This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers (NCT02804399), a registered phase 1 study. The primary outcome is Plasma AUCinf for PF-06463922 Given Alone and With Rifampin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02804399 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Not Stated |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers who received PF-06463922 and rifampin. The registry record reports an enrollment of 12.
Intervention
A single oral dose of PF-06463922 100 mg given with rifampin 600 mg QD.
Comparator
A single oral dose of PF-06463922 100 mg given alone. The described schedule places the PF-06463922-alone period before the combination period, with at least 10 days between the two PF-06463922 doses.
Primary question
How does rifampin affect the plasma AUCinf of PF-06463922? AUCinf represents exposure over time, extrapolated from time 0 to infinite time. Numerical estimates for this comparison are not reported in the registry record.
The study was intended to estimate a pharmacokinetic effect, rather than compare clinical outcomes. Its primary endpoint was plasma AUCinf for PF-06463922 given alone and with rifampin. The registry describes sampling over time after dosing in each period. It also lists other pharmacokinetic outcomes, including AUClast, Tmax, half-life, clearance, and apparent volume of distribution for PF-06463922, along with outcomes for PF-06895751.
The design used the same participants in both treatment periods, which makes the question a within-participant comparison in principle. However, the registry does not report numerical primary outcome results, a treatment-effect estimate, or uncertainty around an estimate. It therefore does not establish from the posted record how large or precise any difference in exposure was. The allocation is not stated, and the listed arms are not a like-for-like randomized control comparison. Interpretation should focus on the design and the information actually reported, rather than treating the study as a conventional parallel-group efficacy trial.
3. Trial Design
This was a Phase One, open-label, two-period, two-treatment, fixed-sequence crossover study in healthy volunteers. The registry record reports enrollment of 12 and a completed study. The stated study dates are 2016-07 for start and 2016-10 for primary completion.
In the described sequence, participants received a single oral dose of PF-06463922 100 mg, followed by a single dose of PF-06463922 100 mg with rifampin 600 mg QD. At least 10 days separated the two PF-06463922 doses. The registry describes pharmacokinetic sampling after dosing in both periods. The primary outcome population is defined as participants who received PF-06463922 and rifampin in the respective periods; the number evaluable for the primary outcome is not reported in the registry record.
A crossover design measures each participant under more than one treatment condition. In general, this can make within-participant comparisons less affected by stable differences between people than comparisons of separate groups. This study’s fixed sequence means the PF-06463922-alone condition came before the combination condition; sequence order was not randomized according to the record. As a result, treatment condition and period are linked, so changes over time or residual effects could complicate interpretation. The stated washout period is part of the design, but the record does not report an assessment of carryover.
The study was open label, and the registry does not state allocation details beyond the fixed sequence. It lists separate safety groups for PF-06463922, rifampin, and the combination, but the arm description specifies the two PF-06463922 periods. The registry record does not explain the relationship between all safety groups and the dosing schedule in greater detail. The study is not described as a randomized comparison, and its arms should not be treated as equivalent parallel control groups.
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.
Period 1
| Stage | PF-06463922 100 mg Single Dose (SD) | Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD |
|---|---|---|
| STARTED | 12 | 0 |
| COMPLETED | 12 | 0 |
| NOT COMPLETED | 0 | 0 |
Washout Period at Least 10 Days
| Stage | PF-06463922 100 mg Single Dose (SD) | Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD |
|---|---|---|
| STARTED | 12 | 0 |
| COMPLETED | 12 | 0 |
| NOT COMPLETED | 0 | 0 |
Period 2
| Stage | PF-06463922 100 mg Single Dose (SD) | Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD |
|---|---|---|
| STARTED | 0 | 12 |
| COMPLETED | 0 | 11 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | PF-06463922 100 mg Single Dose (SD) | Rifampin 600 Once a Day (QD) + PF-06463922 100 mg SD |
|---|---|---|
| Adverse Event | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants who received PF-06463922, rifampin and PF-06463922 in Period 1 and 2, respectively. A washout period of at least 10 days between the 2 single PF-06463922 dose was maintained. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.
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.
| Characteristic | Unit | Entire Study |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 36.5 (SD 11.1) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma AUCinf for PF-06463922 Given Alone and With Rifampin, measured over Predose, 0.5, 1, 1.5, 2, 4, 6, 12, 24, 36, 48, 60, 72, 96, 120 hours postdose on Day 1 after PF-06463922 100 mg administration in Period 1, and at the same time points on Day 8 after PF-06463922 100 mg with rifampin administration in Period 2..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nanogram (ng)*hr/ millilitre (mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was plasma AUCinf for PF-06463922 given alone and with rifampin, reported as a geometric mean with geometric coefficient of variation. AUCinf is the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. It is used in pharmacokinetic research as a measure of overall drug exposure, incorporating measured concentrations over time and an extrapolated portion beyond the observed sampling period.
Comparing AUCinf under the two dosing conditions addresses whether coadministration is associated with a change in PF-06463922 exposure. That is a pharmacokinetic question, not a direct measure of clinical benefit or harm. The registry lists sampling from predose through 120 hours after dosing in the two periods. Extrapolation to infinite time means that the endpoint depends on both observed concentrations and the estimation of the terminal portion of the concentration-time profile.
A geometric mean is a summary suited to positive measurements that can vary multiplicatively. The geometric coefficient of variation describes relative spread on a multiplicative scale; it is not the same as a confidence interval and does not, by itself, show the precision of a treatment comparison. The numerical geometric means, variability estimates, and comparison uncertainty are not reported in the registry record. Consequently, the endpoint definition is available, but the observed magnitude and precision of the comparison cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the scientific question and the primary pharmacokinetic outcome, but it does not report the primary outcome values. There is no posted AUCinf estimate for either condition, no numerical treatment contrast, and no confidence interval or p-value for the comparison in the registry record described by the record. Accordingly, the direction, size, and precision of the observed pharmacokinetic effect cannot be stated from the registry record.
The within-participant crossover structure is relevant to interpretation. In a crossover study, each person can serve as their own reference, which in general helps control for stable participant characteristics. That benefit depends on valid measurement in both periods and on assumptions about period effects and residual treatment effects. The registry describes a fixed order, with PF-06463922 alone preceding PF-06463922 with rifampin, and a washout of at least 10 days between the two PF-06463922 doses. It does not report analyses of period or carryover effects, or information establishing whether the washout was sufficient for the pharmacokinetic comparison.
Because the order was fixed, treatment condition is not separated from period by randomized sequencing. Differences between periods could therefore reflect the treatment condition, time-related changes, or other period-specific influences. The record does not report an adjustment strategy that would clarify these possibilities. Open-label status is part of the design; pharmacokinetic concentrations are objective measurements, but the record does not describe blinding of laboratory personnel or other safeguards.
The registry lists a geometric mean and geometric coefficient of variation as the primary outcome summaries. Those summaries describe the distribution of exposure, but they do not substitute for a paired treatment estimate and its uncertainty. No such estimate is available in the registry record. The number enrolled is reported, but it should not be assumed that every enrolled participant contributed evaluable data to the primary endpoint. The record defines the analysis population but does not give the endpoint-specific number analyzed.
The safety listings are separate from the primary pharmacokinetic question. They report adverse-event counts for the listed groups, but these do not supply the missing AUCinf comparison and should not be used as evidence about the size of a pharmacokinetic effect. Likewise, the study’s Phase One setting and healthy-volunteer population define its scope; the record does not report clinical outcomes or establish implications for patients.
Overall, the record supports a description of the planned within-participant pharmacokinetic question and study structure. It does not support a numerical conclusion about how rifampin changed PF-06463922 exposure. Any interpretation of the effect’s magnitude or precision would require outcome results not reported in the registry record.
9. Statistical Methods Explained
What does a crossover design compare?
In general, a crossover design measures participants under more than one treatment condition. The comparison can use the fact that the same participant contributes observations under each condition, reducing the influence of stable differences between participants. This study describes two periods: PF-06463922 alone and PF-06463922 with rifampin. Its fixed sequence places the alone condition first. The record does not describe randomized treatment order.
A crossover analysis commonly focuses on within-participant contrasts rather than comparing unrelated group averages. That general approach depends on having usable measurements in both conditions and on considering effects of period and possible residual exposure from an earlier condition. Here the registry record does not report the statistical model, the specific contrast estimator, or methods for assessing period or carryover effects. These details are not reported in the registry record.
What does AUCinf represent?
Area under the concentration-time curve summarizes drug concentration over time. AUCinf extends the area from time 0 to infinite time, using observed concentration measurements and an extrapolated terminal part of the profile. In general, it is used to characterize overall systemic exposure. The registry describes scheduled sampling after each dose, but does not report the concentration values, the resulting AUCinf values, or the proportion of the estimate attributable to extrapolation.
The endpoint is expressed in nanogram (ng)*hr/ millilitre (mL). The record specifies a geometric mean and geometric coefficient of variation. A geometric mean summarizes positive measurements on a multiplicative scale. Geometric variation describes relative dispersion around that scale. Neither quantity alone provides a confidence interval for the difference between treatment conditions.
Why does uncertainty matter?
A treatment estimate describes the observed contrast; a confidence interval, in general, describes the range of values compatible with the data and the statistical procedure. Its width conveys precision, while its location conveys the direction and scale of the estimated effect. A p-value, when reported, addresses compatibility with a specified null model and is not a measure of effect size or clinical importance. The registry record does not report a confidence interval or p-value for the primary comparison. Therefore, neither statistical precision nor the result’s compatibility with a particular null hypothesis can be evaluated from the posted record.
Geometric summaries are often used when pharmacokinetic measures are right-skewed or vary proportionally. In general, analyzing log-transformed measurements can make multiplicative differences easier to model. However, the registry record does not state whether the analysis used a transformation, a particular model, or a specific method for deriving a treatment contrast. Those methods should not be inferred from the choice of geometric summary.
What is over-dispersion?
In general, over-dispersion means that observed variability exceeds what a statistical model assumes. If ignored, standard errors and uncertainty intervals can be misleading. This is a general statistical consideration, not a reported feature of this trial. The registry gives a geometric coefficient of variation as the primary outcome dispersion measure but does not report a model-based assessment of over-dispersion or any adjustment for it.
How should the fixed sequence affect interpretation?
In a randomized crossover, treatment order can be balanced or randomized to help distinguish treatment effects from period effects. In a fixed-sequence study, the order is set, so the treatment condition coincides with a particular period. In general, this can make it harder to distinguish a treatment-related change from a time-related change. A washout period is intended to reduce residual effects, but its presence alone does not demonstrate that carryover was absent. The study description specifies at least 10 days between PF-06463922 doses; an empirical carryover assessment is not reported in the registry record.
The open-label design means treatment assignment was not masked according to the registry. For an objective pharmacokinetic measure, the consequences of lack of masking may differ from those for subjective outcomes, but measurement and analysis procedures still matter. The record does not report whether laboratory staff or analysts were blinded, nor does it describe quality-control procedures.
What can the listed analysis information establish?
The registry reports 21 outcome measures and 3 analyses. Those listings indicate that multiple measures and analyses were registered, but they do not state how the primary outcome comparison was modeled or how results were selected for emphasis. The statistical analysis plan, any prespecified covariates, treatment of missing concentrations, rules for excluding pharmacokinetic profiles, and methods for multiplicity are not reported in the registry record. No inference should be made about those choices.
The record identifies an analysis population as participants who received the relevant treatments and had at least 1 primary-interest pharmacokinetic parameter in at least 1 treatment period. It also clarifies that the number analyzed denotes participants evaluable for the outcome. The endpoint-specific analyzed count is not reported. In general, missing data can affect crossover estimates particularly when incomplete observations prevent a within-participant contrast; the record does not explain how incomplete profiles were handled.
These general concepts help describe what would be relevant to evaluating a pharmacokinetic crossover analysis. They are not evidence that any particular model, diagnostic, missing-data procedure, or multiplicity adjustment was used in this study. The registry record does not report those details or the numerical primary results needed to judge the analysis empirically.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 21 outcome measures and 3 analyses. It names one primary outcome, plasma AUCinf for PF-06463922 given alone and with rifampin, as well as secondary pharmacokinetic outcomes for PF-06463922 and PF-06895751. The record does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for multiple comparisons. It is therefore not possible to determine from the record how the family of outcomes was handled statistically.
The primary outcome population is defined as participants who received PF-06463922 and rifampin in the respective periods, with at least 1 primary-interest pharmacokinetic parameter in at least 1 period. The registry states that the number analyzed is the number evaluable for the outcome, but the endpoint-specific number analyzed is not reported in the registry record. Enrollment alone does not establish how many participants contributed usable primary outcome measurements.
Methods for missing data, incomplete concentration profiles, exclusions, and handling of unevaluable pharmacokinetic parameters are not reported in the registry record. The record also does not state whether all analyses followed a prespecified statistical analysis plan, whether interim analyses occurred, or how the analysis population was applied to each outcome. These points should be treated as unknown rather than inferred from the crossover design or the enrollment figure.
In general, missing observations can affect a paired comparison when one condition is measured but the other is not. Incomplete reporting also limits the reader’s ability to assess whether the analysis population matches the planned question. Without endpoint-specific counts and analysis details, the completeness and robustness of the primary comparison cannot be judged from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| PF-06463922 100 mg | 0 | 12 | 0.0% |
| Rifampin 600 mg QD | 0 | 12 | 0.0% |
| Rifampin 600 mg + PF-06463922 100 mg | 5 | 12 | 41.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PF-06463922 100 mg | 1 of 12 |
| Rifampin 600 mg QD | 5 of 12 |
| Rifampin 600 mg + PF-06463922 100 mg | 11 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | PF-06463922 100 mg | Rifampin 600 mg QD | Rifampin 600 mg + PF-06463922 100 mg |
|---|---|---|---|---|
| Drug-induced liver injury | Hepatobiliary disorders | 0 of 12 | 0 of 12 | 5 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PF-06463922 100 mg | Rifampin 600 mg QD | Rifampin 600 mg + PF-06463922 100 mg |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 0 of 12 | 0 of 12 | 9 of 12 |
| Drug-induced liver injury | Hepatobiliary disorders | 0 of 12 | 0 of 12 | 7 of 12 |
| Dizziness | Nervous system disorders | 1 of 12 | 0 of 12 | 3 of 12 |
| Vomiting | Gastrointestinal disorders | 0 of 12 | 0 of 12 | 3 of 12 |
| Dry eye | Eye disorders | 0 of 12 | 1 of 12 | 1 of 12 |
| Photophobia | Eye disorders | 0 of 12 | 1 of 12 | 1 of 12 |
| Dyspepsia | Gastrointestinal disorders | 0 of 12 | 0 of 12 | 2 of 12 |
| Fatigue | General disorders | 0 of 12 | 1 of 12 | 1 of 12 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 12 | 0 of 12 | 2 of 12 |
| Abdominal pain | Gastrointestinal disorders | 0 of 12 | 0 of 12 | 1 of 12 |
Serious events with the highest arm-level rate: drug-induced liver injury (41.7%).
The registry lists serious adverse events by safety group. It reports 0 affected participants in the PF-06463922 100 mg group, 0 in the rifampin 600 mg QD group, and 5 in the rifampin 600 mg plus PF-06463922 100 mg group. Each group has 12 participants listed as at risk. These figures describe the registry’s safety listings; they do not provide a randomized like-for-like comparison, and the record does not establish that differences between groups are caused by treatment.
The record also lists other, non-serious adverse events: 1 affected participant for PF-06463922 100 mg, 5 for rifampin 600 mg QD, and 11 for the combination. These counts should be read separately from the serious-event counts. The listed top serious-event term is drug-induced liver injury, reported at 41.7%. The registry record does not make the denominator or the precise relationship of this term listing to the group-specific figures clear.
Death counts are not reported in the registry record. The adverse-event figures do not answer the primary pharmacokinetic question, and their small, non-randomized group structure limits comparative interpretation. They should be read as descriptive safety information in this record, not as a causal treatment comparison.
12. What the Result Does, and Does Not, Mean
This study addresses a focused pharmacokinetic question: whether PF-06463922 exposure, measured by plasma AUCinf, differed when the drug was given with rifampin rather than alone. The registry describes a fixed-sequence crossover in healthy volunteers, with a stated washout of at least 10 days between the PF-06463922 doses. It also defines the primary outcome and its analysis population.
The record does not report numerical AUCinf results, a treatment contrast, or uncertainty around that contrast. It therefore does not establish the direction, magnitude, or precision of any change in exposure. A geometric mean and geometric coefficient of variation are specified as outcome summaries, but their observed values are not reported in the registry record. No conclusion about the statistical significance of the primary comparison can be drawn from the available record.
The study is not a clinical-outcome trial. A pharmacokinetic measure describes drug exposure; it does not itself establish a clinical benefit or harm. The study enrolled healthy volunteers, and the record does not report patient outcomes. Its findings, even if numerical results were available, would need to be interpreted within that pharmacokinetic setting rather than assumed to answer questions about treatment outcomes in patients.
The design also limits what can be inferred. The fixed sequence links treatment condition with period, and the registry does not report an assessment of period or carryover effects. The posted safety counts are descriptive and do not create a randomized control comparison. These features make it important to distinguish the study’s intended question from claims that its record does not support.
In short, the record documents the study’s objective and methods at a high level but omits the primary outcome estimates needed to evaluate the observed pharmacokinetic effect. It should not be read as evidence for a particular size or direction of effect, nor as a direct statement about clinical effectiveness or safety in patients.
13. Why This Trial Matters Statistically
This trial illustrates how a small, within-participant pharmacokinetic study can be structured around a specific exposure question. Comparing PF-06463922 given alone with PF-06463922 given alongside rifampin focuses on pharmacokinetics rather than a clinical outcome. The crossover approach can, in general, reduce the influence of stable differences between participants because measurements come from the same individuals under both conditions.
The design also shows why sequence and period matter. A fixed sequence places one condition before the other, so treatment and period are not separated through randomized ordering. A washout is intended to address residual treatment effects, but the presence of a washout does not by itself demonstrate that carryover is absent. The record describes the sequence and washout but does not report a carryover assessment or a model that accounts for period.
Another statistical lesson is that endpoint definitions and summary measures are not a substitute for outcome estimates. The registry specifies AUCinf, a geometric mean, and a geometric coefficient of variation, but does not report the observed values or uncertainty for the comparison. Without those results, readers can understand what was intended to be measured but cannot assess the size or precision of the observed effect.
The registry also distinguishes an enrolled population from an endpoint-specific analysis population. It defines who could be considered evaluable, but does not report the number analyzed for the primary outcome or how incomplete data were handled. This limits assessment of how much information contributed to the comparison.
Finally, the listed safety groups and outcomes should not be mistaken for a randomized parallel-group trial. The record describes a fixed-sequence pharmacokinetic study and provides descriptive adverse-event counts. Understanding those distinctions helps keep conclusions aligned with the design and the results actually reported.
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 primary limitation for interpreting the pharmacokinetic question is that numerical primary outcome results are not reported in the registry record. AUCinf estimates, the treatment contrast, and uncertainty measures are unavailable, so the magnitude and precision of the comparison cannot be assessed.
The crossover sequence was fixed, with PF-06463922 alone preceding the combination period. Treatment and period are therefore linked in the design. Although the record specifies a washout of at least 10 days between the two PF-06463922 doses, it does not report whether carryover was assessed or describe an analysis accounting for period effects. Allocation is not stated, and the study is not a randomized comparison.
The registry defines the primary analysis population but does not report the number analyzed for the primary endpoint. It also does not describe missing-data procedures, handling of incomplete pharmacokinetic profiles, exclusions, or the statistical model. Details of any multiplicity strategy are not reported despite the listing of multiple outcome measures and analyses. The statistical analysis plan is not reported in the registry record.
The study was open label and conducted in healthy volunteers. The registry does not describe whether laboratory staff or analysts were masked, and no clinical outcome results are reported. These factors limit interpretation of the study’s scope and do not support conclusions about patient outcomes.
The safety listings are descriptive, and the registry does not establish a like-for-like randomized control comparison among the listed groups. The record’s serious-event term listing does not specify its denominator or clearly connect it to the group-specific counts. Death counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study To Evaluate The Effect Of Rifampin On Pharmacokinetics Of PF-06463922 In Healthy Volunteers — NCT02804399.
- Registry record last updated 2019-01-25; status last verified 2018-08.
- Results first posted 2019-01-25.
- 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.
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18. Record Summary
NCT02804399 is a completed Phase One, open-label, two-period, two-treatment, fixed-sequence crossover study in healthy volunteers. The registry reports enrollment of 12, a start in 2016-07, and primary completion in 2016-10. The study examined PF-06463922 given alone and with rifampin.
The primary outcome was plasma AUCinf for PF-06463922 under the two conditions, summarized as a geometric mean with geometric coefficient of variation. The record defines the analysis population and describes pharmacokinetic sampling, but does not report the primary numerical estimates or their uncertainty. It also does not report the primary endpoint-specific number analyzed or the statistical model.
The registry lists secondary pharmacokinetic outcomes and descriptive safety counts. Its fixed sequence and non-randomized comparison structure should be kept in mind when interpreting those listings. The posted record describes the intended pharmacokinetic question, but does not permit a numerical assessment of the primary treatment effect.