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 Estimation Of Effect Of Rifampin On Pharmacokinetics Of Crizotinib In Healthy Volunteers (NCT01147055), a non-randomized phase 1 study. The primary outcome is Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01147055 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers. The registry record lists an enrollment of 15. The primary pharmacokinetic analysis population is defined as enrolled and treated participants with at least one primary-interest pharmacokinetic parameter in at least one treatment period; the number included in that analysis is not reported in the registry record.
Intervention
Crizotinib given in the context of multiple-dose rifampin exposure. The treatment-group label specifies crizotinib 250 mg with rifampin 600 mg. The detailed rifampin dosing schedule is not reported in the registry record.
Comparator
Crizotinib 250 mg without rifampin, as identified by the other treatment-group label. This is a nonrandomized fixed-sequence crossover study, not a randomized comparison between independent groups. The treatment-order details beyond the fixed-sequence designation are not reported in the registry record.
Primary question
How does multiple-dose rifampin exposure relate to the pharmacokinetics of a single crizotinib dose in healthy volunteers? The designated primary measure is crizotinib area under the plasma concentration-versus-time curve from time zero to extrapolated infinite time. The registry record does not report the estimated effect or its precision.
The question is about drug exposure, not a clinical disease outcome. The record identifies healthy volunteers as the study population and lists pharmacokinetic measures for crizotinib and its metabolite. It does not report a clinical benefit or harm comparison, and the results needed to describe the magnitude or direction of the primary pharmacokinetic contrast are not reported in the registry record.
3. Trial Design
This was a Phase 1, nonrandomized, unmasked, fixed-sequence crossover study sponsored by Pfizer. The registry record lists the study as completed, with a start in 2010-07 and primary completion in 2010-10. It lists 15 enrolled participants and describes the population as healthy volunteers.
A crossover design evaluates more than one treatment condition in the same participant, allowing within-participant comparisons when measurements are available in both conditions. That general feature can reduce the influence of stable differences between people. It does not, by itself, ensure that treatment conditions are comparable: order, time effects, carryover, incomplete measurements, and other design details can matter. Here, allocation is listed as nonrandomized and masking as none. Therefore, the comparison should not be described as randomized or blinded.
The registry describes a fixed-sequence crossover and specifies that there should be at least a 14-day washout period between treatment A and B. The exact sequence details and the operational definition of treatment A and treatment B are not reported in the registry record. The record also does not describe adherence procedures or the detailed schedule for rifampin administration.
The treatment-group labels identify crizotinib 250 mg alone and crizotinib 250 mg with rifampin 600 mg. The primary endpoint is measured after crizotinib dosing in period 1 and period 2. Listed sampling times extend from predose through 144 hours after the crizotinib dose in each period. The record includes additional pharmacokinetic outcomes for crizotinib and its metabolite, but it does not provide the numerical outcome results.
The study is not a randomized parallel-group trial. Its treatment-group labels and adverse-event risk sets should therefore be read as descriptions of treatment conditions, not as evidence of independent randomized arms. The record does not report a detailed statistical analysis plan, a sample-size justification, or whether interim analyses were planned.
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.
First Intervention Period
| Stage | Crizotinib 250 mg | Crizotinib 250 mg + Rifampin 600 mg |
|---|---|---|
| STARTED | 15 | 0 |
| COMPLETED | 14 | 0 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Crizotinib 250 mg | Crizotinib 250 mg + Rifampin 600 mg |
|---|---|---|
| Lost to Follow-up | 1 | 0 |
Washout Period (at Least 14 Days)
| Stage | Crizotinib 250 mg | Crizotinib 250 mg + Rifampin 600 mg |
|---|---|---|
| STARTED | 14 | 0 |
| COMPLETED | 14 | 0 |
| NOT COMPLETED | 0 | 0 |
Second Intervention Period
| Stage | Crizotinib 250 mg | Crizotinib 250 mg + Rifampin 600 mg |
|---|---|---|
| STARTED | 0 | 14 |
| COMPLETED | 0 | 14 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
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 Population |
|---|---|---|
| Participants analysed | 15 | |
| Age Continuous | years | 38.9 (SD 8.5) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)], measured over 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose in period 1 and Day 0, 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Deviation |
| Unit | ng*hr/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is area under the plasma concentration-versus-time curve from time zero to extrapolated infinite time, abbreviated AUC (0 - ∞). It is a pharmacokinetic measure of total systemic exposure over time after a dose. The record defines it as the area from time zero to the last measured time plus the estimated area from that time to infinity. The measurement unit is ng*hr/mL.
In general, concentration measurements taken over time trace how drug levels change after dosing. AUC combines information across that curve rather than focusing on a single sampling time. Extrapolation to infinite time extends the exposure estimate beyond the last quantifiable concentration, so the estimate depends partly on the observed concentrations and partly on the terminal portion of the curve.
The endpoint is suitable for a pharmacokinetic question because it represents overall exposure, while other measures can describe particular aspects of the concentration profile. The registry lists AUClast, maximum-concentration timing, plasma decay half-life, apparent oral clearance, and apparent volume of distribution among secondary outcomes. It also lists AUC and maximum-concentration timing measures for the crizotinib metabolite.
The primary outcome is described as a geometric mean with standard deviation as the dispersion measure. The registry record does not report the numerical geometric means, a treatment contrast, a confidence interval, or a p-value. It therefore does not permit a quantitative statement about the size, direction, or precision of the primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a focused pharmacokinetic question: the effect associated with multiple-dose rifampin exposure on the pharmacokinetics of a single crizotinib dose in healthy volunteers. It specifies AUC (0 - ∞) as the primary measure and describes a fixed-sequence crossover design. However, the numerical primary results are not reported in the registry record. The effect's direction and magnitude, and the uncertainty around any contrast, cannot be stated from this record.
The endpoint description establishes what was intended to be measured, not what was observed. AUC (0 - ∞) represents exposure over the concentration-time curve, with an extrapolated component after the final measured time. Without the reported outcome values or a treatment contrast, readers cannot assess whether the values differed between treatment periods or how precisely any difference was estimated. The record also does not report a confidence interval or test result for the primary comparison.
The design warrants care in interpreting any comparison. In general, a crossover can support within-participant comparisons, but a fixed sequence and nonrandomized allocation do not provide the protection against order-related differences that random assignment can offer. The listed washout interval is a design detail; it does not establish, on its own, whether carryover was absent. The registry record does not report analyses or diagnostics addressing period effects, carryover, or sequence effects.
The adverse-event record lists no serious adverse events in either treatment condition: 0 among 15 at risk for crizotinib 250 mg and 0 among 14 at risk for crizotinib 250 mg plus rifampin 600 mg. It lists 3 participants with other adverse events in each condition. These are descriptive registry entries, not a formal comparative safety analysis. Death counts are not reported in the registry record.
Planning illustrations based on an observed effect are not observed trial results, and they are not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. Those assumptions describe an illustration rather than the study's crossover design; the registry record does not report the trial's sample-size justification.
Overall, the available record supports a description of the study question, endpoint, design, and selected safety counts. It does not support a conclusion about the estimated pharmacokinetic effect, its statistical significance, or the precision of that effect. Such conclusions require outcome results that are not reported in the registry record.
9. Statistical Methods Explained
What does the primary measure capture?
In general, pharmacokinetic sampling measures drug concentration at planned times after dosing. Plotting concentration against time gives a curve that changes as the drug enters and leaves the measured compartment. AUC summarizes the area under that curve. AUC (0 - ∞) includes the observed portion through the final quantifiable time and an extrapolated portion beyond it. The registry record names this as the primary endpoint and lists sampling from predose through 144 hours in each treatment period.
The extrapolated tail is not a direct observation extending indefinitely. It is an estimate based on the measured concentration profile and the terminal decay pattern. In general, the reliability of an AUC extrapolation depends on the quality and duration of sampling and on how well the terminal pattern is characterized. The registry record does not give the fraction of the endpoint that was extrapolated or details of the calculation beyond its definition.
Why use a geometric mean?
In general, pharmacokinetic measurements are often summarized using geometric means because exposure values can vary multiplicatively. A geometric mean is calculated on a logarithmic scale and then expressed on the original scale; it describes a typical multiplicative level rather than an arithmetic average. The registry record identifies the primary parameter as a geometric mean and names standard deviation as its dispersion measure. It does not report whether values were transformed for analysis, how the dispersion was calculated, or which inferential method was used.
A dispersion measure describes variability in observations, while a confidence interval describes uncertainty in an estimated quantity. They answer different questions. A standard deviation is not a substitute for a confidence interval for a treatment contrast. Since neither numerical outcome summaries nor a contrast interval are reported in the registry record, the precision of the primary comparison cannot be assessed from the available results.
How does a crossover comparison work?
In general, a crossover design measures participants under more than one treatment condition. A paired analysis uses the within-participant relationship between those measurements, rather than treating each condition as if it came from a separate set of unrelated people. This can account for stable characteristics that differ across participants. The record identifies a fixed-sequence crossover, but it does not report the analysis model or whether the reported comparison, if any, used paired data.
Sequence and period can matter in a crossover. Period effects are changes over time that could affect measurements regardless of treatment. Carryover occurs when an earlier treatment may still affect measurements during a later period. A washout interval is intended to separate treatment periods, but its presence alone does not demonstrate that carryover was eliminated. The registry record specifies a washout of at least 14 days between treatment A and B, but does not report testing or adjustment for period or carryover effects.
The record lists nonrandomized allocation and no masking. These are relevant to how confidently a contrast can be attributed to the treatment condition. In general, an unmasked design can allow expectations or study procedures to influence measurement or reporting, although objective concentration measurements may be less dependent on subjective judgment. The record does not describe safeguards or provide information to assess such influences. No causal interpretation beyond the measured pharmacokinetic comparison is warranted from the design description alone.
What do significance tests and intervals mean?
In general, a significance test evaluates how compatible data are with a specified null hypothesis under the assumptions of the analysis. A p-value is not the probability that a treatment has no effect, and it does not measure the size or clinical importance of an effect. A confidence interval describes a range of estimates compatible with the data and model at the stated confidence level. It conveys precision as well as the direction and scale of an estimated contrast.
The registry record does not report a primary contrast, confidence interval, or p-value. Therefore, no statement about statistical significance or precision can be made. A geometric mean and a standard deviation alone, even if numerical summaries were available, would not necessarily reproduce a crossover treatment contrast; the within-participant pairing and analysis method can be important.
What is over-dispersion, in general?
Over-dispersion means that observed variability is greater than a statistical model assumes. It is especially relevant for count outcomes when counts vary more widely than a basic Poisson model allows. A model that ignores over-dispersion can understate uncertainty. The primary endpoint is a continuous pharmacokinetic measure, not a count outcome, and the record does not describe an over-dispersion model. This general concept does not supply an analysis method for this trial.
How should planning estimates be read?
Sample-size calculations are planning exercises that ask how many participants would be needed under specified assumptions to detect an effect with a chosen design and operating characteristics. The registry's stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with a target effect expressed as a fraction of the observed effect. Such estimates are hypothetical planning quantities, not observed power and not evidence that the trial was designed around those assumptions.
The illustration's equal-allocation, two-arm framing is not the same as a fixed-sequence crossover, where within-participant measurements and their correlation may affect precision. The trial's own sample-size justification and detailed statistical plan are not reported in the registry record. Without the outcome contrast and its variability, the planning illustration cannot establish the observed precision of the trial result.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 14 outcome measures and 6 analyses. It identifies AUC (0 - ∞) for crizotinib as the primary outcome and lists additional pharmacokinetic measures for crizotinib and its metabolite. These include AUC measures, time to maximum observed plasma concentration, half-life, apparent oral clearance, and apparent volume of distribution. The record does not explain how the six analyses map to the outcome measures or which analyses were designated confirmatory.
When multiple outcomes or comparisons are tested, the chance of at least one false-positive finding can increase. General approaches include prespecifying a primary outcome, adjusting significance thresholds, or treating secondary analyses as exploratory. Whether any multiplicity adjustment was used is not reported in the registry record. The record also does not report a detailed statistical analysis plan, so the planned hierarchy of outcomes and tests cannot be assessed.
The primary pharmacokinetic analysis population is defined as all enrolled and treated participants with at least one primary-interest pharmacokinetic parameter in at least one treatment period. The number included in this population is not reported in the registry record. The record does not describe the handling of missing samples, incomplete periods, values below quantification limits, protocol deviations, or exclusions from individual analyses. It does not report whether missing values were imputed or whether sensitivity analyses were conducted.
In general, missing measurements can affect a crossover comparison if availability differs by period or treatment condition. A participant with measurements from only one period may contribute to some summaries but not to a complete paired contrast, depending on the analysis. The registry's population definition allows inclusion with a primary parameter from at least one period, but the actual analysis set and missing-data methods are not reported in 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 |
|---|---|---|---|
| Crizotinib 250 mg | 0 | 15 | 0.0% |
| Crizotinib 250 mg + Rifampin 600 mg | 0 | 14 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Crizotinib 250 mg | 3 of 15 |
| Crizotinib 250 mg + Rifampin 600 mg | 3 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Crizotinib 250 mg | Crizotinib 250 mg + Rifampin 600 mg |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 2 of 15 | 1 of 14 |
| Constipation | Gastrointestinal disorders | 0 of 15 | 2 of 14 |
| Nausea | Gastrointestinal disorders | 1 of 15 | 0 of 14 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 15 | 0 of 14 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 0 of 14 |
| Eye swelling | Eye disorders | 0 of 15 | 0 of 14 |
| Headache | Nervous system disorders | 0 of 15 | 0 of 14 |
The adverse-event entries list 0 serious adverse events among 15 participants at risk for crizotinib 250 mg and 0 among 14 at risk for crizotinib 250 mg plus rifampin 600 mg. The registry also lists 3 participants with other adverse events in each treatment condition. No serious adverse-event terms are listed. These are descriptive counts in the registry record; they do not provide a statistical comparison or establish that the conditions have identical safety profiles.
The study is a nonrandomized crossover, so these treatment-condition entries should not be interpreted as results from independent randomized groups. The registry does not provide event descriptions for the other adverse events, their severity, timing, relationship to treatment, or whether the same participant contributed an event under more than one condition. Such details are not reported in the registry record.
Deaths are recorded as not reported in the registry record. A blank or unreported death count cannot be interpreted as a confirmed absence of deaths. The safety entries also do not quantify the uncertainty around rare events. In general, observing no serious events in a study does not establish that the risk is zero, particularly when the study is designed around pharmacokinetic measurements rather than a precise safety estimate.
12. What the Result Does, and Does Not, Mean
The study addresses a pharmacokinetic question in healthy volunteers: how multiple-dose rifampin exposure relates to crizotinib exposure after a single dose. The registry record identifies AUC (0 - ∞) as the primary endpoint and describes a fixed-sequence crossover. It also lists several secondary pharmacokinetic outcomes for crizotinib and its metabolite. This information establishes the study's focus, but it is not a report of the primary treatment effect.
The primary numerical results are not reported in the registry record. Consequently, the direction and magnitude of any difference in AUC cannot be stated, and neither statistical significance nor precision can be evaluated. The record does not provide a confidence interval, p-value, or numerical contrast. No conclusion about the size of an effect follows solely from the stated endpoint, treatment labels, or design.
Even with numerical pharmacokinetic results, a measured exposure contrast would address drug concentration behavior under the studied conditions. It would not, by itself, establish a clinical outcome or answer questions about people with a particular illness. This study enrolled healthy volunteers, and the registry record does not describe clinical disease outcomes.
The record's safety counts are also limited descriptive information. It lists no serious adverse events in either treatment condition and lists other adverse events in both. These entries do not establish comparative safety, and death counts are not reported in the registry record. The study's size and pharmacokinetic focus do not turn these counts into a comprehensive assessment of uncommon harms.
Finally, design features affect interpretation. This is a nonrandomized, unmasked, fixed-sequence crossover, with a specified washout interval. The record does not provide enough information to assess period or carryover effects, the exact treatment sequence, or the analysis approach. The appropriate conclusion is therefore narrow: the registry describes a study intended to estimate a pharmacokinetic effect, but does not report the result needed to quantify that effect.
13. Why This Trial Matters Statistically
This trial is statistically notable because it uses a crossover structure to investigate pharmacokinetics. In general, repeated measurements within participants can make treatment-condition comparisons more informative by accounting for stable differences between people. That advantage depends on suitable analysis of paired measurements and on design conditions such as manageable period effects and limited carryover.
The registry record identifies a fixed sequence and nonrandomized allocation. Those details matter because treatment order is not described as randomized, and order-related influences may be difficult to separate from treatment effects. A washout interval is specified, but its presence does not demonstrate that carryover was absent. The record does not report analyses of these potential design effects.
The primary endpoint also illustrates a common pharmacokinetic distinction: AUC (0 - ∞) summarizes exposure over a concentration-time profile, including an extrapolated tail. This is not the same as a single concentration at one time. The endpoint's interpretation depends on the measured profile and the estimation of exposure after the final quantifiable measurement.
The record's outcome list shows that the study considered several aspects of pharmacokinetics, including exposure, concentration timing, and clearance-related measures, as well as metabolite measures. Multiple outcomes raise questions about which findings were primary and how other analyses were treated. The multiplicity strategy is not reported in the registry record.
Finally, this record demonstrates the distinction between a clearly described question and an interpretable numerical result. The trial's design, population, and primary measure are identified, but the primary estimate and its uncertainty are not reported. Without those values, statistical interpretation must remain limited to design and measurement rather than the size or precision of the observed effect.
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 main limitation for interpreting the pharmacokinetic question is that the primary result is not reported in the registry record. No numerical AUC summary, treatment contrast, confidence interval, or p-value is available in the record. The effect's direction, magnitude, and precision therefore cannot be evaluated.
The design is nonrandomized, unmasked, and fixed-sequence. The registry specifies at least a 14-day washout between treatment A and B, but the exact sequence details and evidence concerning carryover or period effects are not reported. The analysis model and the handling of within-participant pairing are also not reported in the registry record.
The primary analysis population is defined by availability of at least one primary-interest pharmacokinetic parameter in at least one period, but the number analyzed is not reported. Missing-data methods, exclusions, adherence information, and sensitivity analyses are not reported. These omissions prevent assessment of how incomplete measurements may have influenced the comparison.
The record lists multiple outcome measures and analyses but does not report a multiplicity approach or detailed analysis plan. It also does not report the trial's sample-size justification. The stated planning illustration uses assumptions that do not match the crossover design, and planning estimates should not be mistaken for observed precision or observed power.
Generalizability is limited by the recorded population: healthy volunteers. The record does not provide clinical outcome results. Safety reporting is also limited to selected adverse-event counts; descriptions of other events and death counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Estimation Of Effect Of Rifampin On Pharmacokinetics Of Crizotinib In Healthy Volunteers — NCT01147055.
- Registry record last updated 2011-10-24; status last verified 2011-10.
- Results first posted 2011-10-19.
- 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
The registry record describes NCT01147055, a completed Phase 1, nonrandomized, unmasked, fixed-sequence crossover study sponsored by Pfizer. It lists 15 enrolled healthy volunteers, a start in 2010-07, and primary completion in 2010-10.
The study's primary endpoint is crizotinib AUC (0 - ∞), measured after dosing in two treatment periods. Treatment labels identify crizotinib 250 mg alone and crizotinib 250 mg with rifampin 600 mg. The record specifies at least a 14-day washout between treatment A and B.
The primary pharmacokinetic estimate and its uncertainty are not reported in the registry record. Safety entries list 0 serious adverse events in each treatment condition and 3 participants with other adverse events in each; death counts are not reported.