Safety, Pharmacokinetics and Efficacy of an ATIII Concentrate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Pharmacokinetics and Efficacy of an ATIII Concentrate (NCT00319228), a na phase 2, phase 3 study. The primary outcome is Assess the Pharmacokinetic Profile (T1/2) of Anbinex® Using Chromogenic Methods for Subjects Enrolled in Segment 1 of the Study..

2. Clinical Question

The study was intended to assess several aspects of the concentrate in people with congenital deficiency, including pharmacokinetic parameters and safety. Its primary outcome is a measure of drug disposition rather than a direct comparison of clinical outcomes between treatment groups. The registry record also lists area under the curve, mean residence time, volume of distribution at steady state, and clearance among the pharmacokinetic parameters assessed.

That aim should be distinguished from a test of whether the concentrate improves a clinical outcome relative to another option. With a single-group design and no control comparison, changes or observations during the study cannot by themselves establish what would have occurred without treatment. The posted record therefore describes the question and the intended measurements, but it does not give a numerical primary outcome result with which to assess the estimated half-life or its precision.

3. Trial Design

This was a Phase II/III, single-group study of plasma-derived antithrombin III concentrate in congenital antithrombin III deficiency. The registry lists allocation as not applicable and masking as none. Enrollment was 3, and the study status is terminated. Its start date is 2008-04-15, with primary completion listed as 2011-12. The record does not report why the study was terminated.

The study description covers treatment in surgery, pregnancy, and thromboembolic or thrombotic events, while the brief summary states that it assessed safety, pharmacokinetics, and efficacy in subjects with congenital deficiency. The primary outcome specifically concerns the pharmacokinetic profile in Segment 1. The record says that two subjects were in Segment I for the pharmacokinetic description and that no integration across those subjects or statistical analysis of those parameters was performed.

The safety results are divided into Segment I and Segment II. The record lists 2 subjects at risk in each segment for the serious and other adverse-event summaries. These segment-level counts do not align transparently with the overall enrollment of 3; the registry record does not explain the relationship between the segment counts and overall enrollment. They should therefore be read as the reported segment-specific denominators rather than reconciled by assumption.

The registry identifies one intervention, a drug, and a single group named Antithrombin III. There is no randomized comparator arm. The record lists 10 outcome measures and 0 analyses, but does not report numerical results for the primary pharmacokinetic outcome. It also does not report a detailed protocol, reasons for termination, or a sample-size justification. Those omissions limit what can be concluded about the study’s planned comparisons and its statistical execution.

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: In Segment I, 2 subjects were screened for eligibility. Two subjects were enrolled and completed Segment I. Both subjects had at least 1 measurable serum concentration after administration of the investigational product (IP) and thus were eligible for the PK evaluation. Both subjects returned for the Follow-up Visit. Only one Subject from Segment I was included in Segment II. In Segment II, 2 subjects were screened for eligibility. Two subjects were enrolled and completed Segment II

Overall Study

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) population includes all subjects who were enrolled and received at least 1 ATIII-DAF/DI infusion.

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: The intent-to-treat (ITT) population includes all subjects who were enrolled and received at least 1 ATIII-DAF/DI infusion. Segment II includes 1 subject who enrolled in both Segments I and II. Segment II also includes 1 subject who was assigned 2 subject numbers due to 2 clinical events of pregnancy.

6. Primary Endpoint

The registry lists the primary outcome as Assess the Pharmacokinetic Profile (T1/2) of Anbinex® Using Chromogenic Methods for Subjects Enrolled in Segment 1 of the Study., measured over 30 minutes before the first infusion on Day 1 through Day 16 (pharmacokinetic parameters estimated using concentration-time data collected during this period).

The primary outcome is the pharmacokinetic half-life, written as T1/2, of antithrombin assessed using chromogenic methods in subjects enrolled in Segment 1. The registry describes the measurement interval as beginning 30 minutes before the first infusion on Day 1 and continuing through Day 16. Chromogenic assay activity, reported in percent in the study description, was used for pharmacokinetic parameter estimation.

In general, a pharmacokinetic half-life describes how quickly the measured amount or activity of a substance declines over time under a specified model or estimation approach. It is used to characterize drug disposition, not by itself to demonstrate a clinical benefit. The record also names area under the curve, mean residence time, volume of distribution at steady state, and clearance as parameters assessed. These measures describe different features of concentration or activity over time and how the substance is distributed and removed.

The record says the parameters were estimated using noncompartmental analysis of concentration-time data collected from Day 1 through Day 16. It cautions that reported parameter values may be derived estimates and may include extrapolation beyond the last measurable concentration, where applicable. However, it does not report a numerical T1/2 estimate, variability, or confidence interval. The primary outcome’s value and precision therefore cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a pharmacokinetic parameter estimated from measurements collected over time. The registry describes using chromogenic assay activity to estimate pharmacokinetic parameters and noncompartmental analysis to summarize the concentration-time profile. These are methodological descriptions, not numerical findings: the record does not report the primary T1/2 estimate or its uncertainty.

What does T1/2 represent?

In general, T1/2 is a way of expressing the time course of decline in a measured drug concentration or activity. Its meaning depends on the substance, the measurement, and the estimation procedure. A half-life is not a direct measure of clinical benefit, and it does not by itself establish whether a treatment is effective or safe. Here, the outcome title specifies chromogenic methods for antithrombin activity. The record also notes that chromogenic assay data reported in percent were used for estimation.

Pharmacokinetic profiles are built from repeated measurements across time. The recorded interval begins 30 minutes before the first infusion on Day 1 and continues through Day 16. In general, early and later measurements help characterize different parts of the concentration-time profile. The registry does not provide the individual measurements, so it is not possible to inspect their timing, completeness, or pattern.

What is noncompartmental analysis?

In general, noncompartmental analysis estimates pharmacokinetic parameters from observed concentration-time data without requiring a specified compartment model for the body. Parameters named in the registry include T1/2, area under the curve, mean residence time, volume of distribution at steady state, and clearance. Each parameter describes a different aspect of disposition. For example, area under the curve summarizes overall exposure over a period, while clearance describes removal from the measured system. These general definitions explain the type of quantities involved; the registry record does not report their numerical estimates.

The record warns that parameter values are derived estimates based on the concentration-time profile and may include extrapolation beyond the last measurable concentration, where applicable. In general, extrapolation estimates a portion of the profile that was not directly observed, using information from measured data. When an estimate depends partly on extrapolation, interpretation should take that dependence into account. The record does not report whether extrapolation was used for the primary endpoint or how much of any estimate depended on it.

What can a very small pharmacokinetic group show?

The registry states that Segment I included two subjects for the pharmacokinetic assessment and that their data were not integrated. It also states that no statistical analysis of these pharmacokinetic parameters was performed. In general, individual observations can be informative for describing measurements in the participants studied, but a very small group cannot reliably characterize the range of values in a broader population. A formal estimate of variability or uncertainty would require appropriate data and analysis; neither is reported for this outcome.

A confidence interval, in general, expresses a range of values compatible with data and a specified statistical procedure. It communicates uncertainty around an estimate and is not a guarantee that the true value lies in the interval. No confidence interval for T1/2 is reported in the registry record, so its precision cannot be assessed. Similarly, a p-value would address compatibility with a specified statistical hypothesis under assumptions; no such inferential result is reported for the primary pharmacokinetic measure.

How does the design affect inference?

In general, random allocation helps make treatment groups comparable on average and supports a causal comparison when other design and analysis conditions are met. This study has allocation listed as not applicable and is described as single group. It therefore does not provide a randomized treatment contrast. Its pharmacokinetic observations can describe measurements made in the study participants, but do not establish how those measurements compare with an untreated or alternative-treatment group.

Masking is listed as none. In general, masking can reduce the potential for knowledge of treatment assignment to affect measurements, reporting, or assessment. Its absence does not automatically invalidate a measurement, but it is relevant to interpretation, particularly for outcomes involving judgment. The primary outcome is described as laboratory-based activity and pharmacokinetic estimation; the record does not provide further details on laboratory procedures or safeguards.

How should planning illustrations be read?

General sample-size planning asks how many participants would be needed to detect a chosen effect under specified assumptions. The registry’s planning illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence about the design actually used in this single-group study. The record does not report a trial-specific sample-size justification. Any planning number should be understood as an illustration under its assumptions, not as observed power, and not as proof that the trial could or could not detect a clinical effect.

More generally, sample-size calculations depend on the outcome, target effect, variability, allocation, and chosen error rates. Changing an assumption can change the calculated sample size. Where the study does not report a formal plan or sufficient outcome estimates, a planning illustration cannot fill in those missing details. It cannot recover the missing primary result or determine whether the study met a prespecified statistical objective.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 0 analyses. The primary outcome is identified as the pharmacokinetic profile of T1/2 using chromogenic methods, but numerical results for it are not reported. Results for the other outcome measures and any formal analysis of their relationship to the primary outcome are also not reported in the registry record.

When a study assesses multiple outcomes or performs multiple statistical tests, the chance of finding an apparently unusual result can increase if no adjustment or interpretation plan is specified. This is a general statistical concern, not a claim that a particular multiplicity procedure was required or used in this study. A statistical plan addressing outcome hierarchy, repeated testing, or multiplicity is not reported in the registry record. Interim analyses and stopping rules are also not reported.

The registry defines the intent-to-treat population as all enrolled subjects who received at least 1 ATIII-DAF/DI infusion. It does not report whether analyses used this population for the primary pharmacokinetic outcome, how many subjects contributed data to each outcome, or how missing measurements were handled. Missing-data methods, reasons for missingness, and sensitivity analyses are not reported in the registry record.

These omissions matter because the number of participants included in an analysis and the way incomplete observations are addressed can affect estimates and their interpretation. They also prevent assessment of whether the reported outcome population matched a prespecified analysis population. The registry’s statement that pharmacokinetic data from two Segment I subjects were not integrated and that no statistical analysis was performed is the available description of the handling of those parameters; further analytic details are not reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cellulitis (50.0%).

The registry reports safety counts separately for Segment I and Segment II. For serious adverse events, Segment I lists 2 subjects at risk and 1 affected; Segment II lists 2 at risk and 0 affected. For other adverse events, Segment I lists 2 at risk and 2 affected; Segment II lists 2 at risk and 1 affected. Deaths are listed as 0 in both segments. These are the registry’s segment-level figures and should not be added or interpreted as unique-participant totals without clarification, particularly because overall enrollment is listed as 3 while the segment denominators are each 2.

The top listed serious-event term is cellulitis, reported as 50.0%. The registry entry does not provide further context for that percentage, such as an event-level accounting or additional details about timing and attribution. It should therefore be read as a reported term and percentage, not as a causal estimate.

In general, an adverse event is an event recorded during a study; its presence alone does not establish that the intervention caused it. Counts do not describe severity beyond the serious-event classification, duration, recurrence, or comparison with a control group. The registry record does not report a randomized comparator, event narratives, or a causal assessment. The safety figures are descriptive, and the small reported denominators limit how broadly they can be interpreted.

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

The record describes a study intended to assess the safety, pharmacokinetics, and efficacy of plasma-derived antithrombin III concentrate in congenital antithrombin III deficiency. Its primary outcome concerns antithrombin T1/2 estimated using chromogenic methods. The registry gives the measurement period and the general estimation approach, but does not report the numerical primary outcome. The observed half-life and its precision therefore cannot be stated from the registry record.

The study’s single-group design also sets an important boundary on interpretation. It does not provide a randomized control group against which to estimate a treatment difference. Pharmacokinetic estimates, if reported, could describe disposition in the participants measured, but would not alone establish a comparative clinical effect. Similarly, the safety counts describe events recorded in the two segments; they do not establish that the intervention caused or prevented those events.

The registry reports enrollment of 3, while the segment-specific safety summaries each list 2 subjects at risk. It does not explain how those counts relate. The primary pharmacokinetic description refers to two subjects in Segment I. The small number of participants and absence of an integrated pharmacokinetic analysis further limit population-level interpretation. There are no reported confidence intervals or formal statistical analyses with which to quantify uncertainty for the primary outcome.

What the record does establish is the stated study purpose, the intervention, the single-group design, and the planned pharmacokinetic focus. It also reports segment-level adverse-event counts and states that no statistical analysis was performed for the pharmacokinetic parameters. It does not establish a numerical pharmacokinetic result, a comparative treatment effect, or a causal explanation for adverse events. Missing results should not be interpreted as evidence that the intervention had no effect; they indicate that the relevant results are not reported in the registry record.

Planning illustrations based on an observed effect are not observed power and do not substitute for the trial’s own design rationale. Their assumptions describe hypothetical calculations using a two-arm comparison, whereas this study is listed as single group. The registry does not report a study-specific sample-size justification. The illustrations therefore cannot resolve the key interpretive limitations of missing outcome estimates, no control comparison, and limited participant numbers.

13. Why This Trial Matters Statistically

This study illustrates why a registry’s design description and its posted results must be considered together. The stated primary aim is pharmacokinetic: to assess antithrombin T1/2 using chromogenic methods over a defined measurement period. The record identifies the estimation approach and related pharmacokinetic parameters, but gives no numerical primary result. Without an estimate, a reader cannot assess the observed magnitude or its precision, regardless of the clinical interest of the question.

It also demonstrates the difference between describing a pharmacokinetic profile and testing a comparative clinical effect. A single-group study can provide observations about participants who received an intervention, but a randomized control group is needed for a direct randomized comparison. The registry lists no allocation and no masking, and it does not identify a control arm. Conclusions should remain within the descriptive scope of the record.

The very small counts are also consequential. The pharmacokinetic description concerns two Segment I subjects, and the registry explicitly says their data were not integrated and no statistical analysis of those parameters was performed. The overall enrollment of 3 does not reconcile transparently with safety denominators of 2 in each segment. This emphasizes the need to understand analysis populations and participant flow before treating counts as a coherent total.

Finally, the record underscores that planning illustrations are not equivalent to a study’s prespecified sample-size rationale. Calculations based on two-arm assumptions do not describe the design of a single-group study. A registry record is most informative when it reports the planned analysis, the population analyzed, missing-data handling, and numerical estimates with uncertainty. Those details are not reported for the primary outcome here, so the statistical question remains unresolved in the posted 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 principal limitation is that the registry record does not report the numerical primary outcome. Although it identifies T1/2, the chromogenic method, and the data-collection interval, it provides no estimate, measure of variability, or confidence interval. The reader cannot assess the size or precision of the pharmacokinetic result.

The primary pharmacokinetic description concerns two subjects in Segment I. The record says that data were not integrated across those subjects and that no statistical analysis of the parameters was performed. This precludes an inferential summary of the primary measure. The registry also does not report individual concentration-time measurements, so data completeness and the shape of the observed profile cannot be examined.

The overall enrollment is listed as 3, but safety summaries give 2 subjects at risk in each of Segment I and Segment II. The registry record does not explain the relationship between these figures or whether the segment counts represent distinct participants. No assumptions should be made to reconcile them.

The single-group design has no randomized comparator, and masking is listed as none. Consequently, the study does not estimate a randomized treatment contrast. The registry does not report a detailed statistical analysis plan, missing-data methods, interim analyses, stopping rules, or the reason for termination. It also does not provide a trial-specific sample-size justification. These limitations leave important questions about the intended analyses and the interpretation of incomplete or absent results unanswered.

The reported safety counts are small and descriptive. The registry does not provide detailed event narratives or a causal assessment, and its top serious-event term is listed without further context. These records cannot establish whether an adverse event was caused by the intervention or how risks compare with another treatment or control.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Pharmacokinetics and Efficacy of an ATIII Concentrate — NCT00319228.
• Registry record last updated 2026-10-07; status last verified 2026-09.
• Results first posted 2026-10-07.
• 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

This terminated Phase II/III study assessed plasma-derived antithrombin III concentrate in people with congenital antithrombin III deficiency. It is listed as a single-group study with no masking, enrollment of 3, and no randomized allocation. The start date is 2008-04-15 and primary completion is listed as 2011-12.

The primary outcome concerns antithrombin T1/2 measured using chromogenic methods in Segment 1, with pharmacokinetic data collected from 30 minutes before the first infusion on Day 1 through Day 16. The record describes noncompartmental estimation and lists related pharmacokinetic parameters, but no numerical primary result or statistical analysis is reported.

Safety counts are reported by Segment I and Segment II, with 0 deaths listed in each. The record does not reconcile those segment denominators with overall enrollment. A trial-specific sample-size justification, detailed analysis plan, missing-data approach, and reason for termination are not reported in the registry record.