Multiple Dose Study Of PF-05231023 In Obese Adult Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multiple Dose Study Of PF-05231023 In Obese Adult Subjects (NCT01923389), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

The trial’s stated purpose was to assess safety, tolerability, pharmacokinetics and pharmacodynamics after multiple doses of PF-05231023 in obese adult subjects. The posted primary outcome focuses on adverse events, while listed secondary outcomes include laboratory measurements and measures describing drug concentrations and disposition. These outcomes address different questions: event counts describe reported medical occurrences, whereas pharmacokinetic measures characterize concentrations over time.

The registry record lists 4 participants enrolled, with 2.0 in the placebo arm and 2.0 in the PF-05231023 100 mg arm. These small group counts make the posted outcome a descriptive account of this trial, rather than a precise estimate of how frequently events might occur in a wider population. No broader population inference is established by the record.

3. Trial Design

The registry record identifies this as a Phase 1, randomized, placebo-controlled trial with a parallel-group model and quadruple masking. The official title describes multiple intravenous doses of PF-05231023 in obese adult subjects. The listed interventions are placebo and 100 mg PF-05231023. The record does not explain which trial roles were included in the masking designation, how randomization was carried out, or the schedule and duration of dosing.

The trial enrolled 4 participants. The posted arm counts are 2.0 for placebo and 2.0 for PF-05231023 100 mg. The record lists Type 2 Diabetes Mellitus (T2DM) as a condition, but does not report how many participants had that condition or provide baseline demographic or clinical characteristics. It is therefore not possible to describe the enrolled group in greater detail from this record.

The record lists the start as 2013-09 and primary completion as 2013-12, and gives the status as terminated. The reason for termination and the timing or circumstances of that decision are not reported in the registry record. The listed follow-up period for the primary adverse-event outcome runs from Day -7 through the last follow-up (Day 68).

Safety, tolerability, pharmacokinetics and pharmacodynamics are named as study objectives. The primary outcome is the number of participants with adverse events. Listed secondary outcomes cover abnormal clinical laboratory measurements and several pharmacokinetic measures, including concentration over a dosing interval, peak and lowest observed concentrations, average concentration at steady state, time to peak concentration, clearance and terminal elimination half-life. The registry record does not give detailed methods for measuring these outcomes.

The record does not report the planned allocation ratio, a sample-size justification, the reason for selecting the dose, or a detailed protocol. Although the arm counts are the same in the posted results, the randomization procedure and intended allocation 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).

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 participants who received at least 1 dose of study medication (PF-05231023 or placebo).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over Day -7 through the last follow-up (Day 68).

The primary endpoint is the number of participants with adverse events. The registry record defines an adverse event as any untoward medical occurrence in a participant who received study drug, without regard to the possibility that the event was caused by the study drug. This definition describes how events are classified; it does not establish that a treatment caused an event.

The stated timeframe is Day -7 through the last follow-up (Day 68). The record also notes that adverse events were reported for the 7-day pre-randomization period. Including an observation period around treatment helps characterize events reported during the trial, but the record does not explain how events arising before randomization were distinguished from those arising later in analysis.

Counting participants with at least one event is a clinically interpretable safety summary: it indicates how many people in each arm had an event recorded, rather than how many separate events each person experienced. This kind of endpoint can support a descriptive account of safety experience in a trial. It does not, by itself, identify event severity, duration, recurrence, or causal relationship for every event.

The primary outcome is listed for all participants who received at least 1 dose of study medication, either PF-05231023 or placebo. The posted results give a value of 2.0 in each arm, with an arm size of 2.0 in each. The record does not provide a confidence interval or an inferential comparison for this endpoint. Given the limited group counts, the endpoint should be read as a description of the enrolled participants, not as a precise estimate of event frequency beyond this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Understanding the posted outcome starts with its scale. The primary endpoint is a count of participants who experienced an adverse event. For this kind of binary participant-level outcome, each participant is classified according to whether an event was recorded during the stated period. The result is reported as a number of participants, rather than as a continuous measurement such as a concentration or a time-to-event value.

What does the posted count describe?

In this trial, the registry record gives a primary outcome value of 2.0 for placebo and 2.0 for PF-05231023 100 mg. The arm sizes are 2.0 in both groups. These values describe the recorded participants in the trial. They are not a model-based estimate, and the record does not report a statistical test or an uncertainty interval for the comparison.

In general, event-count comparisons can be described using a difference in proportions, a relative measure, or a model for binary outcomes. These approaches answer related but distinct questions and require choices about the estimand, analysis population, and statistical assumptions. No such treatment contrast is reported in the registry record. No new contrast should be substituted for the sponsor’s analysis, and no sponsor comparison is available in the record.

Why is precision important?

In general, estimates based on small groups tend to be imprecise: a change in the event status of a participant can substantially change the observed group summary. Confidence intervals are one way to communicate that uncertainty. They do not guarantee that an estimate contains the true value, but they show the range of values compatible with the data under a chosen method. No confidence interval is reported for the primary endpoint, so the precision of a treatment comparison is not quantified.

The equal observed counts do not answer whether an underlying difference exists. In general, a failure to identify a difference is not the same as evidence of equivalence. Equivalence requires an explicitly defined margin and an analysis designed to evaluate it. The registry record does not report an equivalence objective or analysis. It would therefore be inappropriate to describe these results as demonstrating equivalence.

What can randomization and masking contribute?

In general, random assignment aims to make treatment groups comparable with respect to measured and unmeasured characteristics, on average, while masking can reduce the influence of treatment knowledge on care or outcome assessment. The registry record labels the study randomized and quadruple-masked, but does not specify the randomization method or who was masked. The labels describe design features; they do not indicate how well those features were implemented, and they do not remove uncertainty from the small group counts.

The record identifies a parallel design, meaning the listed arms are separate treatment groups rather than a crossover sequence. The record does not provide further design details such as allocation procedures, dose schedule, or rules for handling missed doses. Those details matter when interpreting the conduct and analysis of a trial, but should not be reconstructed from the design label.

How should the analysis population be understood?

The primary population is described as all participants who received at least 1 dose of study medication. This is a treatment-received definition. The registry record does not report whether an intention-to-treat population, a per-protocol population, or another analysis set was also defined. It also does not give participant-level data or explain how participants with incomplete follow-up were handled.

In general, analysis populations are defined before analysis to clarify who contributes to each estimate. Different populations can answer different questions. For example, including all randomized participants can preserve the comparison created by randomization, whereas restricting analysis to those who received treatment addresses a different population. No additional population definition or sensitivity analysis is reported in the registry record.

What do the pharmacokinetic outcomes measure?

The listed secondary outcomes include AUCtau, Cmax, Cmin, Cav, Tmax, clearance and terminal elimination half-life for specified components of PF-05231023. In general, AUC describes exposure across a defined interval; Cmax and Cmin describe peak and lowest concentrations observed in that interval; Cav describes an average concentration at steady state; Tmax is the time to peak concentration; clearance characterizes removal from the body; and half-life characterizes the time course of terminal elimination. These concepts help distinguish exposure and disposition measures from event-count outcomes.

The record also lists abnormal clinical laboratory measurements. Laboratory outcomes and pharmacokinetic measurements are not interchangeable with the primary adverse-event count. Each requires its own definition, time window, and analytic summary. Numerical results and detailed analysis methods for these secondary measures are not reported in the registry record details.

What analyses are missing?

The registry record lists 0 analyses and indicates that a two-arm comparison is not estimable for the binary endpoint because values are missing or not estimable for that comparison. No p-value, confidence interval, adjusted analysis, or effect estimate is reported. The record does not report a statistical analysis plan, a sample-size justification, interim analyses, or specific methods for multiplicity or missing data.

In general, sparse event data can challenge standard approximations used in statistical tests and interval estimates. Exact methods or carefully chosen models may be considered depending on the question and design, but the record does not identify an analysis method. It is therefore not possible to assess whether a particular method was planned or used. The posted arm counts should be interpreted as descriptive results, without attaching an unreported inferential conclusion.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo", "PF-05231023 100 mg")
n      <- c(2, 2)
events <- c(2, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  PF-05231023 100 mg  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary adverse-event outcome and secondary outcomes covering clinical laboratory measurements and pharmacokinetic measures. It does not report a statistical analysis plan describing how these outcomes were prioritized or how multiplicity was handled. In general, testing multiple outcomes can increase the chance of a false-positive finding if each is assessed separately without an appropriate strategy. Whether that issue affected this trial cannot be assessed from the record.

The record lists 13 outcome measures and 9 posted secondary outcomes. It does not provide numerical results for the secondary outcomes in the registry record reported for this analysis. Those outcomes therefore cannot be used to corroborate, qualify, or contrast with the primary safety counts. The record also lists 0 analyses, and no inferential comparison for the primary endpoint is available.

Missing-data methods are not reported in the registry record. The primary analysis population is described as participants who received at least 1 dose, but the record does not say whether all such participants completed follow-up, how missing event information was handled, or whether any sensitivity analyses were conducted. The posted values should not be taken as evidence that there were no missing observations unless the record explicitly reports that.

In general, missingness can affect interpretation when the likelihood of having an observed outcome is related to treatment or participant characteristics. A complete-case summary, an imputation procedure, and a sensitivity analysis may have different implications. No such procedures are described, so their use or impact cannot be determined.

The registry record does not report interim analyses, stopping rules, or a sample-size justification. Although the trial status is terminated, the reason for termination and any relationship to the analysis are not reported. No assumptions about multiplicity, missing data, or stopping decisions should be inferred from the status or from the posted counts alone.

12. 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 serious adverse event figures are 0 of 2 participants in the placebo arm and 0 of 2 participants in the PF-05231023 100 mg arm. These are the posted serious-event counts for the trial. They describe what was recorded among participants in each arm; they do not establish that the risk of a serious event is zero in a wider population.

The registry record also reports other adverse events in 2 of 2 participants in each arm. These figures concern the category of other adverse events and should not be conflated with the serious-event counts. The primary endpoint reports participants with adverse events overall, while the separate safety summary distinguishes serious events from other events.

In general, a zero count in a small group is compatible with substantial uncertainty about the underlying event frequency. A confidence interval could communicate that uncertainty, but none is reported for these serious-event figures. The registry record does not report deaths as a numerical result, so the absence of a listed death count should not be interpreted as a reported zero.

The adverse-event definition does not require a causal relationship to study drug. Accordingly, these counts are not counts of events established to have been caused by PF-05231023 or placebo. The record does not report serious adverse event terms, event-level descriptions, severity detail, or attribution judgments.

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

The posted results describe a small randomized trial of PF-05231023 100 mg compared with placebo. For the primary outcome, the registry record reports 2.0 participants with adverse events in each arm, with an arm size of 2.0 in each. The separate safety summary reports no serious adverse events in either arm and other adverse events in both arms. These are observations in the trial, not definitive estimates of how often events would occur in a broader population.

The results do not establish that PF-05231023 causes, prevents, or has no effect on adverse events. The adverse-event definition explicitly does not depend on whether an event was considered causally related to study medication. The record does not report an inferential comparison, an uncertainty interval, or a causal attribution analysis. Equal observed counts cannot establish that underlying risks are equal.

The registry record’s study objectives include safety, tolerability, pharmacokinetics and pharmacodynamics, but the registry entries reported for this analysis do not include numerical results for the listed pharmacokinetic or laboratory outcomes. The primary endpoint alone cannot answer questions about drug concentrations, exposure, clearance, or pharmacodynamic response.

The outcome period spans Day -7 through the last follow-up (Day 68), with events also reported during the 7-day pre-randomization period. That timeframe is important context for reading the counts. It does not by itself clarify which events occurred before or after treatment, how events were adjudicated, or whether follow-up was complete; those details are not reported in the registry record.

The record identifies the trial as Phase 1, randomized, quadruple-masked and parallel, and states that it was terminated. It does not explain why it was terminated or provide enough detail to evaluate the consequences for recruitment, follow-up, or analysis. The results are therefore best understood as a limited descriptive record of the trial’s posted safety experience, with important uncertainty and missing methodological detail.

14. Why This Trial Matters Statistically

This trial illustrates why event counts from early-phase studies need careful interpretation. The registry record describes a Phase 1 study focused on safety, tolerability, pharmacokinetics and pharmacodynamics. Its primary endpoint counts participants with adverse events, making the result easy to describe but also highly dependent on the small number of participants represented in each arm.

The observed counts are the same in the placebo and PF-05231023 100 mg arms. That equality is informative as a description of these posted results, but it is not a substitute for an estimate of precision or a formal comparison. The registry record does not report a confidence interval or an inferential analysis. Readers should distinguish an observed equality from evidence that treatment groups have equal underlying risks.

It also matters that the endpoint is defined without regard to a possible causal relationship. This is useful for collecting untoward medical occurrences broadly, but it means the count is not a direct measure of treatment-caused harm. The separate serious-event figures add another descriptive safety dimension, while still not resolving causal attribution or uncertainty.

More broadly, the record shows the limits of interpreting trial summaries when analysis details are sparse. Randomization and quadruple masking are reported, but procedures and analysis populations beyond the treatment-received primary population are not described. The record also does not explain the terminated status. Such omissions do not invalidate the reported counts, but they constrain the conclusions that can reasonably be drawn from them.

The study’s listed pharmacokinetic and laboratory outcomes point to different scientific questions from the primary adverse-event count. Keeping those outcome types distinct is important: a safety count cannot stand in for concentration or disposition results, and those results are not numerically reported in the record details.

15. 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 main limitation for interpretation is the limited number of participants represented in each arm: the record lists 2.0 for placebo and 2.0 for PF-05231023 100 mg. Counts from groups of this size offer little precision for estimating event frequency beyond the trial. The record does not provide confidence intervals or another uncertainty measure for the primary or serious adverse-event counts.

The trial status is terminated, but the reason is not reported in the registry record. Without that information, it is not possible to determine whether termination affected recruitment, treatment exposure, outcome collection, or the planned analysis. The record does not report whether the stated enrollment was the planned target or whether recruitment ended as intended.

Participant characteristics are not described beyond the trial’s focus on obese adult subjects and the condition listing for Type 2 Diabetes Mellitus (T2DM). No baseline information is reported in the registry record, so the composition of the enrolled group and the applicability of results to other populations cannot be assessed in detail.

Important design and analysis details are also absent. The randomization method, masking roles, dose schedule, sample-size justification, statistical plan, missing-data procedures, interim analyses, and multiplicity strategy are not reported in the registry record. The primary population is defined as participants who received at least 1 dose, but the record does not describe other analysis sets or follow-up completeness.

The adverse-event endpoint counts participants with events and does not itself describe event-level details, severity beyond the separate serious-event classification, duration, recurrence, or causal attribution. Numerical results for the listed secondary laboratory and pharmacokinetic outcomes are not reported in the registry record. These limitations restrict both the safety interpretation and any assessment of the broader study objectives.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multiple Dose Study Of PF-05231023 In Obese Adult Subjects — NCT01923389.
• Registry record last updated 2014-09-17; status last verified 2014-09.
• Results first posted 2014-09-17.
• 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.

19. Record Summary

The registry record describes NCT01923389, “Multiple Dose Study Of PF-05231023 In Obese Adult Subjects,” as a Phase 1 randomized, placebo-controlled, quadruple-masked, parallel trial. The official title describes multiple intravenous doses. The listed arms are placebo and PF-05231023 100 mg, with 2.0 participants in each arm and 4 enrolled overall.

The primary outcome is the number of participants with adverse events during Day -7 through the last follow-up (Day 68). The posted outcome value is 2.0 in each arm. The separate serious adverse event summary reports 0 of 2 participants in each arm, while other adverse events are reported in 2 of 2 participants in each arm.

The record lists pharmacokinetic and laboratory secondary outcomes, but numerical results for those measures are not reported in the registry record. It reports 0 analyses and no estimable binary two-arm comparison. The trial is listed as terminated; the reason is not reported in the registry record.