A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066 (NCT01250730), a registered phase 1 study. The primary outcome is Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib.

2. Clinical Question

This is a pharmacokinetic study question rather than a comparison of clinical benefit. The endpoint is intended to summarise drug exposure over time after dosing. The record describes concentration sampling through 144 hours post-dose and gives the calculation used to extrapolate the area under the curve. It does not report the resulting endpoint values by dose group, uncertainty around those values, or an estimated relationship between dose and exposure.

The design can describe observations in the three dose cohorts, but the registry record does not establish a randomized, like-for-like comparison. It does not report allocation procedures, and there is no separate control arm in the listed cohort description. Consequently, a difference between cohorts, if reported elsewhere, would need to be interpreted with attention to how participants entered each cohort and to the limited group sizes. Here, the posted record does not include numerical pharmacokinetic results with which to make that comparison.

3. Trial Design

The registry describes a Phase 1, open-label, dose-escalation, single oral dose study in Japanese healthy male volunteers. The study is marked as completed. Its stated purpose is to investigate the pharmacokinetics of PF-02341066 at 150 mg, 250 mg, and 400 mg in the fasted condition. The listed study model is parallel, and masking is recorded as none.

The cohort description assigns 6 participants to each of the three dose groups. The total enrollment is 18. The record describes the groups as PF-02341066 treatment groups, while the primary endpoint is labelled as an endpoint for crizotinib. The record does not explain this difference in naming, so it should not be resolved by assumption. It also does not provide additional details about participant characteristics, eligibility criteria, dose sequence, or the timing of each cohort’s dosing.

The registry lists a study start of 2010-12 and a primary completion of 2011-01. These dates describe the record’s study timeline; they do not supply details about the conduct of individual visits or sampling procedures beyond the endpoint timeframe. The listed sampling times extend from 0 through 144 hours post-dose.

This is not a randomized comparison according to the registry information. The allocation method is not stated, and the listed arms are not a like-for-like control comparison. The dose groups therefore should be read as cohorts in a dose-escalation study, not as randomized treatment and control groups. The record does not say whether escalation decisions were prespecified, what criteria governed them, or whether any dose was withheld or changed.

The registry lists 17 outcome measures and no analyses. It supplies the primary endpoint’s definition and timeframe, but not numerical endpoint estimates. The statistical analysis plan, sample-size justification, interim analyses, and analysis populations are not reported in the registry record. The posted information thus supports a description of the design and available adverse-event counts, but not a quantitative assessment of the primary pharmacokinetic outcome.

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: Twelve healthy subjects were assigned to open-label crizotinib treatment in either the 150 mg cohort (6 subjects) or 250 mg cohort (6 subjects). After the completion of assessment of safety at both 150 mg and 250 mg cohorts, the 400 mg cohort, the highest dose level in this study, was started.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib, measured over 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose.

The primary endpoint is the area under the plasma concentration-time profile from time zero extrapolated to infinite time, described as AUC(0-inf) of crizotinib and measured in ng*hr/mL. In general, an area under a concentration-time curve summarises drug exposure across the observed period and the extrapolated portion beyond the last measurable sample. It is used in pharmacokinetic studies because a single concentration at one time may not represent the overall exposure after a dose.

The registry describes the endpoint as estimated from crizotinib concentration. It defines AUC(0-inf) as AUClast plus (Clast/kel): AUClast is the area under the plasma concentration-time curve from zero until the last measurable concentration; Clast is the last quantifiable concentration; and kel is the terminal phase elimination rate constant. The listed concentration sampling timeframe runs from 0 to 144 hours post-dose.

The endpoint is labelled as a geometric mean with standard deviation as its dispersion measure. In general, a geometric mean can summarise values that are treated on a multiplicative scale, while a dispersion statistic conveys variability. The registry record does not explain the analysis scale, the calculation of the reported dispersion, or whether any transformation was used.

Most importantly, the posted results do not give numerical AUC(0-inf) values, group-level estimates, or uncertainty intervals. The endpoint definition explains what the study intended to measure, but it cannot show the observed exposure or how precisely that exposure was estimated in any cohort.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described are limited to the endpoint definition and the information about summaries included in the registry record. The record does not report the analysis procedures used to produce the primary endpoint results, and it lists no analyses. The discussion below separates the stated endpoint construction from general statistical context; it does not attribute unreported methods to the study.

What does the primary endpoint summarise?

AUC(0-inf) is an exposure summary: it represents the area under a concentration-time curve, starting at time zero and extending to infinite time through an extrapolation. The record describes measurements at 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hours post-dose. In general, concentration measurements over time describe the observed part of the curve. AUC(0-inf) also depends on an estimate of the remaining area after the last quantifiable concentration.

The registry gives the construction as AUC(0-inf) = AUClast + (Clast/kel). AUClast is the area from zero time until the last measurable concentration. Clast is the final quantifiable concentration, and kel is the terminal phase elimination rate constant. The record explains these terms but does not report participant-level concentration data or the resulting AUC values. It also does not specify the computational procedures used to estimate the curve or terminal phase rate constant.

What does the summary label tell us?

The primary endpoint is identified as a geometric mean, with standard deviation listed for dispersion. In general, a geometric mean describes a central value on a multiplicative scale and is often used when measurements have a skewed distribution. A standard deviation describes spread around a summary, but its interpretation depends on the scale on which it is calculated. The registry record does not state whether the standard deviation is on the original or transformed scale, or give further details about the summary method.

Those labels alone do not reveal the result. Since the record contains no numerical endpoint estimate, readers cannot inspect its spread or compare the groups’ exposure summaries. A confidence interval would convey uncertainty around an estimated quantity, but no such interval for the primary outcome is reported in the registry record. General statistical interpretation of precision therefore cannot be applied to the primary endpoint.

What does the cohort structure allow?

The study is described as parallel and open label, with three dose cohorts. In general, a parallel design observes different participants in separate groups, while masking concerns whether treatment assignment is concealed from participants or study personnel. The registry lists masking as none. It does not state how participants were assigned to cohorts. The record’s own description says this is not a randomized comparison and that the arms are not a like-for-like control comparison.

As a general principle, comparisons between groups are most straightforward when the design supports comparable groups and the analysis accounts for the design. Here, the record does not describe randomization, a control group, or an adjusted comparison. It would therefore be inappropriate to interpret any difference between the cohorts as an isolated causal effect of dose on the basis of this record. In this case, the record does not provide numerical AUC results in the first place.

What cannot be inferred about the analysis?

The registry record does not report the statistical analysis plan, sample-size justification, interim analyses, or analysis populations. It does not specify how missing concentrations were handled, how values below quantification were treated, or how the terminal phase was selected. It also does not state whether endpoint estimates were calculated per participant before group summaries, or describe any checks of assumptions. These are not details that can be reconstructed from the endpoint definition.

The record lists 17 outcome measures but no analyses. That distinction matters: an outcome measure describes what is to be assessed, whereas an analysis ordinarily describes how observed data are summarised or compared. The endpoint definition and sampling timeframe are not substitutes for reported statistical methods or numerical estimates.

How should the event counts be read?

The safety information is presented as counts of participants at risk and counts with events. In general, counts are descriptive and do not by themselves quantify uncertainty or establish a difference between groups. The registry lists 6 participants at risk in each cohort and reports other adverse-event counts for each dose group. These small cohort counts should not be converted into a claim of comparative risk. The record does not provide event-level detail here, statistical comparisons, or uncertainty estimates for these counts.

Any sample-size illustrations displayed elsewhere on the page should be read as planning illustrations based on an observed effect, not as observed power and not as the study’s original design justification. The registry record does not report the trial’s own sample-size rationale. Such illustrations cannot fill in the missing primary endpoint results or make the posted cohorts a randomized comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures but does not list analyses. It names a primary endpoint, yet does not report numerical results for it. The record does not explain how the primary endpoint was prioritized in the analysis, whether additional endpoints were considered confirmatory or exploratory, or how multiple statistical tests, if any, were handled. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

In general, multiplicity matters when several hypotheses are tested: repeated testing can increase the chance of finding an apparently notable result by chance. Whether and how that concern applies depends on the questions and analyses actually planned. Since the analysis plan and results are not reported, no claim can be made about the use or adequacy of multiplicity control. The count of outcome measures alone does not establish how many tests were performed.

The record also does not report missing-data procedures or analysis populations. It gives no account of missing concentration samples, participants excluded from particular analyses, or rules for handling incomplete pharmacokinetic profiles. The primary endpoint description depends on the last measurable concentration and an extrapolated terminal component, but the record does not specify what was done when either could not be estimated.

The analysis population is not identified in the posted information. The record does not say whether all enrolled participants, all dosed participants, or another defined group contributed to endpoint summaries. It also does not describe any interim analyses or stopping rules. These omissions mean that readers cannot establish from the registry record how the outcome-measure list was translated into analyses or how missing information affected the reported findings. No numerical primary result is posted to evaluate in any case.

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 reports serious adverse-event counts of 0 in each dose group, with 6 participants at risk in each group. These are the serious-event figures recorded for the cohorts; they do not establish that no serious events could occur in a larger or different population. The record does not report deaths in the information.

For other adverse events, the registry reports 2 participants in the 150 mg group, 0 in the 250 mg group, and 1 in the 400 mg group. These should be read as cohort-level descriptive counts, not as evidence that one dose is safer than another. The groups are small, allocation is not stated, and the study is not a randomized like-for-like comparison.

The event terms, timing, duration, severity, and relationship to treatment are not reported in the registry record. The counts therefore cannot distinguish different types of events or provide a fuller account of their clinical context. Nor should the absence of a reported serious event be interpreted as proof of no risk. The figures describe only what is posted for this study record.

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

This study record is useful for identifying the intended question and basic design: a Phase 1, open-label study of single oral doses of PF-02341066 in fasted Japanese healthy male volunteers, organised into three dose cohorts. It names a pharmacokinetic endpoint, describes its construction, and records adverse-event counts. Those elements help readers understand what the study set out to measure and what safety information is posted.

The record does not, however, provide numerical results for the primary AUC(0-inf) endpoint. It therefore does not show the observed exposure at any dose, the variability in exposure, or the precision of the estimates. It cannot support a conclusion from the registry record about a dose-response pattern. This is not evidence for or against any particular pattern; the relevant values are not reported in the registry record.

Likewise, the listed adverse-event counts are descriptive and arise from small cohorts without a separate control group or reported random allocation. They do not establish comparative safety across doses. The available record does not include event-level detail sufficient to interpret types or circumstances of the reported events, and deaths are not reported in the registry record.

The study is not a clinical efficacy trial in the information posted. Its stated objective concerns pharmacokinetics, and the record does not provide clinical benefit outcomes or an efficacy comparison. Any inference beyond the descriptive design and posted event counts would require information not contained in this registry record.

In short, the record describes what was planned and gives a limited account of adverse events, but leaves the central numerical pharmacokinetic result unavailable. That distinction is important: endpoint definitions and study design explain the intended analysis question, while only reported estimates and their uncertainty can show what the data indicate and how precisely.

13. Why This Trial Matters Statistically

This study illustrates a basic distinction in clinical biostatistics: an endpoint can be precisely defined in a registry without its numerical result being available there. The record identifies AUC(0-inf), gives the concentration-based construction, and specifies a sampling timeframe. That is enough to understand the intended pharmacokinetic summary, but not enough to assess the observed exposure or its uncertainty.

It also shows why design labels matter when interpreting comparisons. The study is described as open label, parallel, and dose escalating, with three cohorts. The record does not state allocation procedures and explicitly does not describe a randomized, like-for-like control comparison. Those details constrain what a between-cohort contrast could mean, even if numerical results were present. In this record, no primary endpoint values are posted.

The adverse-event information is another useful example of the difference between descriptive counts and comparative evidence. The registry reports counts by cohort, but the group sizes are limited and event details are absent. The figures can be read as recorded observations, not as a formal comparison of risks or proof of safety.

Finally, the record lists multiple outcome measures but no analyses. Statistical interpretation depends not only on what is measured, but also on how the analysis was planned, which participants were included, how missing observations were handled, and how multiple outcomes were considered. These details are not reported. Recognising the boundary between what a registry entry documents and what it leaves unknown is essential to a careful reading of trial evidence.

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 central limitation for interpretation is that the registry record does not report numerical results for the primary pharmacokinetic endpoint. Although AUC(0-inf) is defined and its sampling timeframe is given, there are no group estimates, dispersion values, or uncertainty intervals to assess. The endpoint name also refers to crizotinib while the study and intervention descriptions refer to PF-02341066; the registry record does not explain that naming difference.

The cohort description gives 6 participants per dose group, but the record does not report participant-level characteristics or the method used to allocate participants to cohorts. It is marked as open label, and no separate control group is described. The registry explicitly notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison. This constrains comparative interpretation.

The posted safety information is limited to counts. Event terms and details about timing, severity, duration, or relationship to treatment are not reported in the registry record. Deaths are not reported in the registry record. The counts cannot provide a complete characterization of safety or support a reliable comparison between dose cohorts.

The registry does not report the statistical analysis plan, sample-size justification, interim analyses, analysis populations, missing-data procedures, or multiplicity approach. It lists 17 outcome measures and no analyses. These omissions limit assessment of how results were to be analysed and how completely they are represented. The record’s study dates and completion status do not supply those missing methodological details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066 — NCT01250730.
• Registry record last updated 2011-11-29; status last verified 2011-10.
• Results first posted 2011-11-29.
• 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 describes a completed Phase 1, open-label, parallel, single oral dose study in Japanese healthy male volunteers. Its stated purpose is to investigate PF-02341066 pharmacokinetics in the fasted condition. The cohort description lists 150 mg, 250 mg, and 400 mg groups, with 6 participants in each; total enrollment is 18.

The primary endpoint is AUC(0-inf) of crizotinib, measured in ng*hr/mL, with a geometric mean and standard deviation listed. The registry describes the endpoint calculation and concentration sampling through 144 hours post-dose, but does not report numerical primary endpoint results. It lists 17 outcome measures and no analyses.

The record reports no serious adverse events in the listed groups and other adverse-event counts of 2, 0, and 1 participants across the respective dose groups. Event details and deaths are not reported in the registry record. Allocation procedures, analysis methods, missing-data handling, and sample-size justification are also not reported.