 56, respectively. The sponsor did not consider the planned analysis reliable.

Safety counts include no serious adverse events or deaths in either reported group. Other adverse events affected 5 of 5 placebo participants and 14 of 15 PF-06882961 BID participants. Four secondary outcomes are listed, but their numerical results are not reported in the registry record. The posted information is descriptive and does not provide a placebo comparison for the primary pharmacokinetic endpoint.