A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus (NCT01044537), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs).

2. Clinical Question

The study’s stated purpose was to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics after single escalating oral doses. The primary endpoint addresses safety by identifying participants who experienced an event during the treatment-emergent observation period. It is a count of affected participants, rather than a measure of how many total events occurred or how severe each event was.

The registry also identifies secondary outcomes involving responses to a mixed meal tolerance test on Day 1. These include measures based on glucose, insulin, and C-peptide, such as changes in post-prandial area-under-the-curve measures and ratios of hormone responses to glucose responses. The listed outcomes indicate what biological measures were of interest; they do not, by themselves, establish the direction or size of any observed effect. Results for those measures are not reported in the registry record.

Accordingly, the central statistical question that can be addressed from the posted counts is descriptive: how many participants in each listed group were recorded as having serious or other adverse events? The record does not provide a reported inferential test or a single combined estimate answering whether event frequency differed across doses and placebo.

3. Trial Design

The registry describes a randomized, triple-masked, parallel Phase 1 trial. The study was completed, with enrollment listed as 50. The recorded study start was 2010-02 and primary completion was 2010-05. These registry descriptors establish the broad design and timing, but do not provide a full account of how the trial was conducted.

The intervention was PF-04937319, administered as single oral doses across ascending-dose cohorts. The registry lists six dose levels: 10 mg, 30 mg, 100 mg, 300 mg, 480 mg, and 640 mg. Placebo was used as a comparator. The arm descriptions state that each ascending-dose cohort would include approximately 6 participants receiving active treatment and 3 receiving placebo, and describe approximately 6 dosing levels. The posted results list a placebo group of 16 participants, while active-treatment group sizes are 6 for several doses and 5 for two doses.

Randomization means that treatment assignment is intended to be determined by chance, which can reduce systematic differences between groups. Masking is intended to limit the influence of treatment knowledge on care or assessment; the registry labels the trial triple-masked but does not specify which roles were masked or how masking was maintained. A parallel design assigns participants to a group rather than having each participant receive multiple treatments in sequence; the details of assignment and implementation are not reported in the registry record.

The trial was designed around single-dose exposure and early safety, pharmacokinetic, and pharmacodynamic characterization. That purpose differs from a study intended to estimate long-term clinical outcomes. The registry record does not report the rationale for the selected dose levels, the sequence and decision rules for dose escalation, or a sample-size justification. It also does not describe whether dose escalation depended on interim safety review. Those details should not be inferred from the fact that the doses are listed in ascending order.

The registry lists 15 outcome measures, including the primary safety endpoint and secondary metabolic measures. It reports 0 analyses. Thus, the design record provides useful context for the observed group counts, but does not supply a complete statistical analysis plan or a set of comparative results.

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.

Only the first 6 of 7 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who received at least 1 dose of study medication.

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: Safety analysis set included all participants who received at least 1 dose of study medication.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs), measured over Day 1 up to 10 days after last dose of study medication (up to 11 days).

The primary endpoint is the number of participants with treatment-emergent AEs or SAEs. The registry defines an AE as any untoward medical occurrence in a participant who received study medication, without requiring that the event be considered caused by the medication. An SAE is an event resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, a congenital anomaly, or an event otherwise judged significant.

For this endpoint, treatment-emergent events are those occurring between the first dose and up to 10 days after the last dose, if they were absent before treatment or worsened relative to the pretreatment state. The stated timeframe is Day 1 up to 10 days after the last dose of study medication, described as up to 11 days. This defines the observation window; it does not describe longer-term safety after that period.

Counting affected participants is useful for a basic safety description because it indicates how many people experienced at least one event. It is different from counting every event: one participant can experience more than one event, while the participant count still represents that person once for the endpoint. The registry’s posted figures separate serious events from other events, which helps distinguish these categories without implying that all events have the same clinical importance.

The endpoint is descriptive as presented in the record. A participant count alone does not establish causality, quantify event severity beyond the serious/non-serious distinction, or provide a precise comparative effect. The registry record does not report a single primary-endpoint comparison or an inferential analysis across the treatment groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, triple-masked, and parallel. These terms describe different aspects of the design. Randomization concerns assignment to treatment; masking concerns who knows the assignment; and a parallel design means participants are followed in their assigned groups rather than crossing through multiple treatments. These design features can help limit bias, but their labels alone do not show how well they were implemented. Further operational details are not reported in the registry record.

What does a participant count represent?

For the primary safety endpoint, the unit is participants. A count such as 4 of 6 means that 4 participants in that listed group were recorded as affected by the specified category, among 6 at risk. This is not the same as saying that 4 events occurred: one person may have more than one event. The registry reports participant counts for SAEs and other AEs separately. It does not report event-level descriptions for the listed non-serious events.

A group count is a descriptive statistic. It conveys the observed frequency in the participants recorded for that group, but it does not by itself estimate how much the outcome would differ under another treatment for a broader population. Such an estimate would ordinarily need a defined comparison, an analysis method, and a measure of uncertainty. A comparative estimate and its uncertainty are not reported in the registry record.

Why does uncertainty matter?

General statistical explanation: a confidence interval expresses the range of values reasonably compatible with the data under a specified method and assumptions. It makes precision visible, rather than presenting an estimate as if it were exact. With small groups and uncommon outcomes, the range of plausible underlying event frequencies can be wide even when the observed count is zero. The registry record does not report confidence intervals for these safety counts.

A p-value, in general, measures how compatible observed data are with a specified null model, assuming that model and the analysis assumptions are appropriate. It is not the probability that a treatment is effective or safe, and it does not measure the size or importance of an effect. No p-value or formal test for the primary endpoint is reported in the registry record. In the absence of such a test and a stated comparison, the descriptive counts should not be converted into a claim of statistical significance or lack of significance.

How should dose groups be read?

The active groups correspond to distinct single-dose levels. They are not repeated observations from the same individuals, based on the parallel-design description. The listed active-group denominators are 6 for 10 mg, 30 mg, 100 mg, and 300 mg, and 5 for 480 mg and 640 mg. The placebo group denominator is 16. Group sizes are small, so single participants account for a meaningful portion of the observed group counts. No dose-response model or trend test is reported.

General statistical explanation: over-dispersion matters when observed variation is greater than a chosen statistical model expects. In count or event data, ignoring extra variation can make uncertainty appear too small. The registry does not identify a model for the safety endpoint, report an over-dispersion assessment, or provide enough analyses to determine whether this issue was evaluated. No particular model should be attributed to the trial based solely on the outcome type.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These assumptions define hypothetical planning calculations; they are not evidence that the trial was designed using those calculations or that its observed data had a particular power.

Such illustrations depend on the assumed effect size, analysis method, significance level, allocation, and other design choices. They are not observed power, and they do not establish the adequacy of the original sample size. The sample-size justification for this study is not reported in the registry record. The record also says that time-to-event illustrations give total events using the Schoenfeld approach, while other illustrations give participants per arm. These are planning conventions, not observed trial outcomes.

What cannot be inferred from the posted analyses?

The registry reports 0 analyses. This means the record does not provide inferential analysis details for the listed outcomes. It does not specify adjustment variables, statistical models, handling of repeated measurements, or rules for choosing among dose comparisons. Nor does it provide a primary endpoint estimate with a confidence interval. General statistical methods can explain what such procedures would do, but they cannot fill in methods that are not reported.

The mixed meal tolerance test outcomes involve changes from baseline, percent changes, ratios, and area-under-the-curve measures. These outcome definitions indicate the types of quantities planned for assessment; they do not specify the exact statistical model, missing-data handling, or multiplicity procedure. Their numerical results and inferential analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary safety outcome and secondary outcomes related to glucose, insulin, and C-peptide responses after a mixed meal tolerance test. Several secondary measures use related biological quantities, including area-under-the-curve measures, ratios, and changes from baseline. When many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. General statistical practice may address this with a prespecified hierarchy, adjustment, or a clearly exploratory interpretation.

A multiplicity strategy for this trial is not reported in the registry record. The record does not state whether one outcome was designated as the sole confirmatory test, whether secondary outcomes were exploratory, or whether any adjustment for multiple outcomes or dose comparisons was planned. The registry reports 0 analyses, so it does not provide a set of inferential results from which an adjustment strategy can be identified. No claim about adjusted or unadjusted significance can be made.

Missing-data methods are also not reported in the registry record. The safety analysis set included all participants who received at least 1 dose of study medication, but that definition does not state how missing safety information would be handled. It also does not describe the analysis populations used for pharmacokinetic or pharmacodynamic outcomes, or how incomplete measurements in the mixed meal tolerance test would be addressed.

The record does not report the number of participants with missing outcome measurements, reasons for missingness, imputation procedures, or sensitivity analyses. These omissions matter because missingness can affect which participants contribute to an outcome and may affect the interpretation of estimates. The available group counts can be described as posted, but they do not resolve how missing data were managed for other endpoints.

In the absence of reported multiplicity and missing-data procedures, the metabolic outcomes should not be interpreted as confirmatory findings, and no unreported analysis plan should be assumed. The trial’s safety counts remain descriptive observations for the groups and follow-up period identified in the registry.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 participants with SAEs in each PF-04937319 dose group and 0 in the placebo group. For other AEs, the recorded counts are 1 of 6 at 10 mg, 4 of 6 at 30 mg, 1 of 6 at 100 mg, 3 of 6 at 300 mg, 3 of 5 at 480 mg, 3 of 5 at 640 mg, and 0 of 16 for placebo. The counts describe participants affected, not the total number of events.

Zero observed SAEs does not demonstrate that the risk is zero. These groups are small, and the observation period runs from Day 1 up to 10 days after the last dose, described as up to 11 days. The counts therefore apply to the participants and period recorded, not to longer use or other populations.

The registry defines AEs without requiring a causal link to study medication. The posted counts cannot establish that PF-04937319 caused an event, and the record does not provide event-level details for the other AEs. It also does not report a formal comparison, confidence intervals, or p-values. Read the figures as descriptive safety observations, not as proof of equivalence between groups or a definitive ranking of doses.

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

The registry record supports a limited, concrete description of early safety observations after single doses. No SAEs are recorded among the participants listed in any dose group or the placebo group. Other AEs are recorded in some active-dose groups and not in the placebo group, with the participant counts varying across dose levels. These figures describe what was observed in the listed groups during the stated treatment-emergent period.

They do not establish whether PF-04937319 caused any particular event. The AE definition includes untoward occurrences regardless of a possible causal relationship, and the record does not identify the types or clinical courses of the other AEs. The counts also do not show how an individual participant’s risk compares under active treatment versus placebo with statistical precision. No primary-endpoint comparison, confidence interval, or inferential test is reported.

The zero SAE counts should not be read as evidence that serious events are impossible. The groups are small and exposure was a single dose, with safety follow-up extending up to 10 days after the last dose. The findings do not describe safety with repeated or longer-term dosing, and they cannot automatically be generalized beyond the enrolled adults with Type 2 Diabetes Mellitus.

The study had broader stated aims, including pharmacokinetic and pharmacodynamic characterization. The registry lists mixed meal tolerance test outcomes involving glucose, insulin, and C-peptide, but numerical results for these measures are not reported in the registry record. Consequently, the posted safety counts do not answer whether those biological measures changed or how precisely any such changes were estimated.

Overall, the record conveys observed participant counts in a small, early-phase study. It does not establish a treatment benefit, a definitive safety profile, a dose-response relationship, or the absence of risk. Those conclusions would require results and analyses not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its design and posted data illustrate the difference between an early-phase safety description and a comparative treatment-effect analysis. The registry records randomization, masking, a placebo comparator, and escalating single-dose cohorts. Those design elements provide structure for examining safety, but they do not compensate for the lack of reported inferential analyses.

Small group counts are especially important when interpreting uncommon events. A zero count is an observation, not proof that the underlying event frequency is zero. Likewise, differences between small groups may be unstable. Confidence intervals and a defined comparison would help communicate uncertainty, but neither is reported for the primary endpoint. The record therefore encourages careful separation of the observed counts from broader conclusions.

The study also demonstrates why the endpoint definition matters. The primary measure counts participants with treatment-emergent AEs or SAEs, whereas event-level totals, severity details beyond the SAE distinction, and causal attribution are different questions. Separating serious events from other events gives one useful view, but it does not substitute for a complete account of event types and outcomes.

Finally, the registry lists multiple metabolic outcomes alongside the safety objective. Related outcomes can require a clear analysis hierarchy and transparent multiplicity handling. The record does not report such a strategy or the outcome analyses. This makes the distinction between planned measures and available evidence essential: an outcome’s presence in a registry entry is not itself a result.

The statistical lesson is not to overstate what a compact set of counts can establish. Clear descriptions of denominators, observation windows, analysis populations, and uncertainty are central to responsible interpretation, particularly in small dose-escalation studies.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific details unavailable. The sample-size justification, eligibility criteria beyond the population description, and the rationale for selecting the dose levels are not reported in the registry record. The operational procedure for escalation, including any decision rules or interim safety reviews, is also not reported. Those details cannot be reconstructed from the ascending dose list.

The posted safety data are limited to participant counts for serious and other AEs by listed group. The record does not report event names for the non-serious events, event-level totals, severity gradations beyond the SAE category, timing within the follow-up period, or outcomes such as resolution. It also does not report whether any observed event was judged related to study medication.

The primary endpoint combines AEs and SAEs, but the registry does not provide a single combined primary-endpoint result or a reported comparison across groups. The separate counts cannot be combined into an unambiguous participant-level result without information about overlap. No confidence intervals, p-values, or formal dose-trend analyses are reported.

Although the registry lists 15 outcome measures, it reports 0 analyses. Results for the listed pharmacokinetic and pharmacodynamic outcomes are not reported in the registry record. Statistical models, multiplicity procedures, missing-data methods, and analysis populations for those outcomes are likewise not reported. The safety analysis set is defined, but that definition does not resolve how other outcome data were handled.

Finally, the study concerns single escalating doses and a short treatment-emergent observation window. Its findings cannot establish long-term safety or outcomes under repeated exposure. These limitations define the reach of the record rather than invalidate the descriptive counts that are posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus — NCT01044537.
• Registry record last updated 2017-03-10; status last verified 2017-01.
• Results first posted 2017-03-10.
• 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 trial enrolled 50 adults with Type 2 Diabetes Mellitus and evaluated single escalating oral doses of PF-04937319 against placebo. The registry describes the study as randomized, triple-masked, and parallel, with six listed dose groups and a placebo group. The primary endpoint counted participants with treatment-emergent AEs or SAEs during the stated period extending up to 10 days after the last dose.

No SAEs are listed in any group. Other AE counts vary across the active-dose groups, while the placebo group lists 0 of 16 participants with other AEs. These are descriptive participant counts and do not establish causality or a comparative treatment effect. The registry does not report a single primary-endpoint comparison, inferential analyses, or results for the listed metabolic outcomes. Sample-size justification, multiplicity handling, and missing-data methods are not reported in the registry record.