A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of PF-04958242 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of PF-04958242 in Healthy Subjects (NCT02341482), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval, Where Tau = 12 Hours (AUCtau) of PF-04958242.

2. Clinical Question

The trial’s stated purpose was to characterize the pharmacokinetic profile of PF-04958242 when co-administered with a strong CYP3A4 inhibitor. Itraconazole was the named inhibitor in the study title and treatment description. The primary endpoint was AUCtau, the area under the concentration-time profile from time 0 to the end of the dosing interval, with tau defined as 12 hours.

This question concerns drug concentration over time, rather than a clinical benefit or health outcome. The registry record describes repeated pharmacokinetic assessments across the study days and identifies the endpoint’s two relevant conditions: PF-04958242 0.025 mg alone and PF-04958242 0.025 mg combined with itraconazole 200 mg. Because participants followed a fixed sequence and there was no random allocation or masking, the comparison should be read as a within-study sequence of assessments, not as a randomized, blinded treatment contrast.

The record lists healthy participants and does not describe a patient population with a condition being treated. The trial therefore addresses a pharmacokinetic question in healthy adults. It does not, from the information reported, establish how any concentration change would relate to clinical outcomes or to people outside the studied population.

3. Trial Design

This was a Phase 1, open-label, non-randomized, single-group, fixed-sequence study sponsored by Biogen. The registry lists 13 participants enrolled. The study status is completed. Its stated purpose was to characterize PF-04958242 pharmacokinetics when co-administered with a strong CYP3A4 inhibitor; itraconazole was the named co-administered drug.

The endpoint description identifies an assessment of PF-04958242 0.025 mg on Day 3 and an assessment of PF-04958242 0.025 mg combined with itraconazole 200 mg on Day 17. These assessment days are part of a sequence, rather than parallel randomized arms. The record describes the study as fixed-sequence, and lists allocation as non-randomized and masking as none. Consequently, the design does not provide a randomized, blinded control comparison. Period, sequence, or other changes over time cannot be separated from the treatment condition on the basis of a randomized contrast in this record.

The arm description begins to give dosing details for PF-04958242 and itraconazole, but its text is incomplete in the registry record. The complete itraconazole schedule and the remainder of the dosing description are not reported in the registry record. The primary endpoint timeframe lists sampling on several days, with specified post-dose times on some days, and identifies Day 3 and Day 17 for the endpoint conditions of interest.

The registry lists 13 outcome measures and zero analysis entries. The record describes the pharmacokinetic analysis population as all participants enrolled and treated who had at least 1 of the pharmacokinetic parameters of interest measured. It does not report a randomized allocation ratio, masking procedures, a statistical analysis plan, a sample-size justification, or the numerical primary endpoint results. Those details should not be inferred from the design label or enrollment count.

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: The PK analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of interest measured.

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 Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval, Where Tau = 12 Hours (AUCtau) of PF-04958242, measured over Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21.

The primary endpoint is the area under the concentration-time profile from time 0 to time tau, where tau is the dosing interval and tau equals 12 hours. The record names this measure AUCtau for PF-04958242 and gives its unit as picogram*hours per milliliter pg*h/mL. AUC captures drug concentration across the interval, rather than describing concentration at just one sampling moment. It is used in pharmacokinetic assessment because it represents overall exposure during the defined interval.

The registry identifies the endpoint parameter as a geometric mean and its dispersion as a geometric coefficient of variation. It describes AUCtau collection at Day 3 for the PF-04958242 0.025 mg condition and Day 17 for the PF-04958242 0.025 mg plus itraconazole 200 mg condition. The listed timeframes include sampling at specified post-dose times on those days, along with additional assessment days.

In general, geometric summaries are used for measurements whose distributions may be asymmetric and where relative, rather than absolute, variation is of interest. A geometric coefficient of variation describes dispersion on a multiplicative scale; it is not the same quantity as a standard deviation. These are general interpretations of the statistical measures, not findings about the observed distribution in this trial.

The registry record does not report the actual AUCtau geometric means, geometric coefficients of variation, a between-condition estimate, or a confidence interval. Thus the endpoint’s definition and intended assessment are available, but the magnitude and precision of the observed pharmacokinetic contrast are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does AUCtau measure?

AUCtau is the area under the concentration-time profile across the dosing interval. In this study, the interval tau is 12 hours. Conceptually, the area reflects both the concentrations observed and how they change over time during that interval. It differs from a single concentration measurement, which refers to a specific sampling time. The registry lists AUCtau in picogram*hours per milliliter pg*h/mL and identifies the endpoint parameter as a geometric mean.

In general, pharmacokinetic measurements can be summarized to describe exposure and concentration patterns. That is a general explanation of the endpoint’s role; the registry record does not report the numerical AUCtau results for this study. It identifies Day 3 for PF-04958242 0.025 mg and Day 17 for PF-04958242 0.025 mg combined with itraconazole 200 mg as the endpoint assessment conditions.

Why report a geometric mean and geometric coefficient of variation?

In general, geometric summaries are useful when measurements are positive and are more naturally interpreted through relative changes or multiplicative variation. A geometric mean is based on a multiplicative scale, unlike an arithmetic mean, which adds measurements before averaging. The geometric coefficient of variation describes relative dispersion on that scale. It is not interchangeable with a standard deviation, and its interpretation depends on the scale used.

The registry names the geometric mean and geometric coefficient of variation as the endpoint summary and dispersion, but does not post their values. It also does not report whether the analysis transformed measurements, how any model was specified, or how uncertainty was calculated. The summary labels alone do not reveal the full statistical procedure.

How should the sequence affect interpretation?

In general, random allocation can help balance participant characteristics across treatment groups, while masking can reduce the influence of knowledge of treatment assignment on conduct or assessment. This study is listed as non-randomized, open-label, single-group, and fixed-sequence. The primary assessment conditions occurred at different points in that sequence: PF-04958242 0.025 mg on Day 3 and the same stated dose combined with itraconazole 200 mg on Day 17.

Because the conditions were not concurrent randomized groups, the comparison should not be interpreted as if participants had been randomly assigned to separate arms. The design labels do not establish that all other influences were controlled. The registry record does not report an analysis approach for sequence or time effects, nor does it provide a model specification. In general, a fixed sequence can make treatment condition and time in the study difficult to distinguish unless the design and analysis address that issue; whether or how it was addressed is not reported in the registry record.

What do confidence intervals and p-values ordinarily add?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater statistical precision, while a wider interval indicates less precision. A p-value describes how compatible the observed data are with a specified statistical null model, given the test assumptions; it does not measure the probability that a treatment effect is true. Neither quantity should be inferred from a point estimate alone.

The registry record reports no confidence interval, p-value, or estimated primary contrast. It therefore does not support an assessment of the primary result’s statistical precision or compatibility with a null hypothesis. No such result should be reconstructed from the enrollment count or endpoint description.

What does the analysis population mean?

The registry defines the pharmacokinetic analysis population as all participants enrolled and treated who had at least 1 of the pharmacokinetic parameters of interest measured. This definition describes eligibility for the population; it does not report how many participants met it, how many contributed AUCtau data, or whether all enrolled participants completed each assessment. The record lists 13 enrolled participants, but does not report endpoint-specific denominators or missingness.

In general, an analysis population definition matters because estimates depend on which participants and measurements are included. Missing measurements can affect both the amount of information and the representativeness of the analyzed group. The registry record does not describe missing-data handling, exclusions, or sensitivity analyses.

What can the safety counts establish?

The adverse-event entries provide participant counts at risk and affected for each listed treatment group. Serious adverse events are listed as affecting zero participants in each group. Other adverse events are listed as affecting 1 participant with PF-04958242 0.1 mg, 2 with PF-04958242 0.025 mg, and 7 with PF-04958242 0.025 mg combined with itraconazole 200 mg. These counts are descriptive, not inferential comparisons. The registry record does not give event-level details or an analysis of differences between groups.

In general, adverse-event counts do not by themselves establish whether an event was caused by treatment or how severe or clinically important it was. The serious-event term list is empty in the record, and death values are null. The interpretation of the null entries is not explained; deaths are not reported in the registry record.

Are planning calculations trial results?

In general, a sample-size calculation can illustrate the number of participants per arm needed for a chosen power and assumed effect under specified statistical assumptions. It is a planning exercise, not an observed treatment result or a measure of the power actually achieved. The registry record does not report the trial’s own sample-size justification or statistical plan. Any planning illustration based on an observed effect would not substitute for those missing design details, and no observed effect is reported for this primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary AUCtau endpoint and secondary pharmacokinetic and safety outcomes. The secondary outcomes include Tmax, Cmin, Ctrough, apparent oral clearance, and counts of participants meeting specified safety criteria. Listing multiple outcomes raises a general statistical issue: when several hypotheses are tested, the chance of at least one nominally significant finding can increase unless the analysis plan accounts for multiplicity. This is a general explanation, not a claim that such tests were performed in this study.

The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan specifying which outcomes were confirmatory. It lists zero analysis entries, and does not provide p-values or outcome estimates for the listed measures. Therefore, the record does not permit a review of how multiple outcomes or repeated assessment times were handled.

The endpoint population is defined as enrolled and treated participants with at least 1 pharmacokinetic parameter of interest measured. The number meeting that definition and the number contributing to each endpoint are not reported in the registry record. The record also does not report missing-data counts, reasons for missing measurements, imputation methods, or sensitivity analyses. In general, missing observations can reduce information and may affect interpretation if their occurrence relates to participant characteristics or outcomes; the pattern and handling of missingness in this study are not reported.

Enrollment was 13, but that count alone does not establish the primary endpoint denominator. Nor does it establish that every participant contributed every scheduled sample. The registry record does not report a sample-size justification, an interim-analysis plan, or stopping rules. Those design and analysis details should be treated as unreported rather than inferred from the trial’s Phase 1 designation or its enrollment.

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 for three treatment group entries. For PF-04958242 0.1 mg, 0 of 13 participants at risk were affected; for PF-04958242 0.025 mg, 0 of 13 were affected; and for PF-04958242 0.025 mg combined with itraconazole 200 mg, 0 of 13 were affected. The serious-event term list is empty. These entries indicate that the record lists no participants with serious adverse events in those groups; they do not provide event-level detail.

For other adverse events, the record lists 1 affected participant among 13 at risk with PF-04958242 0.1 mg, 2 among 13 with PF-04958242 0.025 mg, and 7 among 13 with PF-04958242 0.025 mg combined with itraconazole 200 mg. These are counts, not evidence of a statistically tested difference. The record does not specify the event terms, severity, timing, or whether an individual participant could contribute to more than one category.

The death fields are null. Their meaning is not explained in the registry record, so deaths are not reported in the registry record. In general, small descriptive safety counts do not establish comparative risk or causation. The non-randomized, fixed-sequence design also means these entries should not be read as results from randomized, concurrent control groups.

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

The record establishes that a completed Phase 1 study enrolled 13 healthy adult subjects and was designed to characterize PF-04958242 pharmacokinetics with itraconazole. It specifies AUCtau over a 12-hour dosing interval as the primary endpoint and identifies the assessment conditions on Day 3 and Day 17. It also describes the endpoint summary as a geometric mean with geometric coefficient of variation as dispersion. These registry entries explain the question and measurement, but do not provide the answer in numerical form.

The primary endpoint values and the estimated contrast between conditions are not reported in the registry record. Without those results, the size and direction of any observed change cannot be stated. The record also provides no confidence interval or p-value, so precision and statistical evidence for a contrast cannot be assessed. No treatment effect should be inferred from the endpoint definition, study purpose, or dosing sequence.

The design was open-label, non-randomized, single-group, and fixed-sequence. As a general design consideration, a comparison across assessment times in a fixed sequence is not equivalent to a randomized comparison between concurrent groups. The registry record does not describe an analysis that separates treatment condition from other changes over the study sequence. This limits the causal interpretation that can be made from the record.

The safety information is descriptive. Serious adverse events are listed for zero participants in each group, while other adverse events are listed for 1, 2, and 7 participants across the three group entries. The record does not provide the associated event terms or inferential comparisons. The death entries are null, and deaths are not reported in the registry record.

More broadly, the registry’s stated purpose and reported measurements concern pharmacokinetics in healthy adults. The posted information does not establish clinical benefit, clinical harm, or effects in a patient population. It also does not report enough information to evaluate the numerical pharmacokinetic result, its uncertainty, or the handling of missing data. The appropriate conclusion is limited to what the record documents: a study design and endpoint definition, enrollment, and selected adverse-event counts, without posted primary efficacy estimates.

13. Why This Trial Matters Statistically

This study is statistically useful as an example of how a pharmacokinetic question can be framed around exposure over a defined dosing interval. AUCtau integrates concentration over time, and the registry specifies tau as 12 hours. It also identifies a geometric mean and geometric coefficient of variation, illustrating that pharmacokinetic endpoints may be summarized on a multiplicative scale rather than only with arithmetic summaries.

The design highlights why comparison structure matters. The record labels the study non-randomized, open-label, single-group, and fixed-sequence. Its two named primary endpoint conditions occur on Day 3 and Day 17, rather than in concurrently randomized groups. General statistical interpretation therefore needs to distinguish a sequence of within-study assessments from a randomized treatment contrast. The registry record does not report how time or sequence effects were addressed analytically.

The record also demonstrates the difference between a clearly defined outcome and a reported result. The primary endpoint, units, summary type, dispersion measure, and relevant assessment days are described, but the numerical endpoint values and uncertainty estimates are not reported. Without those statistics, readers cannot quantify the observed contrast or its precision.

Finally, the adverse-event entries illustrate the limited role of descriptive counts when detailed event terms and comparative analyses are absent. The counts can be read as what the registry lists, but they do not themselves estimate causal differences between treatment conditions. These features make the study a useful case for separating design information, outcome definition, descriptive safety reporting, and inferential results.

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 principal limitation of interpreting this record is that it does not report numerical results for the primary endpoint. AUCtau is defined, and the assessment conditions are identified, but the geometric means, geometric coefficients of variation, between-condition estimate, confidence interval, and p-value are not reported in the registry record. The magnitude, direction, and precision of the pharmacokinetic contrast therefore cannot be assessed.

The design is listed as non-randomized, open-label, single-group, and fixed-sequence. The primary assessment conditions are tied to different study days. The record does not report an analysis method addressing possible time or sequence influences, and it does not provide a statistical analysis plan. This prevents assessment of how the comparison was modeled or what assumptions supported any estimate.

Although 13 participants were enrolled, the number contributing to the primary endpoint is not reported. The record defines the pharmacokinetic analysis population but does not give endpoint-specific denominators, missing-data counts, reasons for missingness, exclusions, or methods for handling incomplete measurements. The complete dosing schedule cannot be reconstructed from the arm description because its text is incomplete in the registry record.

Safety reporting is also limited: the serious-event term list is empty, other adverse-event counts are not accompanied by event terms, and death fields are null. The record does not explain the null entries. It also does not report a sample-size justification, interim analyses, or stopping rules. Each of these details is unreported, rather than evidence that a particular approach was or was not used outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of PF-04958242 in Healthy Subjects — NCT02341482.
• Registry record last updated 2020-01-09; status last verified 2019-12.
• Results first posted 2016-06-30.
• 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

NCT02341482 is a completed Phase 1, open-label, non-randomized, single-group, fixed-sequence study sponsored by Biogen. It enrolled 13 healthy adult subjects and was designed to characterize PF-04958242 pharmacokinetics when co-administered with itraconazole. The primary endpoint was AUCtau over a 12-hour dosing interval, summarized as a geometric mean with geometric coefficient of variation.

The endpoint description identifies PF-04958242 0.025 mg on Day 3 and PF-04958242 0.025 mg combined with itraconazole 200 mg on Day 17. The registry lists 13 outcome measures and zero analysis entries. It does not report numerical primary endpoint results, an estimated contrast, uncertainty estimates, or the statistical analysis plan.

Serious adverse events are listed for zero participants in each of three treatment group entries. Other adverse events are listed for 1, 2, and 7 participants, respectively. Deaths are not reported in the registry record. The available information supports a description of study design and posted counts, but not an estimate of the primary pharmacokinetic effect or its precision.