A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions (NCT02081950), a na phase 1 study. The primary outcome is Anti-FXa Cmax.

2. Clinical Question

The question is about how Anti-FXa measurements vary within the same participant across the study periods, rather than about a treatment effect against a separate control. Repeated measurements in a participant can be used to describe within-subject variation, but the registry record does not give the numerical period-specific results or the statistical procedure used to quantify that variation. It therefore does not support a numerical estimate of how consistent the measurements were.

The registry also states a secondary objective of monitoring safety during the treatment periods. It lists secondary pharmacokinetic outcomes for Anti-FXa and Anti-FIIa, including timing, half-life, and minimum concentration measures. The existence of these outcomes does not establish that their numerical results are available. Those results, along with the primary endpoint result, are not reported in the registry record.

3. Trial Design

This was a completed Phase 1, single-group study sponsored by Chemi S.p.A. The registry record gives a start date and primary completion date of 2014-03 and lists enrollment of 14. It describes healthy adult volunteers receiving enoxaparin sodium as a single subcutaneous dose under fasting conditions. The planned administration is described as occurring in 2 periods.

Allocation is recorded as NA, masking as none, and the study model as single group. Thus, the record does not describe random assignment to separate treatment and control arms, nor does it describe masking. The study periods should not be treated as independent, randomized groups: the primary objective explicitly concerns within-subject variability, and the intervention description refers to administration in both periods. The record does not report the order of period treatments or other details that would establish a specific sequence or washout procedure.

The primary endpoint was Anti-FXa Cmax, with units of IU/mL. Measurements were scheduled before dosing and at the listed post-dose times in Period 1 and Period 2. The registry identifies the reported summary type as a mean with standard deviation. Those endpoint summaries are not reported in the registry record, so the planned schedule and summary type do not reveal the observed values or the amount of within-subject variability.

The record lists 34 outcome measures and 14 analyses. It does not report a detailed statistical analysis plan, sample-size justification, handling of missing measurements, or method for assessing within-subject variability. A planning illustration is described using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. Those assumptions do not describe the study’s single-group, repeated-period design, and no planning outputs are available in the registry record to interpret.

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: This is a single arm study and not a parallel group study. This means that the participants are 14 in total. The 14 eligible subjects received 1 dose of s.c. Clexane in Treatment Period 1 and 1 dose of S.C. Clexane in Treatment Period 2 (1 dose/period). Each Treatment Period was of 2 days duration.

Treatment Period 1

Treatment Period 2

Analysis population for the primary outcome, as defined in the registry: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.

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 subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.

6. Primary Endpoint

The registry lists the primary outcome as Anti-FXa Cmax, measured over Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2..

The primary endpoint, Anti-FXa Cmax, is the maximum measured Anti-FXa value in the post-dose profile. It is reported in IU/mL. The registry describes Cmax as the maximum or peak concentration in a specified compartment or test area after administration and before another dose. In this study, the measure is based on anti-Factor Xa activity rather than a direct measurement of enoxaparin in blood.

The registry explains that enoxaparin’s anticoagulant effect is assessed through its effects on clotting mechanisms, particularly inhibition of activated factor Xa and factor IIa. Enoxaparin cannot be measured directly in blood according to the record, so Anti-FXa and Anti-FIIa activity are used as pharmacokinetic measures. Cmax therefore summarizes the peak Anti-FXa measurement in a profile; it is not itself a direct assay of the amount of enoxaparin present.

For a study focused on within-subject variability, repeated profiles can be compared within participants to characterize how peak measurements vary across periods. That is a general statistical rationale for repeated-period measurements, not a statement about the procedure used in this study. The registry specifies that the endpoint was summarized as a mean and standard deviation, but does not report the observed mean, standard deviation, or a numerical estimate of within-subject variability. The magnitude and precision of the endpoint result therefore cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary question concerns within-subject variability. In general, within-subject variability describes how repeated measurements from the same person differ under the conditions being studied. It is distinct from variation between people: participants can have different average levels while each person’s repeated measurements are relatively consistent, or the reverse. Repeated measurements can help separate these sources of variation when the design and analysis account for their dependence.

Here, the registry describes one group and treatment administration in 2 periods. That structure differs from a parallel-group trial in which separate participants are assigned to different treatments. Measurements from the same person across periods are related, so an analysis ordinarily needs to preserve the pairing or otherwise model the repeated observations. Treating period observations as unrelated would discard information about the within-person relationship. This is a general methodological point; the registry record does not specify which procedure was used.

The primary endpoint is Anti-FXa Cmax, expressed in IU/mL, and the listed summary is a mean with standard deviation. A mean gives a central summary of measurements, and a standard deviation expresses how spread out the measurements are around that mean. Neither statistic alone necessarily describes within-subject variability in a repeated-period design. To interpret such variability, the analysis must clarify whether the dispersion reflects participant-to-participant differences, within-person differences across periods, or a combination. The registry record does not supply that clarification or the numerical summaries.

Anti-FXa Cmax is a peak measure from a concentration- or activity-time profile. Measurements were planned before dosing and at the stated post-dose times in Period 1 and Period 2. The timing schedule matters because the maximum observed value depends on when samples are collected; a peak between scheduled measurements may not be directly observed. This is a general feature of sampled profiles, not evidence that the study missed its peak. The registry record does not report the individual profiles or the observed time of maximum activity.

The registry’s description distinguishes enoxaparin from its pharmacodynamic measurement. It states that enoxaparin cannot be measured directly in blood and that pharmacokinetic assessments were based on its effects on clotting mechanisms, particularly Anti-FXa and Anti-FIIa activity. The primary endpoint should therefore be understood as an Anti-FXa measure used to characterize the drug’s profile, not as a direct blood concentration of enoxaparin. The record does not provide assay-performance information or details about how measurements were processed.

A confidence interval, in general, communicates the uncertainty associated with an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but precision is not the same as absence of bias or clinical importance. No confidence interval for Anti-FXa Cmax or within-subject variability is reported in the registry record. There is therefore no interval-based assessment of precision to discuss.

Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. If a model understates variability, standard errors and confidence intervals can be too small, making results appear more precise than they are. This concept is relevant to repeated measurements in general, but the registry record does not report a model, a dispersion assessment, or evidence of over-dispersion. It would be inappropriate to claim that this issue occurred in this study.

Missing measurements can also affect profile summaries. In general, if measurements are unavailable at some scheduled times, the resulting endpoint may depend on how missing values and incomplete profiles are handled. The registry defines a PK analysis population using receipt of study medication in both periods, sufficient plasma activity or concentration-time profiles, and absence of major protocol violations that could invalidate or bias results. It does not report the number included in that analysis or explain how incomplete data were treated. Whether any participants or measurements were excluded, and the consequences of any exclusions, are not reported in the registry record.

The registry lists 34 outcome measures and 14 analyses. Multiple outcomes can create multiplicity concerns when many hypotheses are tested, because the chance of at least one apparently noteworthy result can increase across tests. A prespecified hierarchy or adjustment can address that concern, but the analysis plan and any multiplicity procedure are not reported in the registry record. The number of listed measures and analyses does not reveal how many statistical tests were performed or which conclusions were treated as confirmatory.

The record also gives assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and target effects described as fractions of the observed effect. Those are planning assumptions, not a report of the study’s observed power. They do not align directly with the described single-group, repeated-period design, and the registry record does not provide the resulting planning values. Such illustrations should not be read as evidence that the study had a particular probability of detecting an effect.

Finally, a statistical analysis plan would ordinarily clarify the estimand, handling of period effects, model structure, treatment of missing data, and the method for estimating within-subject variation. The registry record does not report these details. The available design and endpoint descriptions support a general explanation of the intended question, but they are not enough to reproduce the analysis or verify the statistical methods used.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Treatment Period 1", "Treatment Period 2")
n   <- c(14, 14)
m   <- c(0.999, 0.926)
sp  <- c(0.255, 0.204)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Treatment Period 1  14  0.999  0.255  0.852  1.146
CARM  Treatment Period 2  14  0.926  0.204  0.808  1.044

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 34 outcome measures and 14 analyses, including the primary Anti-FXa Cmax endpoint and secondary Anti-FXa and Anti-FIIa measures. Having multiple outcomes can raise multiplicity concerns if statistical tests are used to support multiple claims. In general, multiplicity procedures may control the overall false-positive risk or define an order of testing. The registry record does not report whether any adjustment, testing hierarchy, or other multiplicity strategy was used. The number of listed measures and analyses does not by itself establish how many hypotheses were tested or which were considered primary for inference.

The record identifies a PK analysis population: participants who received study medication in both treatment periods, had sufficient plasma activity or concentration-time profiles, and did not have major protocol violations judged capable of invalidating or biasing results. It does not report how many participants met those criteria, how many were excluded, or whether the posted safety counts use the same population. The registry record also does not describe an intention-to-treat population or another analysis population.

Methods for missing observations are not reported in the registry record. In particular, it does not explain how incomplete profiles, missing scheduled measurements, or unavailable endpoint values were handled. There is no report of imputation, sensitivity analyses, or reasons for missingness. These omissions matter because profile-based endpoints and repeated-period comparisons can be affected by which observations are available.

The registry’s planning assumptions do not fill these gaps. A sample-size illustration is not a substitute for the analysis plan, and its two-arm assumptions do not match the recorded single-group design. The registry record does not report a formal multiplicity plan, missing-data strategy, or complete analysis-population results.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports safety counts separately for Treatment Period 1 and Treatment Period 2. For each period, it lists 14 participants at risk for serious adverse events and 0 affected. It lists 14 at risk for other adverse events, with 4 affected in Treatment Period 1 and 2 affected in Treatment Period 2. No deaths are listed in either period.

These are period-specific counts. Because the study is single-group and uses repeated treatment periods, the period rows should not be read as independent comparison arms or added together to describe unique participants. The registry does not report whether the same participants experienced events in both periods, nor does it provide event terms for the other adverse events. Serious-event counts and other-event counts are distinct categories in the record; the absence of listed serious events does not mean that no other adverse events were recorded.

The counts do not describe event severity beyond the serious-event classification, timing, duration, or the investigators’ assessment of relationship to treatment. The registry record does not report those details. These figures are descriptive and do not establish a comparative safety effect.

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

The record documents a Phase 1 study designed to examine within-subject variability of Anti-FXa Cmax after a single subcutaneous dose of enoxaparin sodium under fasting conditions. It specifies the endpoint, measurement schedule, summary type, treatment-period structure, and a PK analysis population definition. It also reports selected safety counts by period.

What the record does not show is the numerical result for the primary endpoint. No mean, standard deviation, confidence interval, or estimate of within-subject variability is reported. Consequently, it is not possible to say how large the observed variation was or how precisely it was estimated. A design objective is not an observed result, and the endpoint’s definition does not establish the outcome.

The single-group structure also limits what can be inferred. There is no separate control group described, and the two periods are not presented as randomized arms. Period-specific observations may be relevant to the within-subject question, but a valid interpretation requires the analysis method and numerical results, which are not reported in the registry record. The study therefore does not provide a posted treatment-versus-control estimate.

General statistical interpretation distinguishes measurement variability from treatment benefit or harm. Anti-FXa Cmax is a biomarker-based measure used to characterize the profile described in the registry; it is not itself a clinical outcome. The registry’s safety counts are likewise descriptive and lack event-level detail and comparative analysis. They should not be translated into a broader claim about safety.

The record also does not report a statistical analysis plan, missing-data approach, confidence intervals, or multiplicity procedure. Those omissions prevent assessment of model assumptions, analytic robustness, and the precision of any estimate. The posted information can establish what the study set out to measure and how the registry characterizes its design, but it cannot support conclusions about the observed degree of variability or clinical implications.

14. Why This Trial Matters Statistically

This study is statistically notable because its question concerns repeated measurements within the same participant rather than a contrast between separate randomized groups. That distinction changes what a useful summary must capture. Between-person differences and within-person variation are not interchangeable, and an analysis needs to account for the repeated-period structure to answer the stated question clearly.

The endpoint also illustrates a common issue in clinical pharmacology: a drug may be characterized through a measured biological activity rather than by a direct measurement of the drug itself. The registry describes Anti-FXa activity as the basis for assessing the enoxaparin profile and identifies the peak measure as the primary endpoint. Interpretation therefore depends on distinguishing the biological measurement from a direct concentration of the administered compound.

The registry record demonstrates why endpoint definitions and analysis details need to be read separately. It specifies Anti-FXa Cmax, its units, measurement times, and a mean-and-standard-deviation summary, but it does not report the numerical endpoint results or the method used to quantify within-subject variation. A clear endpoint description is useful, yet it cannot substitute for results or an analysis plan.

The design is also a reminder that repeated treatment periods are not equivalent to independent arms. Period-specific safety counts do not automatically form a comparative analysis, and repeated observations may be linked within participants. The record’s planning assumptions for two-arm sample-size illustrations are not directly aligned with the stated single-group design, making it important to distinguish a planning calculation from the study’s actual design and findings.

Finally, the registry lists multiple outcomes and analyses without reporting a multiplicity strategy, missing-data methods, or complete analysis-population results. These are important elements for evaluating the reliability and precision of findings. In this record, their absence limits statistical interpretation even though the objective and primary endpoint are clearly identified.

15. 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 interpretation is that the registry record does not report numerical results for the primary endpoint. Without the observed Anti-FXa Cmax summaries or a direct estimate of within-subject variability, the stated primary objective cannot be evaluated from the posted record. Precision cannot be assessed because no confidence interval or comparable uncertainty measure is reported.

The population was described as healthy male and female volunteers under fasting conditions. Findings from such a study, even if numerical results were available, would not automatically characterize other populations or conditions. The registry record does not give details about participant characteristics beyond the healthy-adult description, so subgroup interpretation is not available.

The intervention was a single subcutaneous dose of enoxaparin sodium in 2 periods. This record does not describe a separate control group, random allocation, or masking. It therefore does not support a randomized treatment comparison. The registry also does not report the order of period administration, washout details, or an analysis of possible period effects.

The analysis information is incomplete. The record defines a PK population but does not state its analyzed size or provide a complete accounting of exclusions. It does not report missing-data methods, the statistical model for repeated observations, an analysis plan, or a multiplicity procedure despite listing 34 outcome measures and 14 analyses. Without those details, the analysis cannot be reproduced or assessed for robustness.

Safety information is limited to period-specific counts. The record does not list the terms of the other adverse events or provide severity, timing, attribution, or participant-level overlap across periods. The counts should therefore be read descriptively, not as a full safety profile or comparative estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions — NCT02081950.
• Registry record last updated 2020-11-12; status last verified 2020-10.
• Results first posted 2020-09-29.
• 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.

19. Record Summary

NCT02081950 is a completed Phase 1, single-group study sponsored by Chemi S.p.A. It enrolled 14 healthy adults and examined a single 80 mg subcutaneous dose of enoxaparin sodium under fasting conditions in 2 treatment periods. Allocation is recorded as NA and masking as none.

The primary endpoint was Anti-FXa Cmax in IU/mL, summarized as a mean with standard deviation. The primary objective was to examine within-subject variability. The registry record does not report numerical results for that endpoint, an estimate of variability, or its precision. It lists 34 outcome measures and 14 analyses, but does not report a detailed statistical analysis plan, multiplicity strategy, or missing-data methods.

Safety counts are reported by treatment period: no serious adverse events or deaths are listed, while other adverse events are recorded in both periods. The registry does not provide event-level details or a comparative safety analysis. The record describes the study question and design, but its posted results do not permit a numerical interpretation of the primary endpoint.