Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes (NCT01396187), a randomized phase 1 study. The primary outcome is Number of Participants With Abnormal Physical Examination Findings.

2. Clinical Question

The study was designed to assess safety and tolerability alongside pharmacokinetics and pharmacodynamics of multiple ascending doses. The listed secondary outcomes concern PF-05231023 concentrations and exposure after a single dose and at steady state, including maximum observed concentration, time to maximum concentration, and measures of exposure. An accumulation ratio is also listed.

The registry does not report a single comparative estimate for the primary outcome or a statistical test comparing PF-05231023 with placebo. It therefore does not establish from the posted primary-outcome information whether the frequency of abnormal findings differed between groups. The available adverse-event counts describe participants in each group, but they are not a substitute for a prespecified comparative analysis.

3. Trial Design

This was a Phase 1 randomized, placebo-controlled trial with a parallel-group model and triple masking. The registry records 50 participants enrolled and lists adults with type 2 diabetes mellitus as the study population. Pfizer is the sponsor. The listed intervention groups are placebo and PF-05231023 at 5 mg, 25 mg, 100 mg, and 140 mg. The registry title describes ascending intravenous doses, but the arm descriptions themselves are blank.

The recorded study start is 2011-07 and the primary completion date is 2012-05. The study status is completed. The primary outcome timeframe is baseline up to Day 42. The registry does not report further details of the dose schedule, the duration between doses, or the timing of measurements within that timeframe.

Randomization means that allocation to trial groups is intended to be determined by chance, which can help limit systematic differences at the start of a study. The registry does not report the randomization method, allocation ratio, or any stratification factors. Triple masking indicates that masking was used, but the registry record does not specify which roles were masked or how masking was maintained.

The stated objectives include safety, tolerability, pharmacokinetics, and pharmacodynamics. The listed secondary outcomes are pharmacokinetic measures of exposure and concentration after single dosing and at steady state. The registry does not provide a specific pharmacodynamic outcome in the listed secondary outcomes. It also does not report detailed eligibility criteria, the analysis population, or the planned statistical model.

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: Dose of PF-05231023 was escalated based on sponsor's and investigator's discretion, depending upon safety, tolerability and pharmacokinetic profile of PF-05231023.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Physical examination data reported in this study was for identification of adverse events and were reported as adverse event in the AE section.

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 population included all participants who received at least 1 dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Abnormal Physical Examination Findings, measured over Baseline up to Day 42.

The primary outcome is the number of participants with abnormal physical-examination findings from baseline up to Day 42. The listed physical examination included assessment of height, weight, blood pressure, pulse rate, and body temperature. The registry says that the investigator used discretion to determine whether a finding was abnormal and that qualifying findings were reported as adverse events.

This kind of outcome is used to record physical findings that may be relevant to safety during a study. In general, recording the number of participants with at least one qualifying finding gives a participant-level summary, rather than a count of every measurement or repeated finding. However, the registry description does not give a detailed threshold or standardized rule for classifying an examination finding as abnormal; it specifies investigator discretion.

The registry also says that physical-examination data in this study were collected to identify adverse events and were reported in the adverse-event section. A numerical result for the primary outcome itself is not reported in the registry record. Consequently, the outcome definition can be described, but the posted record does not provide the number of participants meeting this primary endpoint or a comparison between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group trial with placebo control and triple masking. Random allocation is generally intended to make group assignment independent of participant characteristics, reducing the risk that systematic selection determines who receives each intervention. Masking is generally intended to reduce the influence of knowledge about assignment on participant experience, clinical assessment, or outcome reporting. The registry does not report the randomization procedure, allocation ratio, masking roles, or methods used to preserve masking, so those design features cannot be evaluated in detail.

What does a participant count represent?

For an outcome expressed as the number of participants with a finding, each participant is counted according to whether they meet the outcome definition during the specified period. This differs from counting every occurrence: a person with repeated findings may still contribute only once to a participant-level count. In this trial, the primary outcome is described as participants with abnormal physical-examination findings from baseline up to Day 42. The registry says the investigator determined abnormality at discretion and that findings were reported as adverse events. It does not report the primary-outcome counts by group.

How should group counts be compared?

In general, a comparison of two groups can be expressed as a difference in event proportions, a relative measure, or a model-based estimate. An estimate conveys the direction and magnitude of the observed contrast; a confidence interval describes the range of values compatible with the data and the chosen statistical assumptions. A p-value, when reported, addresses how compatible the observed data are with a specified null model. None of these inferential summaries for the primary outcome or adverse-event groups is reported in the registry record.

Counts from small groups can be imprecise: a change in the status of one participant can noticeably change the observed group proportion. In general, confidence intervals are especially useful for showing that uncertainty rather than relying on a binary interpretation of statistical significance. No confidence intervals are reported for these adverse-event counts, and no new intervals should be inferred from the record alone.

What is the role of the pharmacokinetic outcomes?

The listed secondary outcomes include area under the concentration-time curve, maximum observed plasma concentration, and time to maximum observed concentration. In general, area under the curve summarizes drug exposure over a specified interval, maximum observed concentration records the highest measured concentration, and time to maximum concentration describes when that peak was observed. The registry lists these measures after a single dose and, for several measures, at steady state. It also lists an accumulation ratio for area under the curve. These outcome definitions identify the kinds of measurements planned or recorded, but they do not reveal the numerical results. Numerical pharmacokinetic findings are not reported in the registry record.

The trial title and official title describe multiple ascending intravenous doses and assessment of pharmacokinetics and pharmacodynamics. In general, ascending-dose designs can examine outcomes across dose groups, but the registry record does not report the dose-escalation rules, decision criteria, or statistical model. The blank arm descriptions also leave dosing schedules and group-specific procedures unspecified. No conclusion about the pattern of pharmacokinetic response across doses can be drawn without the corresponding results.

What do planning calculations mean?

In general, sample-size planning estimates how many participants may be needed to detect a specified effect under stated assumptions. The planning illustration described for this trial uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it defines the effect to detect as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed power and not evidence that the trial had that power. The registry does not report its own sample-size justification or the assumptions used to set enrollment. A planning illustration based on an observed effect cannot replace a prespecified design calculation.

Over-dispersion is a general concern when outcome variability exceeds what a simple statistical model assumes. It can make standard errors too small if the model does not allow for the extra variability, leading to overly narrow confidence intervals or misleading tests. The primary outcome is a participant count, and the registry does not identify an analysis model or provide the data needed to assess model fit or over-dispersion. Therefore, no claim about whether over-dispersion affected the trial analysis is supported.

Finally, the registry lists zero analyses. This means that no inferential analysis is recorded in the registry record describing the results. It does not establish which methods might have been used in a separate report; those methods are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary pharmacokinetic outcomes. Testing several outcomes can raise a multiplicity issue: in general, the more statistical tests performed, the greater the chance of at least one apparently unusual result under a collection of null hypotheses. A statistical plan may address this by specifying a hierarchy of outcomes or an adjustment procedure. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or any inferential analyses.

The record does not report how missing measurements or withdrawals were handled, whether all randomized participants were included in each analysis, or how analysis populations were defined. These details matter because exclusions and missing observations can affect which participants contribute to an estimate and can potentially change the results. The enrollment is recorded as 50, but that fact alone does not establish the number analyzed for any outcome.

The registry also does not report a statistical analysis plan, a protocol-defined estimand, or an explanation of how protocol deviations were handled. These items are not reported in the registry record. Without them, the posted information does not support an assessment of whether the outcome analyses followed a prespecified strategy or how missingness and multiple outcomes were addressed.

Because no primary-outcome analysis or inferential results are recorded, it is not possible to assess statistical significance, precision, or robustness for that endpoint from this record. Descriptive adverse-event counts remain useful as recorded observations, but should not be mistaken for a complete analysis of all planned outcomes.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: femoral neck fracture (10.0%).

The registry lists serious adverse events by group as affected participants out of participants at risk: placebo, 0 of 8; PF-05231023 5 mg, 0 of 12; PF-05231023 25 mg, 0 of 10; PF-05231023 100 mg, 0 of 10; and PF-05231023 140 mg, 1 of 10. These are observed counts within the listed groups. The registry does not report a statistical comparison of serious-event risk between groups.

The leading serious adverse-event term is listed as femoral neck fracture at 10.0%. The record does not identify the group associated with this term listing, so it cannot be assigned to a particular dose group from the information recorded. Death counts are not reported in the registry record.

Other adverse-event counts are presented separately from serious events. The registry lists 5 of 8 affected participants for placebo, 6 of 12 for PF-05231023 5 mg, 3 of 10 for PF-05231023 25 mg, 8 of 10 for PF-05231023 100 mg, and 10 of 10 for PF-05231023 140 mg. These counts do not show how many distinct event types each person experienced or establish whether an event was caused by the intervention. Group sizes are limited, and no uncertainty intervals or adjusted comparisons are reported.

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

The record establishes that a randomized, placebo-controlled Phase 1 trial assessed multiple ascending intravenous doses of PF-05231023 in adults with type 2 diabetes. It identifies a primary safety outcome based on abnormal physical-examination findings up to Day 42 and lists pharmacokinetic outcomes related to concentration and exposure. It also records serious and other adverse-event counts for placebo and four dose groups.

Those details do not provide a numerical result for the primary endpoint, a comparative treatment estimate, or inferential analyses. The adverse-event counts are descriptive and cannot determine whether differences between groups are beyond what might occur by chance. They also do not establish that a recorded event was caused by PF-05231023. The registry does not give enough detail to interpret the serious adverse-event term by treatment group, and death counts are not reported in the registry record.

In general, a trial result should be interpreted in light of its design, outcome definitions, analysis population, uncertainty, and missing data. Several of those elements are not reported in the registry record. The listed secondary outcomes indicate that pharmacokinetic measurements were part of the study, but numerical results for those outcomes are not reported in the record. No claim about pharmacokinetic or pharmacodynamic effects can be supported from outcome titles alone.

The record therefore documents the study’s design and selected safety observations, rather than a complete statistical answer to its stated questions. The absence of a reported analysis is not evidence that an outcome had no difference or that no events occurred. It means that the relevant estimate and its precision cannot be evaluated from this registry information.

13. Why This Trial Matters Statistically

This trial illustrates a distinction that matters in biostatistics: a registry can specify outcomes and design features while providing limited numerical analysis of those outcomes. The primary endpoint is described in detail enough to identify its timeframe and the examinations involved, but the record does not give the participant count meeting that endpoint by group. Without those results, the primary question cannot be answered quantitatively from the registry record.

The study also shows why event counts should be read alongside group sizes and uncertainty. The serious adverse-event counts include one affected participant in the PF-05231023 140 mg group and zero in the other listed groups. Those observations are informative descriptions, but the record has no comparative estimate or confidence interval to convey their precision. A count alone should not be read as proof of a dose-related pattern.

The multiple dose groups and pharmacokinetic objectives make the study relevant for thinking about how outcomes are organized in an early-phase randomized trial. The registry lists exposure and concentration measures at different dosing stages, but does not provide their numerical results or the analysis plan. Thus, this record is a useful example of how an outcome inventory is different from a reported statistical result.

For clinical researchers, the practical statistical lesson is to distinguish what was measured, what was observed, and what was estimated. The record identifies the first and gives selected descriptive observations, but it does not provide enough inferential detail to evaluate treatment contrasts or their precision.

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 contains blank arm descriptions, so the dose schedules and other group-specific procedures are not described. It names randomized allocation and triple masking but does not report how randomization was performed, who was masked, or how masking was maintained. Eligibility criteria and the analysis population are also not reported in the registry record.

The primary outcome relies on investigator discretion to classify examination findings as abnormal. The record lists the examination measures but does not provide quantitative classification thresholds or group-specific primary-outcome counts. It states that physical-examination findings were reported as adverse events, but does not give enough detail to connect the primary endpoint to a separately reported numerical result.

Safety reporting is limited to affected-participant counts and a listed serious-event term. The registry does not report event-level timing, duration, severity details for the other-event counts, or a treatment-group assignment for the femoral neck fracture term. Death counts are not reported in the registry record. No comparative estimates, confidence intervals, or p-values are recorded.

The registry lists pharmacokinetic outcomes but does not include their numerical results in the record. It also does not report a statistical analysis plan, multiplicity handling, missing-data methods, sample-size justification, or the number analyzed for each outcome. These omissions prevent a fuller assessment of precision, analysis choices, and the potential influence of missing observations. The findings that can be described are therefore limited to the design details and posted adverse-event counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability of Ascending Intravenous Doses of PF-05231023 In Adult Subjects With Type 2 Diabetes — NCT01396187.
• Registry record last updated 2015-01-12; status last verified 2014-12.
• Results first posted 2015-01-12.
• 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

The registry identifies NCT01396187 as a completed Phase 1 randomized, placebo-controlled, triple-masked, parallel-group trial sponsored by Pfizer. It records enrollment of 50 adults with type 2 diabetes, a study start of 2011-07, and primary completion in 2012-05. The trial title describes multiple ascending intravenous doses of PF-05231023.

The primary outcome was the number of participants with abnormal physical-examination findings from baseline up to Day 42. The registry explains that findings were judged at investigator discretion and reported as adverse events, but a numerical result for this primary outcome is not reported in the registry record. The listed secondary outcomes concern pharmacokinetic exposure and concentration.

Serious and other adverse-event counts are recorded by placebo and dose group, but comparative analyses and uncertainty estimates are not reported. The record lists zero analyses. It does not report a sample-size justification, detailed statistical plan, missing-data methods, or analysis populations.