A Study to Characterize the PK and PD Profile of IV FCM in Pediatric Subjects 1-17 Years Old With IDA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Characterize the PK and PD Profile of IV FCM in Pediatric Subjects 1-17 Years Old With IDA (NCT02410213), a na phase 2 study. The primary outcome is Maximum Serum Concentration (Cmax).

2. Clinical Question

The study’s stated purpose was to characterize pharmacokinetic and pharmacodynamic profiles after FCM dosing. Its primary outcome focuses specifically on the maximum serum concentration observed over the concentration-time profile. That is a descriptive pharmacokinetic question: it concerns drug concentration in serum over time, rather than a randomized comparison of clinical outcomes.

The registry describes two dose cohorts, but does not identify a randomized assignment process or a control condition. Therefore, a contrast between cohort results, if presented elsewhere, would not by itself establish that dose caused any difference. The cohorts were not assigned through a randomized comparison, and the registry record does not report an adjusted analysis that addresses potential differences between them.

The primary question should also be kept distinct from the broader PK/PD characterization aim. The outcome record identifies Cmax, while other pharmacokinetic or pharmacodynamic endpoints and their results are not reported in the registry record. The registered question is thus about measured serum concentration, not a documented estimate of comparative clinical benefit.

3. Trial Design

This was a Phase II, open-label, non-randomized, multi-center, single-arm study of intravenous ferric carboxymaltose in pediatric subjects with iron deficiency anemia. The registry classifies its model as sequential and records enrollment of 35. Its status is completed. The registry record gives no details about how sites were selected or how participants entered the dose cohorts.

The study included Cohort 1, receiving FCM at 7.5 mg/kg, and Cohort 2, receiving FCM at 15 mg/kg. For either cohort, the dose was capped at a maximum single dose of 750 mg iron, whichever was smaller. The registry describes both cohorts as receiving the same intervention at different dose levels. It does not report random assignment, masking, or a parallel control group; the study is explicitly open-label and non-randomized.

These design features matter for interpretation. An open-label study does not conceal the intervention from participants or study personnel, and a non-randomized cohort structure does not ensure that the groups are comparable in all other respects. The registry record does not report baseline characteristics by cohort, so the extent of any cohort differences cannot be assessed from this information. The sequential model is recorded, but the protocol for sequencing cohorts is not reported in the registry record.

The outcome record identifies a continuous primary measure: maximum serum concentration, or Cmax, in µg/mL. The measure was to be obtained from the serum concentration-time profile, with sampling specified prior to dosing and at 1, 2, 6, 12, 48 and 72 hours post dosing. This schedule describes the planned measurement times, not the completeness of the resulting data. The registry record does not report the observed Cmax results, cohort-specific estimates, or a formal comparison between doses.

The registry identifies American Regent, Inc. as sponsor. It records the study start as 2015-02-19 and primary completion as 2017-01-22. These dates describe the registered study timeline; they do not provide information about recruitment pace, protocol changes, or the timing of analyses, none of which is 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: In Cohort 1, pharmacokinetic parameter values are excluded for one subject due to anomalous and consistently high concentrations, and for one subject due to missing concentration data at 1 and 2 hours post-dose.

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.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Serum Concentration (Cmax), measured over prior to dosing and 1, 2, 6, 12, 48 and 72 hours post dosing.

The primary endpoint is maximum serum concentration (Cmax), measured in µg/mL. The registry defines it as the maximum observed serum concentration obtained directly from the serum concentration-time profile. This is a pharmacokinetic measure: it describes the highest measured concentration in serum over the specified observation period, rather than a clinical symptom or a measure of treatment benefit.

The concentration-time profile includes measurements prior to dosing and at 1, 2, 6, 12, 48 and 72 hours post dosing. Cmax is useful in pharmacokinetic characterization because it condenses the concentration profile into a measure of peak observed exposure. The peak may be of interest when describing how concentration changes after administration. As a general statistical point, however, Cmax alone does not describe the full time course, total exposure, or clinical consequences of a drug concentration.

The registered summary measure is the mean, with standard deviation as the dispersion measure. A mean describes the central value of observations; the standard deviation describes their spread around that mean. These are descriptive summaries, not a test of whether the dose cohorts differ. The registry record does not report the observed mean Cmax, its standard deviation, confidence intervals, or a dose comparison. It therefore does not permit a numerical interpretation of the endpoint’s magnitude or precision.

For Cohort 1, the registry notes that pharmacokinetic parameter values were excluded for one subject because of anomalous and consistently high concentrations, and for one subject because concentration data at 1 and 2 hours post-dose were missing. This note is specific to the Cohort 1 PK parameters; the record does not give a fuller account of endpoint availability by cohort.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is continuous, and the registry specifies a mean and standard deviation. In general, the mean is a summary of the center of measured values. The standard deviation describes how dispersed individual values are around that center. Together they give a basic description of a distribution, but they do not show its full shape. If observations are skewed or include unusual values, the mean and standard deviation can be influenced by those features. The registry record does not describe the distribution of Cmax or report any observed summary values.

The standard deviation should not be mistaken for the standard error or for a confidence interval. As a general distinction, the standard deviation describes variation among observations, while the standard error describes uncertainty in an estimated statistic. A confidence interval uses an estimate and its uncertainty to express a range compatible with the data under a specified procedure. No standard error, confidence interval, or inferential procedure for Cmax is reported in the registry record.

How is Cmax obtained?

The endpoint is the maximum observed serum concentration taken from a concentration-time profile. The record specifies measurements prior to dosing and at 1, 2, 6, 12, 48 and 72 hours post dosing. In general, measuring concentration at multiple times makes it possible to describe how concentrations change after administration. The observed maximum is the largest value among the measured concentrations included in the profile. It depends on the measurements that are available and on when they were collected; it is not automatically a direct observation of every moment between scheduled measurements.

The record identifies the endpoint as the maximum observed concentration, but does not report how any incomplete profiles were handled beyond the Cohort 1 exclusions described for PK parameter values. It does not state whether Cmax was calculated from a particular analysis population, whether values were transformed, or whether the mean and standard deviation were calculated on the original scale. Those methodological details are not reported in the registry record.

What can a cohort contrast establish?

In general, a randomized comparison uses an assignment process intended to make treatment groups comparable, on average, apart from the intervention. This study is listed as non-randomized and single-arm, with sequential cohorts receiving different dose levels. Thus, cohort summaries can describe the observed results for each cohort, but a difference between them would not automatically be attributable to dose. Potential differences in participant characteristics, study conduct, timing, or other factors could also contribute. The registry record does not report baseline comparisons or an adjusted model that addresses such factors.

The study is open-label, so masking is listed as none. For an objectively measured serum concentration, lack of masking may have a different direct influence than it would for a subjective outcome, but it does not resolve the limitations of non-randomized allocation. It also does not establish that measurements, exclusions, or data handling were free from influence. The registry record does not describe quality-control procedures, assay methods, or blinded assessment.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when variability in the data is greater than a model assumes. A model that understates variation can make uncertainty appear smaller than it is, affecting standard errors, confidence intervals, or tests. It can be relevant when outcomes vary substantially across participants or when a statistical model imposes a restrictive variance structure. The registry record does not identify an over-dispersion assessment or a model for the primary endpoint. Because the listed endpoint is continuous and summarized by a mean and standard deviation, the record alone does not establish whether over-dispersion is relevant to the actual analysis.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, rather than the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event illustrations, the record says the result is a total number of events using the Schoenfeld method; other illustrations are expressed as participants per arm.

These are planning assumptions, not evidence about the trial’s actual power or its results. A sample-size calculation asks what study size would be needed under chosen assumptions. It does not show the probability that this completed study detected an effect, and it does not replace an analysis of observed data. The registry record does not report a sample-size justification for the original study, its planned power, or a protocol-based sample-size calculation. Any planning illustration based on an observed effect should be interpreted as conditional on that effect estimate and the stated assumptions, not as an observed trial outcome.

The registry record lists 0 analyses and does not report a p-value, confidence interval, model, or test for the primary endpoint. Therefore, there is no basis in the registry information for describing a statistically significant or non-significant result. A lack of a reported test is not evidence that the endpoint had no variation or that a comparison was negative; the inferential result is simply not reported in the registry record.

What does multiplicity mean for this study?

In general, multiplicity arises when several outcomes, time points, subgroups, or comparisons are tested, increasing the chance of at least one apparently unusual finding if each test is treated independently at a conventional threshold. The concentration-time profile includes multiple scheduled measurements, while the listed primary endpoint is the maximum observed concentration. The registry record does not explain whether any additional endpoints or comparisons were tested, how the maximum was defined for incomplete profiles, or whether multiplicity was addressed. A multiplicity adjustment should not be assumed.

The absence of these details limits interpretation of any results found outside the registry record. Without a defined analysis plan, it is not possible to distinguish confirmatory analyses from exploratory descriptions or to know how the choice of outcomes and comparisons was handled. This is a general limitation of incomplete reporting, not evidence that a particular analysis was inappropriate.

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("Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg", "Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg")
n   <- c(14, 19)
m   <- c(157, 310)
sp  <- c(33.8, 13.9)
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  Cohort 1: Ferric Carboxymaltose (FCM) 7.5 mg  14  157.000  33.800  137.484  176.516
CARM  Cohort 2: Ferric Carboxymaltose (FCM) 15 mg/kg  19  310.000  13.900  303.300  316.700

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies Cmax as the primary outcome and gives its measurement schedule, but does not report an analysis plan for the endpoint. The record lists 0 analyses. It does not report whether additional pharmacokinetic or pharmacodynamic outcomes were analyzed, whether results were tested at multiple time points, or whether any multiplicity procedure was used. In general, multiplicity can arise when multiple outcomes or comparisons are examined; without a stated plan, the protection against selectively emphasizing results cannot be evaluated. A correction or adjustment should not be inferred.

The record does report a specific PK exclusion note for Cohort 1. PK parameter values were excluded for one subject because concentrations were anomalous and consistently high, and for one subject because concentration data at 1 and 2 hours post-dose were missing. The note does not provide the decision rules used to classify the concentrations as anomalous, identify who made the decision, or state whether sensitivity analyses included those values. Those details are not reported in the registry record.

The record does not describe the amount or pattern of missingness in the remaining data, how missing measurements were handled in calculating Cmax, or whether missingness differed by cohort. It also does not define the complete analysis populations for the primary outcome. The two specified exclusions should therefore be understood as the exclusions explicitly noted for Cohort 1 PK parameters, not as a complete account of all data availability or exclusions.

In general, missing-data handling can affect which observations contribute to a summary and how representative that summary is of the intended population. Excluding observations can be appropriate under a prespecified rule, but interpretation depends on the rationale, consistency of application, and impact of the decision. The registry record does not report these broader details, so the robustness of the endpoint results to missing or excluded data cannot be assessed from it.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sinusitis (6.2%), upper respiratory tract infection (6.2%).

The registry reports serious adverse event counts by dose cohort. In Cohort 1, 2 participants were affected among 16 at risk; in Cohort 2, 0 were affected among 19 at risk. It reports 0 deaths in each cohort. The record also lists other adverse events for 9 among 16 at risk in Cohort 1 and 12 among 19 at risk in Cohort 2. These are the recorded counts; they should not be read as a randomized comparison of safety.

The serious adverse event terms listed include Sinusitis and Upper Respiratory Tract Infection, each reported at 6.2%. The record does not give cohort attribution for those terms in the information available, so they should not be assigned to a particular cohort. Nor does the record explain whether the listed terms account for all serious events or how event counts relate to participants affected.

In general, safety counts describe events recorded during a study and depend on definitions, observation, and reporting. The registry record does not provide event timing, duration, severity details beyond the serious-event classification, causal attribution, or a statistical comparison. The small, non-randomized cohort structure also means the observed counts cannot establish that one dose causes more or fewer events than another. No medical conclusion should be drawn from these counts alone.

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

The study’s registered purpose was to characterize the PK/PD profile of intravenous FCM in pediatric subjects with IDA. Its primary endpoint, Cmax, describes the maximum observed serum concentration. The registry record reports the endpoint definition, the concentration-measurement schedule, and a mean-with-standard-deviation summary plan. It does not report the observed Cmax values, uncertainty estimates, or a formal analysis. Thus, the record describes what was to be measured but does not provide the numerical primary result.

The study enrolled participants into sequential dose cohorts, with FCM at 7.5 mg/kg or 15 mg/kg up to a maximum single dose of 750 mg iron, whichever was smaller. Because allocation was non-randomized and the study was open-label and single-arm, the cohorts do not constitute a randomized control comparison. Descriptive cohort results, if available in another source, would not by themselves establish a causal dose effect.

The record’s safety counts report serious adverse events, other adverse events, and deaths by cohort. These are useful descriptions of events recorded during the study, but the information reported does not establish comparative safety or causal attribution. The serious terms listed with 6.2% are not assigned to a cohort in the record information available. The stated exclusions for Cohort 1 PK parameter values also mean that at least some observations were not included for the reasons recorded; the effect of those exclusions is not reported.

In general, pharmacokinetic measures describe drug concentration, while clinical outcomes concern how participants feel, function, or experience health events. A serum concentration measure is not, on its own, proof of a clinical benefit or harm. This registry record does not report a clinical efficacy endpoint result or a completed statistical analysis of Cmax. It therefore cannot establish whether FCM works or does not work, nor can it establish a comparative clinical effect between dose cohorts.

The appropriate reading is narrow: the registry documents a completed Phase II PK/PD study, its dose cohorts, primary concentration measure, and selected safety counts. Interpretation of the magnitude and precision of Cmax, the completeness of analysis, and any dose-related difference requires results and methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between describing an intended measurement and reporting an analyzed result. The registry defines Cmax as the maximum observed concentration from a specified serum profile and names the mean and standard deviation as summaries. Those details help identify the estimand-like target of the primary outcome, but they are not substitutes for the actual estimate, its uncertainty, or an analysis. Since those results are not reported in the registry record, the central statistical question remains unanswered in the registered information.

The design also makes clear why comparisons require care. The record describes sequential, non-randomized cohorts at different dose levels, rather than a randomized control comparison. A difference between cohort summaries could reflect dose, but it could also reflect cohort composition or other factors. Statistical adjustment may address measured differences under suitable assumptions, but an adjustment is not reported in the registry record, and statistical methods cannot guarantee removal of unmeasured differences.

The PK exclusion note is important because a mean and standard deviation summarize the observations that enter the calculation. Excluding values for anomalous concentrations or missing early measurements may alter the analyzed set and the resulting summary. That does not establish whether the decision was right or wrong; it points to the need for transparent rules and sensitivity analyses when interpreting a concentration endpoint. Such details are not reported in the registry record.

The record also provides a useful distinction between trial planning and trial evidence. It describes a sample-size planning framework that uses an observed effect and specified statistical assumptions. In general, a planning illustration is conditional on its assumptions and is not “observed power.” It cannot establish how informative this completed study was without the observed estimate and its precision. The original trial’s sample-size justification and planned analysis are not reported in the registry record.

These features matter for readers evaluating registry evidence: endpoint definition, allocation method, data exclusions, analysis reporting, and uncertainty all shape what a result can support. Here, the registry information permits a description of the design and selected event counts, but not an assessment of the primary concentration estimate or its statistical precision.

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 main limitation for interpreting the registered outcome is that the primary Cmax results are not reported in the registry record. Although the outcome definition, unit, summary measure, dispersion measure, and measurement times are recorded, there is no observed mean, standard deviation, confidence interval, or reported analysis. The record therefore does not allow assessment of the magnitude or precision of the primary endpoint.

The study is open-label, non-randomized, and single-arm, with sequential dose cohorts. There is no randomized comparator described, and the registry record does not report baseline characteristics by cohort. Any contrast between dose cohorts would therefore need cautious interpretation; the information recorded does not show that the groups were comparable or that an analysis adjusted for differences between them.

There is a specific Cohort 1 exclusion note for PK parameter values: one subject was excluded for anomalous and consistently high concentrations, and one for missing concentration data at 1 and 2 hours post-dose. The registry does not report how the anomalous values were identified, whether the exclusion criteria were prespecified, whether the same approach applied to other data, or whether sensitivity analyses were performed. It also does not report the overall amount or pattern of missing PK data.

The safety information is limited to recorded affected counts, at-risk counts, deaths, and selected serious adverse event terms. The registry record does not describe event-level timing, causal attribution, definitions, or statistical comparisons. With non-randomized cohorts, the counts should not be interpreted as a causal comparison of doses.

Finally, the record lists 0 analyses and does not report multiplicity handling, an analysis plan, or a protocol-based sample-size justification. These omissions limit assessment of how results were selected and analyzed. They are gaps in the registry record, not proof that the study lacked such procedures.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Characterize the PK and PD Profile of IV FCM in Pediatric Subjects 1-17 Years Old With IDA — NCT02410213.
• Registry record last updated 2022-07-25; status last verified 2022-07.
• Results first posted 2017-11-29.
• 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

NCT02410213 is a completed Phase II, multi-center, open-label, non-randomized, single-arm study of intravenous ferric carboxymaltose in pediatric subjects aged 1-17 years with iron deficiency anemia. The registry records enrollment of 35 and describes sequential cohorts receiving 7.5 mg/kg or 15 mg/kg, up to a maximum single dose of 750 mg iron, whichever was smaller.

The primary outcome is maximum observed serum concentration (Cmax), measured in µg/mL and summarized as a mean with standard deviation. The concentration profile was specified as prior to dosing and at 1, 2, 6, 12, 48 and 72 hours post dosing. The registry record does not report the primary endpoint results or an analysis.

For Cohort 1, the record notes PK parameter exclusions for one subject with anomalous and consistently high concentrations and one with missing concentration data at 1 and 2 hours post-dose. Safety entries report serious and other adverse event counts and 0 deaths in each cohort. The record lists 0 analyses; broader statistical methods and the primary result are not reported in the registry record.