Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis (NCT01340586), a non-randomized phase 1 study. The primary outcome is Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban.

2. Clinical Question

This is a pharmacokinetic question: it concerns the concentration of a drug in plasma over time. The registry describes the study purpose as assessing pharmacokinetics in people with normal renal function and people with end stage renal disease maintained with hemodialysis. It also lists pharmacodynamic outcomes, including changes in coagulation measures and peak anti-FXa activity. Those outcomes are distinct from the primary concentration endpoint.

The record identifies the study as non-randomized, so the groups should not be read as randomized, like-for-like comparison arms. The participant count recorded for enrollment is 18, but the record does not explain how participants were distributed among the described renal-function and dialysis contexts. A precise between-group effect, its uncertainty, and the numerical Cmax values are not reported in the registry record. The study question can therefore be described, but its quantitative answer cannot be reconstructed from the recorded information.

3. Trial Design

This was a phase 1, completed study sponsored by Bristol-Myers Squibb. The recorded start is 2011-06 and the recorded primary completion is 2011-09. The registry lists enrollment as 18. These are registry-level design details; they do not by themselves establish how many participants contributed usable observations to each endpoint.

The design is recorded as non-randomized, unmasked, and parallel. These labels indicate that participants were not assigned by random allocation according to the record, that masking was not used, and that the design model was parallel. The record does not provide enough arm detail to describe the allocation process or the exact comparisons with confidence. Both intervention entries are named apixaban, and the arm descriptions are blank. The study purpose, however, identifies people with normal renal function and people with end stage renal disease maintained with hemodialysis, while the safety listings separately identify dosing before and after hemodialysis.

The intervention is described as a single oral dose of 5 mg apixaban. The primary concentration endpoint covers the period from 24 hours pre-dose to 72 hours post-dose. That timeframe describes when the endpoint was assessed; it does not establish that every participant posted a measurement at every time point. The number and timing of individual blood samples are not reported in the registry record.

Non-randomized allocation matters when interpreting comparisons. General statistical context: random assignment can help balance both measured and unmeasured characteristics across groups, whereas non-randomized groups may differ for reasons other than the study condition. The record does not report an adjustment strategy, and the arm descriptions do not make clear whether a formal comparison was planned between all listed groups. The results should therefore be read as a description of the posted design and outcomes, not as a randomized treatment contrast.

The registry lists 26 outcome measures and 9 analyses. Those counts show that multiple outcomes and analyses were registered, but they do not specify the complete analysis plan, the hierarchy among outcomes, or how all analyses relate to the study groups. Those details are not reported 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: A total of 18 participants were enrolled in this study. 16 participants were treated and completed the study. Two participants were enrolled but not treated (one withdrew consent, one enrolled as alternate).

Overall Study

Analysis population for the primary outcome, as defined in the registry: All treated participants

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 treated participants

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Single 5mg Oral Dose of Apixaban, measured over 24 hours pre-dose to 72 hours post-dose.

The primary endpoint is the geometric mean of maximum observed plasma concentration (Cmax) after a single oral dose of 5 mg apixaban. The record defines Cmax as the maximum observed apixaban plasma concentration over time and gives ng/mL as its unit. The assessment timeframe is 24 hours pre-dose to 72 hours post-dose, and the stated analysis population is all treated participants.

General statistical context: a concentration-time profile describes how the amount of a drug measured in plasma changes after administration. Cmax summarizes the highest observed concentration in that profile. It is used in pharmacokinetic assessment because it represents peak measured exposure, while other features of a concentration-time profile may describe different aspects of exposure. Cmax is not, by itself, a measure of clinical benefit or harm.

The endpoint is expressed as a geometric mean, with geometric coefficient of variation identified as the measure of dispersion. A geometric mean is appropriate for positive measurements that are analyzed on a multiplicative scale; it describes a central value on that scale rather than an arithmetic average. General statistical context: the geometric coefficient of variation conveys relative variability in measurements and is not the same as a standard deviation in the original measurement units.

The registry record does not report the numerical Cmax result, its geometric coefficient of variation, or a group-specific estimate. It also does not report a confidence interval or a formal comparison for this endpoint. Consequently, the endpoint definition can be explained, but the magnitude and precision of the observed concentration cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean describe?

The primary endpoint is reported by type as a geometric mean. General statistical context: when a measurement is positive and variation is naturally considered in proportional rather than additive terms, analysis on a logarithmic scale can be useful. The mean on that transformed scale, when converted back to the original scale, is a geometric mean. This gives a central summary suited to multiplicative variation; it is not an arithmetic mean of the original measurements.

This distinction matters for drug concentrations. A given proportional change has a consistent interpretation across different concentration levels, whereas an equal absolute change can represent very different proportional changes. A geometric summary can therefore be useful for describing concentration data. The record does not state the exact transformation, estimation procedure, or model used to calculate the endpoint, so those implementation details are not reported in the registry record.

How should dispersion be understood?

The listed dispersion measure is the geometric coefficient of variation. General statistical context: a coefficient of variation expresses variability relative to a central scale, rather than in the original unit alone. The geometric version is used with geometric summaries and log-scale variation. It helps describe how spread out the measurements are in relative terms, but it does not identify the shape of the full data distribution or show the precision of a group comparison by itself.

A confidence interval answers a different question. General statistical context: it gives a range of values compatible with the data and the statistical procedure under stated assumptions, and indicates uncertainty in an estimate. A dispersion measure describes variability among observations; a confidence interval describes uncertainty in the estimated quantity. The registry record does not report a confidence interval for the primary endpoint, so precision cannot be judged from the recorded endpoint description alone.

Why do the design labels matter?

The registry classifies allocation as non-randomized and masking as none, with a parallel model. General statistical context: randomization is a method for assigning participants that can reduce systematic differences between comparison groups on average. In a non-randomized study, group membership may be related to participant or clinical characteristics. An unmasked design may also permit knowledge of group status to influence measurement or reporting, depending on the outcome and procedures. These are general considerations, not claims that bias occurred in this study.

The registry does not report a statistical adjustment plan, a prespecified comparison structure, or a detailed account of group assignment. It also gives blank arm descriptions. Because the design details do not fully identify the comparisons, it would be inappropriate to assume that the before-hemodialysis and after-hemodialysis groups represent an independent, randomized contrast, or that they were analyzed in a particular way. The recorded parallel model should be retained as a registry classification rather than expanded into unreported procedural detail.

What is the role of the primary endpoint?

Cmax is the maximum observed plasma concentration during the measurement period. General statistical context: pharmacokinetic endpoints describe drug exposure, whereas clinical endpoints describe outcomes experienced by participants. A peak concentration can answer a question about the highest measured concentration in a sampling profile, but it does not alone describe the entire exposure profile, the duration of exposure, or a participant-centered clinical outcome. The registry lists Cmax as primary and includes coagulation measures and anti-FXa activity as secondary outcomes; it does not report their numerical findings.

The stated analysis population is all treated participants. This identifies the broad population intended for the primary outcome, but the registry does not define treatment, specify which treated participants had an evaluable Cmax measurement, or describe any exclusions from the analysis. The number of participants enrolled is not a substitute for the number contributing to a particular endpoint. Endpoint-specific denominators are not reported in the registry record.

What can the planning illustrations establish?

The registry's sample-size assumptions describe planning illustrations based on the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations consider an effect stated as a fraction of the observed effect. The record also distinguishes between participant counts per arm for most outcomes and total event counts for time-to-event outcomes.

General statistical context: a sample-size illustration asks how many observations a hypothetical future design might require under its assumptions. Such an illustration depends on the assumed effect, variability, allocation, test, and target power. It is not a measure of the probability that the completed study detected an effect, and it is not observed power. Because the primary numerical effect is not reported in the registry record, the illustrations cannot be independently evaluated from the available information. They should not be mistaken for the study's original enrollment rationale or protocol plan.

The record does not report an original sample-size justification, statistical analysis plan, interim analyses, or the methods used to estimate the primary endpoint. General statistical explanations in this discussion clarify the meaning of the endpoint and design labels; they do not establish which procedures the investigators actually used. The registry's stated endpoint type and summary measure are the boundaries of what can be described about the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures and 9 analyses. It names a primary Cmax endpoint and several secondary pharmacodynamic outcomes, including INR, PT, aPTT, and anti-FXa activity. However, the record does not report how the outcomes were organized into a testing hierarchy, whether any outcomes were exploratory, or whether statistical tests were adjusted for multiple comparisons. A multiplicity procedure is not reported in the registry record.

General statistical context: when several hypotheses are tested, the chance of at least one apparently notable result can increase if each test is interpreted separately. Methods for handling multiplicity can include prespecifying a primary test, adjusting significance thresholds, or controlling an error rate across a defined family of tests. Which method is appropriate depends on the design and scientific aim. No such approach can be attributed to this study from the record.

The registry record does not report missing-data counts, reasons for missing observations, imputation methods, or sensitivity analyses. For a concentration endpoint measured over a time window, the availability of observations can affect which participants contribute to an estimate; the record does not describe the sampling completeness or endpoint-specific analysis counts. Missingness should therefore not be assumed absent, and no missing-data mechanism can be inferred.

The primary endpoint population is identified as all treated participants, but further analysis-population definitions are not reported. The record does not explain whether any treated participants were excluded from the primary endpoint analysis or how participants with incomplete measurements were handled. Enrollment, treatment, and endpoint analysis populations should not be treated as interchangeable without those details. The registry gives the study enrollment count, but an endpoint-specific denominator is not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety listings identify three groups: Normal Renal Function, ESRD Dose Before Hemodialysis, and ESRD Dose After Hemodialysis. Each group lists 8 participants at risk for serious adverse events and 8 at risk for other adverse events. The serious adverse event count is 0 in each group. The reported count with other adverse events is 0 for Normal Renal Function, 2 for ESRD Dose Before Hemodialysis, and 1 for ESRD Dose After Hemodialysis.

These are descriptive counts, not comparative estimates. The registry record does not report event terms for serious adverse events, and death counts are not reported in the registry record. It also does not give the event definitions, severity, timing, relationship to apixaban, or whether multiple events could have occurred in one participant. The counts do not establish a causal relationship or support a safety comparison between groups. With no reported inferential analysis or uncertainty interval, the precision of differences in these small listed groups cannot be assessed.

General statistical context: zero recorded events in a group does not prove that an event is impossible or that risk is absent. It means that no events are recorded for that category in the listed group during the reporting period. Interpretation also depends on follow-up duration and completeness, which are not reported in the registry record. The serious and other adverse-event categories should be kept distinct when describing the posted counts.

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

The study record establishes that a single oral dose of 5 mg apixaban was assessed in a phase 1 study involving people with normal renal function and people with end stage renal disease maintained on hemodialysis. It identifies maximum observed plasma concentration as the primary outcome and describes an observation window from 24 hours pre-dose to 72 hours post-dose. The record also identifies pharmacodynamic outcomes and provides group-level adverse-event counts.

Those details define the topic and some aspects of the measurement plan, but they do not provide the primary endpoint result. The numerical Cmax estimate, dispersion, confidence interval, and between-group comparison are not reported in the registry record. The secondary outcome results are also not reported. As a result, the record does not establish the magnitude or precision of apixaban concentrations in the described groups, nor does it quantify how those concentrations compare across renal-function or dialysis contexts.

The posted safety counts offer a limited descriptive account. Serious adverse events are recorded as 0 in each listed group, and other adverse events are recorded in two of the listed end stage renal disease groups. These entries do not characterize the nature, severity, or attribution of events. They cannot establish that a treatment is safe or unsafe, and they do not support a formal comparison among groups.

General statistical context: an observed result, its uncertainty, the design used to obtain it, and the clinical meaning of the measure are separate considerations. Even when a numerical estimate is available, a pharmacokinetic measure such as Cmax is not itself a clinical benefit or harm outcome. In this record, the absence of the numerical result prevents assessment even of the size and precision of the concentration estimate.

The non-randomized design and limited arm descriptions also restrict causal interpretation. Any group difference, if reported elsewhere, could not automatically be attributed to renal function or dialysis timing without understanding allocation, comparability, measurement, and analysis. Those details are not reported in the registry record. The study's completed status and recorded enrollment do not substitute for outcome estimates or resolve these uncertainties.

13. Why This Trial Matters Statistically

This trial is statistically notable because it focuses on pharmacokinetic measurement in two renal-function contexts and records dialysis timing as a distinction in the safety listings. The primary measure, Cmax, concerns peak observed plasma concentration after a single oral dose. Such an endpoint is different from a clinical event or a patient-reported outcome, so its interpretation must remain tied to drug concentration rather than being treated as direct evidence of clinical benefit.

The registry identifies the summary measure as a geometric mean and the dispersion measure as a geometric coefficient of variation. This signals that the endpoint is framed around relative variation in concentration rather than only an arithmetic average. Understanding the scale and dispersion is important when reading pharmacokinetic summaries, because central tendency and variability answer different statistical questions.

The study also illustrates why design details matter. The record classifies allocation as non-randomized and provides blank arm descriptions, while listing three safety groups with different renal-function or dialysis contexts. Those features make it important not to read the groups as a randomized comparison or to assume an unreported analysis strategy. A clear explanation of allocation and endpoint-specific results would be needed for a quantitative comparison.

Finally, the record shows a gap between endpoint registration and result interpretation: it specifies the primary endpoint and timeframe but does not report the numerical Cmax finding. That absence prevents evaluation of the effect's magnitude and precision. The safety counts remain descriptive, and the registered planning assumptions are illustrations rather than evidence of observed power. These distinctions are central to sound statistical reading of a small phase 1 pharmacokinetic record.

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 this trial record is that numerical results for the primary endpoint are not reported. The record names Cmax, its unit, summary measure, dispersion measure, timeframe, and analysis population, but does not give an estimate, confidence interval, or comparison. Numerical results for the listed pharmacodynamic outcomes are also not reported in the registry record.

Design information is incomplete for understanding group comparisons. Allocation is classified as non-randomized, masking as none, and the model as parallel, but the arm descriptions are blank. Both intervention entries name apixaban. The study purpose distinguishes normal renal function from end stage renal disease on hemodialysis, and the safety listings separate dosing before and after hemodialysis, but the record does not fully explain how these contexts map to study arms or how participants were assigned.

The registry does not report endpoint-specific denominators, completeness of concentration sampling, missing-data methods, or analysis exclusions. It also does not report a statistical analysis plan, multiplicity approach, interim analyses, or the study's original sample-size justification. The planning assumptions are described as illustrations based on the observed effect, not as the trial's own design; without the numerical observed effect, their basis cannot be checked from the registry record.

The safety information is limited to counts in the listed categories. Event descriptions, severity, attribution, follow-up duration, and death counts are not reported in the registry record. The counts therefore cannot establish event rates or a comparative safety effect. These limitations constrain both quantitative interpretation and causal claims; they do not imply that unreported analyses or results had any particular value.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetics and Pharmacodynamics of Apixaban in Subjects on Hemodialysis — NCT01340586.
• Registry record last updated 2016-10-11; status last verified 2016-08.
• Results first posted 2016-10-11.
• 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

NCT01340586 is a completed phase 1 study sponsored by Bristol-Myers Squibb. The registry records a start of 2011-06, primary completion in 2011-09, and enrollment of 18. It describes a non-randomized, unmasked, parallel study assessing a single oral dose of 5 mg apixaban in participants with normal renal function and participants with end stage renal disease maintained on hemodialysis.

The primary endpoint is geometric mean maximum observed plasma concentration, measured in ng/mL over 24 hours pre-dose to 72 hours post-dose, with geometric coefficient of variation as the dispersion measure. The primary analysis population is listed as all treated participants. Secondary outcomes include changes in INR, PT, and aPTT, and peak anti-FXa activity. The registry lists 26 outcome measures and 9 analyses.

The numerical primary and secondary results, analysis details, and missing-data methods are not reported in the registry record. Safety listings report 0 serious adverse events in each of three groups and other adverse event counts of 0, 2, and 1, respectively. These are descriptive entries and do not establish comparative effects.