Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers (NCT02189941), a randomized phase 1 study. The primary outcome is AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide.

2. Clinical Question

The registry describes a pharmacokinetic pilot study, not a clinical-outcome trial. Its central questions concern drug exposure after a single dose: how exposure with sustained-release deferiprone varies by food condition, and how it compares with immediate-release deferiprone when both are taken while fasting. The record also lists safety and tolerability as a secondary outcome.

Although the study is identified as randomized and crossover, the registry does not report the treatment sequence, the details of allocation, or whether every participant contributed data under every condition. Those details matter when interpreting within-participant comparisons and cannot be reconstructed from the listed conditions alone.

3. Trial Design

This was a Phase 1, randomized, unmasked crossover study sponsored by ApoPharma. It enrolled 11 healthy participants and is listed as completed. The record gives a start of 2014-05 and a primary completion of 2014-06. It describes three single-dose conditions: sustained-release deferiprone after a high fat high calorie breakfast, sustained-release deferiprone under fasting conditions, and immediate-release deferiprone under fasting conditions. Each listed dose was 1000 mg.

A crossover design differs from a parallel-group design because participants may contribute measurements under more than one condition. In general, such designs can support comparisons that account for stable differences between individuals. However, interpretation also depends on sequence, timing between conditions, and whether effects from an earlier condition could carry into a later one. The sequence, washout arrangements, and carryover assessments are not reported in the registry record, so their role in the analysis cannot be evaluated.

The study was unmasked. The registry record does not report further details about how randomization was implemented or whether participants or study staff knew the assigned condition at each stage. It also does not report how many participants completed each condition or contributed evaluable pharmacokinetic data.

The planned pharmacokinetic endpoint was AUCt for serum deferiprone and deferiprone 3-O-glucuronide over a 24-hour interval. The primary population is described as all subjects who contributed evaluable pharmacokinetics data. The record lists safety and tolerability of sustained-release tablets as a secondary outcome. It does not report a protocol-level sample-size justification or a detailed statistical analysis plan.

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: Subjects were randomized to receive 3 single-dose treatments in different sequences, with a washout of 7 days between doses. Twenty (20) subjects were screened and 12 were randomized. One subject experienced a medical event prior to the first dosing and was excluded from the study, so only 11 subjects received at least 1 dose of study product.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who contributed evaluable pharmacokinetics data

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 AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide, measured over 24-hour interval.

AUCt means the area under the concentration-time curve up to the last measured time. In this study, the registry identifies a 24-hour interval and names two analytes: serum deferiprone and its 3-O-glucuronide metabolite. The outcome is continuous, and the record says it was to be summarized using a mean and standard deviation.

Pharmacokinetic exposure measures are used to describe how drug concentrations change over time. AUCt combines information across the sampling interval rather than describing concentration at only one moment. Comparing AUCt across the listed conditions can therefore address whether measured exposure differs between fed and fasting use of the sustained-release formulation, and between sustained-release and immediate-release formulations under fasting conditions. This is a general explanation of the endpoint’s role, not a statement that any particular difference was observed.

The record describes blood sampling before dosing and at multiple post-dose times through 24 hours. It does not report the actual AUCt means, standard deviations, participant-level observations, or estimates comparing conditions. Consequently, the size and precision of any pharmacokinetic contrasts cannot be described from the registry results recorded. Nor can the endpoint alone establish clinical benefit or harm; it measures drug exposure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the endpoint as a continuous measure summarized by a mean and standard deviation. These summaries describe different features of the observed data: the mean indicates the average AUCt, while the standard deviation indicates how spread out individual measurements are around that average. The registry does not report either summary for the primary outcome, so the degree of variation and the observed exposure levels cannot be assessed.

What does a crossover design contribute?

In general, a crossover design can compare conditions within the same participant, which can reduce the influence of stable differences between participants. That advantage depends on valid comparisons across periods and on appropriate handling of sequence and possible carryover. The record labels the design as crossover and randomized, but does not report the treatment sequence, washout details, or a carryover analysis. It is therefore not possible to assess how these design features were addressed.

The record lists a fed sustained-release condition, a fasting sustained-release condition, and a fasting immediate-release condition. These conditions correspond to distinct scientific comparisons: food condition for the sustained-release formulation and formulation under fasting conditions. The registry does not provide a numerical estimate for either contrast. It also does not report whether the analysis used paired comparisons or another model appropriate to the crossover structure.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data and an analysis procedure, and its width conveys precision. A narrow interval indicates more precise estimation than a wide interval, all else being equal. No confidence interval for the primary endpoint is reported in the registry record. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not by itself describe the magnitude or practical importance of an estimated exposure difference. No primary-outcome p-value is reported.

General statistical point: pharmacokinetic measures can vary substantially between participants, and the amount of variability affects how precisely a condition contrast can be estimated. In a crossover study, within-participant variability is especially relevant because comparisons may rely on repeated measurements from the same person. The registry gives neither the primary outcome variability nor the analysis details needed to evaluate that feature.

What do planning illustrations represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. These are planning assumptions, not evidence about how the study was originally designed. Sample-size estimates under such assumptions are planning illustrations and must not be read as observed power. The record does not report the trial’s own sample-size justification or a protocol-level power calculation. Because the primary outcome involves multiple analytes and conditions, a single observed effect may not capture every comparison of interest.

The distinction between an observed effect and a planning target is important. In general, a planning calculation asks what sample size might be needed to detect a specified effect under stated assumptions. It does not show that the study had that probability of detecting an effect after the data have been collected. The registry does not report numerical primary-outcome estimates that would allow readers to assess the observed effects themselves.

Why can variability complicate interpretation?

General statistical point: when data are more variable than an analysis model assumes, uncertainty estimates can be too small and inferential conclusions can be unreliable. In pharmacokinetic work, the measured exposure is continuous and may show participant-to-participant variation. Whether the analysis accounted for the actual distribution of the measurements is not reported in the registry record. No transformations, model assumptions, or diagnostic checks are described.

The record states that the intended summary was the mean and standard deviation. It does not specify whether the analysis used raw or transformed AUCt values, how values below quantification limits were handled, or how incomplete sampling was managed. Those choices can influence estimated exposure and uncertainty, so the absent detail limits independent interpretation. The registry also does not report confidence intervals, adjusted estimates, or the number of observations used for each analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome includes AUCt for two analytes, and the study addresses several condition comparisons. The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. This makes it important to know which contrasts were considered primary, whether additional analyses were planned, and how the chance of false-positive findings across multiple comparisons was handled. A multiplicity strategy is not reported in the registry record.

The registry lists zero analysis entries. It does not give analysis-specific estimates, p-values, confidence intervals, or the number of observations contributing to each endpoint. The primary population is described as subjects with evaluable pharmacokinetics data, but the count and the criteria for evaluability are not reported. The record also does not describe missing-data methods, exclusions, or how incomplete concentration-time profiles were handled.

These omissions matter because a crossover pharmacokinetic study may have repeated measurements within participants and more than one condition contrast. In general, missing observations can affect the set of participants contributing to a comparison, and differing analysis populations can make contrasts less directly comparable. The record does not state whether all randomized participants were included in any analysis or whether analyses followed a prespecified population definition beyond the general evaluable-data description.

The registry does not report an interim-analysis plan, a detailed statistical analysis plan, or procedures for adjusting comparisons. Their absence from the record does not establish that such procedures were or were not used; it means their use cannot be evaluated from this information.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in the listed groups: the sustained-release fed group had 0 among 10 at risk, the sustained-release fasting group had 0 among 10 at risk, and the immediate-release fasting group had 0 among 11 at risk. These figures describe the recorded serious adverse event counts for the stated groups. They do not establish that the risk of a serious event is zero, particularly in a study with a small enrollment.

The record lists other adverse events affecting 5 participants among 10 at risk in each sustained-release group, and 6 among 11 at risk in the immediate-release group. The serious-event and other-event counts are different categories and should not be combined. The registry does not provide the specific terms for these other events in the information recorded here, nor does it give severity, timing, or attribution details.

Death counts are not reported in the registry record. The record lists no serious adverse event terms. These safety counts are descriptive; they do not establish a comparative safety difference between conditions. The groups’ denominators are not identical, and the record does not provide an inferential analysis of safety outcomes.

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

The registry record describes a small Phase 1 pharmacokinetic study in healthy volunteers, with randomized crossover design and three single-dose conditions. Its stated questions concern exposure after sustained-release deferiprone with food and while fasting, and relative bioavailability of sustained-release versus immediate-release deferiprone while fasting. AUCt for serum deferiprone and its 3-O-glucuronide metabolite was the primary endpoint.

What the record does not establish is the numerical answer to those questions. It does not report primary endpoint means, standard deviations, condition contrasts, confidence intervals, or p-values. Without those quantities, readers cannot determine the observed size or precision of an exposure difference from the registry record. The absence of results should not be interpreted as evidence that the formulations or food conditions produced the same exposure.

In general, pharmacokinetic evidence describes drug exposure over time; it does not on its own establish clinical benefit or harm. This study’s population was healthy volunteers, and the registry does not describe a patient population or clinical effectiveness endpoint. The listed secondary outcome concerns safety and tolerability, but the recorded adverse-event counts are descriptive and do not establish a comparative safety conclusion.

The study’s crossover structure may support within-participant comparisons in principle, but the record does not provide sequence, washout, analysis, or evaluable-population details needed to judge how those comparisons were conducted. The listed enrollment count also does not identify how many participants contributed to each primary analysis.

Thus, the registry record is informative about the design and intended measurements, while leaving the central numerical pharmacokinetic findings unavailable. Any conclusion about the direction, magnitude, or clinical relevance of condition differences would go beyond the results reported in the registry.

13. Why This Trial Matters Statistically

This study illustrates why trial design and outcome definition do not substitute for reported results. The registry specifies a continuous pharmacokinetic endpoint, the analytes, the measurement interval, and three dosing conditions. Those details identify the scientific questions clearly, but without AUCt summaries or condition contrasts they do not reveal what exposure differences were observed or how precisely they were estimated.

The crossover design is statistically relevant because it can allow comparisons within participants. In general, this can help distinguish condition effects from stable participant differences. But the value of that design depends on details such as sequence, completeness of repeated measurements, and handling of carryover. Those details are not reported in the registry record, illustrating why design labels alone are insufficient to evaluate an analysis.

The endpoint also raises a multiplicity issue. Two analytes and several condition comparisons are named, while no single comparison is reported as the sole numerical result. In general, readers need to know which contrasts were prespecified and how multiple analyses were interpreted. That information is not present in the registry record.

The study is a useful reminder to separate a planning calculation from evidence about an observed result. Planning illustrations can express sample-size requirements under assumptions, but they do not measure actual study power or replace estimates and uncertainty intervals. The record’s lack of primary numerical results means that the central statistical questions—effect size, variability, and precision—remain unanswered.

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 primary limitation for interpretation is that numerical results for the primary pharmacokinetic endpoint are not reported in the registry record. Means, standard deviations, contrasts between conditions, confidence intervals, and p-values are absent. Consequently, neither the magnitude nor the precision of the primary findings can be assessed.

The record describes 11 enrolled participants but does not state how many contributed evaluable pharmacokinetics data or how many contributed to each condition comparison. Safety denominators are reported, but they should not be assumed to be the primary-outcome analysis denominators. The registry also does not describe exclusions, incomplete profiles, missing-data handling, or the criteria used to classify pharmacokinetic data as evaluable.

Although the design is labeled randomized crossover, the record does not describe treatment sequence, washout arrangements, carryover evaluation, or the statistical model. These details are especially relevant to interpreting repeated condition measurements. The record also does not report a multiplicity procedure despite listing more than one analyte and several condition questions.

The study enrolled healthy volunteers and evaluated single doses. Its registry description therefore concerns pharmacokinetic exposure and safety in that study setting; it does not report clinical outcome evidence. The listed adverse-event counts are limited descriptive information, and death counts are not reported. These limitations leave both primary endpoint interpretation and broader conclusions constrained to the design and aims recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers — NCT02189941.
• Registry record last updated 2016-05-20; status last verified 2016-04.
• Results first posted 2016-05-20.
• 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

NCT02189941 is a completed Phase 1 randomized, unmasked crossover study sponsored by ApoPharma. It enrolled 11 healthy volunteers. The listed conditions were single 1000 mg doses of sustained-release deferiprone after a high fat high calorie breakfast, sustained-release deferiprone while fasting, and immediate-release deferiprone while fasting.

The primary endpoint was AUCt for serum deferiprone and deferiprone 3-O-glucuronide over a 24-hour interval, summarized as a mean and standard deviation. Safety and tolerability was listed as a secondary outcome. The registry reports serious adverse event counts of 0 among 10 at risk, 0 among 10 at risk, and 0 among 11 at risk across the three conditions. Primary pharmacokinetic estimates and analysis details are not reported in the registry record.