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 An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B (NCT02213250), a na phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02213250 |
| Phase | Phase 1 |
| Condition | Hemophilia B |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Male Chinese subjects with hemophilia B. The registry lists an enrollment of 12 and states that all participants were included in the pharmacokinetic analysis population.
Intervention
A single dose of BeneFIX, listed as 50 IU/kg. BeneFIX is identified as recombinant factor IX.
Comparator
None is listed. The study is described as single group, with allocation recorded as not applicable and no masking.
Primary question
What was the maximum observed plasma concentration of BeneFIX, measured in IU/milliliter (IU/mL), after dosing at the scheduled pharmacokinetic sampling times?
This is a pharmacokinetic question about observed drug concentration after administration, rather than a comparison of treatment effects between groups. The primary endpoint is maximum observed plasma concentration, abbreviated Cmax in the registry. The planned sampling schedule ran from pre-dose through 96 hours post-dose, with measurements at 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose.
The registry also lists safety and tolerability outcomes, including treatment-emergent adverse events, serious adverse events, withdrawals due to adverse events, laboratory measurements, vital signs, inhibitor development, allergic reactions and thrombogenicity. Those outcomes address different questions from Cmax: they concern events or measurements observed after treatment rather than the concentration profile itself. Their inclusion does not make the study a controlled comparison, and the registry does not list a comparator group.
The registry describes the study as open-label and single-dose. It was completed, and its stated purpose was to assess pharmacokinetics in a China study supporting registration in China. The record does not report a comparative clinical-benefit question or a treatment-effect estimate.
3. Trial Design
The registry describes NCT02213250 as a completed phase 1, open-label, single-dose pharmacokinetic study. It lists a single-group model, allocation as not applicable and masking as none. The intervention is BeneFIX, with the treatment group titled BeneFIX 50 IU/kg. No control arm or randomized allocation is listed, so the design does not support a like-for-like comparison between treatment groups.
Enrollment was 12. The registry’s brief summary says this sample size was based on a CFDA requirement for a China pharmacokinetic study and to support registration in China. It does not report a statistical sample-size justification based on a target precision for Cmax, a minimum detectable difference or a planned power calculation. Any sample-size illustrations elsewhere are planning exercises, not descriptions of how the study’s enrollment was determined.
The study began in 2015-03, reached primary completion in 2015-04 and is marked completed. These dates describe the registry record; the detailed visit schedule, treatment administration procedures and the timing of safety follow-up beyond the listed pharmacokinetic sampling times are not reported in the registry record.
The primary endpoint is maximum observed plasma concentration, expressed in IU/milliliter (IU/mL). Sampling was scheduled pre-dose and at 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose. The primary endpoint is specified as a geometric mean with geometric coefficient of variation as its dispersion measure. The pharmacokinetic analysis population is defined as participants enrolled and treated who had at least 1 of the primary-interest pharmacokinetic parameters; the record states that all participants were included in that population.
Safety outcomes are also listed, including adverse events, laboratory and vital-sign findings, inhibitor development, allergic reactions and thrombogenicity. The record lists 16 outcome measures and no analysis records. It does not describe a randomization scheme, masking procedures, a comparator, or a statistical analysis plan in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants did not receive an infusion of any FIX products for at least 4 days and were required to be in a non-bleeding state before the administration of BeneFIX on Day 1.
Overall Study
| Stage | BeneFIX 50 IU/kg; Age Group: >=6 and <12 Years | BeneFIX 50 IU/kg; Age Group: >=12 Years |
|---|---|---|
| STARTED | 4 | 8 |
| COMPLETED | 4 | 8 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: All participants were included in the baseline population.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | Years | 24.8 (SD 15.4) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax), measured over Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | IU/milliliter (IU/mL) |
| Endpoint classification | not reduced to a single comparison |
Maximum observed plasma concentration, or Cmax, is the highest measured plasma concentration recorded for a participant across the scheduled post-dose sampling times. In this study it is expressed in IU/milliliter (IU/mL). The registry specifies a geometric mean for the endpoint and a geometric coefficient of variation to describe dispersion.
As a general pharmacokinetic concept, Cmax describes the observed peak concentration in a sampling profile. It is useful for characterizing exposure after administration, while other pharmacokinetic measures can describe different features, such as how concentration changes over time. Cmax does not by itself summarize the whole concentration-time profile, and it is not a direct measure of a clinical outcome.
The measurement depends on the sampling schedule: a peak between scheduled draws may not be captured as the observed maximum. The registry lists pre-dose sampling and post-dose measurements at 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours. The actual measured Cmax, its geometric coefficient of variation and any confidence interval are not reported in the registry record. Therefore, the endpoint definition and schedule can be described, but the size and precision of the observed concentration result cannot be evaluated from the reported result information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a pharmacokinetic endpoint and describes the population, dose and sampling schedule, but it does not report the numerical Cmax result. It therefore does not establish what maximum concentration was observed, how much participant-to-participant variability was present, or how precisely the geometric mean was estimated. These are central details for interpreting the primary endpoint, and they are not reported in the registry record.
The registered endpoint is a geometric mean rather than an arithmetic mean. As a general statistical explanation, a geometric mean summarizes measurements on a multiplicative scale and can be suitable when positive values have a skewed distribution. Its interpretation differs from an arithmetic average: it describes a central value on a ratio-oriented scale. The registry also names geometric coefficient of variation as the measure of dispersion. Without the reported estimate, neither the central concentration nor the spread around it can be assessed.
The study has a single group and no comparator. Accordingly, the design describes pharmacokinetic observations after the listed BeneFIX dose; it does not estimate a contrast against another treatment, dose or untreated group. The registry does not report a treatment-effect estimate or comparative analysis. An absence of a comparator is not evidence that a comparison would have shown no difference; it means that such a contrast is not part of the listed design.
The safety listing reports 0 participants with serious adverse events among 12 at risk and 0 participants with other adverse events among 12 at risk. These are observed counts in this study group. They do not quantify the frequency of uncommon events with high precision, and the registry does not report deaths in the adverse-event summary. Counts for each separately listed safety outcome, such as withdrawals due to adverse events, are not reported in the registry record.
The enrollment rationale stated in the registry is a CFDA requirement for a China pharmacokinetic study and support for registration in China. That rationale is distinct from a precision-based statistical justification. The record does not state a target confidence-interval width or a target difference for Cmax. A planning illustration based on an observed effect cannot substitute for a prespecified design rationale, and it is not observed power.
Overall, the posted information describes the study’s purpose and design, and gives limited adverse-event counts. It does not give the primary pharmacokinetic estimate or enough inferential detail to judge its precision. Conclusions should remain limited to the design and the specific counts that are reported.
9. Statistical Methods Explained
The primary endpoint is a participant-level maximum observed concentration. In general, a pharmacokinetic profile consists of concentration measurements taken at scheduled times after administration. For each participant, the observed maximum is the largest measured value in that profile. The registry lists pre-dose and post-dose sampling through 96 hours, so the endpoint is tied to those observation times. It is an observed peak, not necessarily the exact peak that would be found if concentration were measured continuously.
What does the geometric mean describe?
The registry specifies that Cmax is summarized as a geometric mean. As a general statistical explanation, the geometric mean is calculated on a logarithmic scale and then expressed back on the original scale. This makes it a central summary suited to positive measurements whose variation is better described in multiplicative rather than additive terms. It should not be read as the arithmetic average. The registry record does not describe the distribution of individual Cmax values or explain why this summary was selected.
The dispersion measure is geometric coefficient of variation. In general, a coefficient of variation relates spread to the scale of the measurements, and the geometric version is appropriate to summaries formed on a multiplicative scale. It helps describe how variable participant measurements are relative to the central estimate. It is not a confidence interval: dispersion among participants and uncertainty about an estimated mean answer different questions. The numerical geometric mean and geometric coefficient of variation are not reported in the registry record.
What would a confidence interval add?
In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis method. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. It does not show the range containing every participant’s value. No confidence interval for Cmax is reported in the registry record, and the analysis method used to obtain uncertainty estimates is not described. The estimate’s precision therefore cannot be assessed from the registry information.
How should the single-group design affect interpretation?
A single-group study can describe measurements observed after the study intervention, but it does not provide a concurrent control-group contrast. In general, a comparison between groups helps separate differences associated with treatment from differences that could arise from participant characteristics, time or other influences. Here, the record lists no comparator, allocation is not applicable, and masking is none. The endpoint should therefore be interpreted descriptively within the study group rather than as evidence of a difference versus another intervention.
The registered analysis population includes participants enrolled and treated who had at least 1 primary-interest pharmacokinetic parameter; the registry states that all participants were included in the pharmacokinetic analysis population. This definition identifies who is intended for the primary analysis, but it does not explain how incomplete profiles, missing concentration values or measurements outside an expected range were handled. Those procedures are not reported in the registry record.
What do the planning assumptions mean?
The sample-size illustrations are described as planning calculations based on an observed effect, not as the design calculation for this study. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the planned effect is a stated proportion of the observed effect. These are hypothetical planning assumptions for future comparisons. They do not convert this single-group study into a randomized comparison, and they do not describe the basis for its enrollment of 12.
In general, a sample-size calculation estimates how many participants a future study might need under chosen assumptions about variability, target effect, significance level and desired power. A planning estimate is conditional on those assumptions. It is not a measure of the probability that the completed study found a true effect, and it is not observed power. Because the record does not report the primary Cmax result or the numerical planning outputs, no numerical precision or sample-size conclusion can be drawn from those illustrations.
Why can extra variation matter?
In general, over-dispersion means that observed variability is greater than a statistical model assumes. If a model understates variability, its standard errors and uncertainty intervals may be too small, making results appear more precise than they are. The registry does not report a model-based analysis of Cmax, an assessment of over-dispersion or a method for adjusting for it. For a geometric summary, the pattern of variation and the scale of analysis matter; those details cannot be reconstructed from the endpoint label alone.
The record lists 16 outcome measures but no analysis records. It does not describe whether the primary endpoint was analyzed using a particular transformation, model, estimation method or missing-data procedure. These omissions limit the ability to reproduce the analysis or assess whether the method matched the observed data. General explanations of these statistical concepts do not establish which procedures were actually used in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 16 outcome measures, including the primary Cmax endpoint and secondary safety outcomes. It lists no analysis records. The record does not report a plan for controlling multiplicity across endpoints, time points or safety outcomes, nor does it specify a hierarchy for interpreting multiple statistical tests. A multiplicity adjustment, if used, is not reported in the registry record.
Multiplicity is a general statistical concern when many hypotheses are tested: the chance of at least one apparently unusual result can increase as the number of tests grows. Different approaches can control different error rates, but the appropriate approach depends on the study’s objectives and analysis plan. The registry does not provide enough information to determine whether formal testing was planned or performed. The number of outcome measures alone does not show that every outcome was tested or that an adjustment was necessary.
The primary pharmacokinetic analysis population is defined as participants enrolled and treated who had at least 1 primary-interest pharmacokinetic parameter. The record states that all participants were included in this population. It does not report how missing concentration measurements, incomplete sampling profiles, withdrawals, protocol deviations or values requiring special handling were treated. Imputation methods and sensitivity analyses are not reported in the registry record.
The adverse-event summary uses 12 participants at risk for serious events and 12 at risk for other events. The registry does not describe whether safety analyses used a different population definition or how time at risk was defined. It also does not report endpoint-specific missingness or outcome-level analysis results for the separately listed safety measures. These gaps mean the analysis populations and missing-data handling can be described only to the extent stated in the 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 |
|---|---|---|---|
| BeneFIX 50 IU/kg | 0 | 12 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.05% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BeneFIX 50 IU/kg | 0 of 12 |
The registry’s adverse-event summary lists 12 participants at risk for serious adverse events, with 0 affected, and 12 at risk for other adverse events, with 0 affected. These are counts for the BeneFIX 50 IU/kg group. They are observed counts in this study, not estimates of risk from a controlled comparison.
As a general statistical point, a count of zero does not establish that an event is impossible or that its underlying rate is zero. With a limited study enrollment, uncommon events may not occur among the participants observed. The registry does not report a confidence interval for these counts or a comparison group that would allow a relative safety contrast.
The listed secondary outcomes include treatment-emergent adverse events, serious adverse events and withdrawals due to adverse events, as well as laboratory, vital-sign and other safety measures. The summary counts do not provide separate results for each of these listed outcomes. Deaths are not reported in the registry record. The counts should therefore be read narrowly: they describe the serious and other adverse-event summary entries, rather than proving the absence of every possible safety event.
12. What the Result Does, and Does Not, Mean
The registry supports a description of a completed, open-label, single-dose, phase 1 pharmacokinetic study in male Chinese subjects with hemophilia B. The intervention is BeneFIX at 50 IU/kg, and the primary endpoint is maximum observed plasma concentration. The scheduled measurements extend from pre-dose through 96 hours post-dose. These design details establish what the study set out to characterize, but the numerical Cmax result is not reported in the registry record.
The record also reports 0 participants with serious adverse events and 0 participants with other adverse events, each among 12 at risk. Those counts describe the recorded study experience. They do not show that adverse events cannot occur, establish the frequency of rare events, or compare safety with another treatment. Other separately listed safety results are not reported in the registry record.
The findings cannot be interpreted as a treatment-effect estimate because the design lists one group and no comparator. The study does not, in the posted information, establish how Cmax differs from another dose or product. Nor is Cmax itself a clinical outcome: it is a concentration measure. No inference about clinical benefit or lack of benefit follows from the endpoint definition alone.
The enrollment rationale is described as a CFDA requirement for a China pharmacokinetic study and support for registration in China. The registry does not report the primary estimate’s precision, a confidence interval, handling of missing data, or a detailed analysis plan. These omissions prevent a full assessment of uncertainty and reproducibility. The appropriate interpretation is consequently bounded: the record identifies the study design and selected safety counts, while leaving the primary concentration result and several analysis details unreported.
13. Why This Trial Matters Statistically
This study illustrates the distinction between a design record and a complete statistical result. The registry identifies a specific pharmacokinetic target, Cmax, and a sampling schedule extending through 96 hours post-dose. It also identifies the summary scale as a geometric mean with geometric coefficient of variation. Those specifications tell readers what kind of quantity was intended and how its central tendency and spread were to be described, even though the numerical endpoint result is not reported.
It also illustrates why the design determines the scope of an answer. A single-group, open-label study can characterize observations after the listed dose, but it cannot provide a controlled contrast when no comparator is listed. Statistical language should not imply a treatment difference when the design does not estimate one.
The enrollment of 12 is accompanied by a registry statement that it was based on a CFDA requirement for a China pharmacokinetic study and support for registration in China. That administrative and registration context is different from a precision-based sample-size justification. Keeping these rationales separate helps avoid treating a planned enrollment as evidence that a result is precise or adequately powered for a particular comparison.
Finally, the record shows why safety counts require context. Zero affected participants in the listed summary is an observation, not proof that the underlying event risk is zero. The absence of a reported Cmax estimate, confidence interval, and detailed analysis methods also matters: without them, readers cannot judge the primary result’s magnitude, variability or precision. Careful statistical interpretation depends on distinguishing what is registered, what is numerically reported and what remains unreported.
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 for interpreting the primary endpoint is that the registry record does not report the Cmax estimate or its geometric coefficient of variation. It also does not report a confidence interval or the analysis method used to estimate the endpoint. As a result, the magnitude and precision of the primary pharmacokinetic finding cannot be assessed from the posted result information.
The study is listed as single group, open-label and without a comparator. It therefore cannot provide a controlled between-group contrast. Its enrollment was 12, and the population is described as male Chinese subjects with hemophilia B. The findings’ relevance to other populations, settings or dosing approaches is not established by this record.
The intervention is described as a single dose, and the primary endpoint concerns concentration measurements through 96 hours post-dose. The record does not report a longer-term primary endpoint or a clinical outcome analysis. Follow-up procedures beyond the stated pharmacokinetic sampling schedule are not reported in the registry record.
For analysis transparency, the record lists 16 outcome measures but no analysis records. It does not report multiplicity procedures, missing-data handling, treatment of incomplete pharmacokinetic profiles, or a detailed statistical analysis plan. The safety summary reports zero affected participants in its serious and other adverse-event categories, but deaths and separate results for the other listed safety outcomes are not reported. These limitations constrain conclusions to the registered design and the specific reported counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B — NCT02213250.
- Registry record last updated 2016-07-25; status last verified 2016-06.
- Results first posted 2016-07-25.
- 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
NCT02213250 is a completed phase 1, open-label, single-dose pharmacokinetic study sponsored by Pfizer. It enrolled 12 male Chinese subjects with hemophilia B and lists BeneFIX 50 IU/kg as the intervention. The registry states that enrollment was based on a CFDA requirement for a China pharmacokinetic study and support for registration in China.
The primary endpoint is maximum observed plasma concentration, expressed in IU/milliliter (IU/mL), with a geometric mean and geometric coefficient of variation specified. Sampling was scheduled pre-dose and at 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose. The numerical primary result is not reported in the registry record.
The adverse-event summary lists 0 participants affected among 12 at risk for serious events and 0 among 12 at risk for other events. The record lists 16 outcome measures and no analysis records. Detailed analysis methods, missing-data procedures and results for the other listed safety outcomes are not reported in the registry record.