Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects (NCT01860703), a randomized phase 4 study. The primary outcome is Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, crossover trial described as a thorough QT/QTc study. The registry lists triple masking and a randomized allocation. The study was single-dose, placebo and active controlled, and used four treatment periods. It enrolled 50 healthy subjects and is listed as completed. The registry records a start in 2012-11 and primary completion in 2012-12.

The treatment conditions were a single 33 mg/kg dose of deferiprone, a single 50 mg/kg dose of deferiprone, placebo, and a single 400 mg moxifloxacin tablet. The 33 mg/kg and 50 mg/kg doses were rounded to the nearest 250 mg. Moxifloxacin was the positive control; placebo was the primary comparison control for the deferiprone endpoint. Because the design was crossover, subjects could contribute observations under different treatment conditions, but the sequence and period-specific allocation details are not reported in the registry record.

The primary outcome was the maximum difference in change from baseline in ddQTcF following the 33 mg/kg dose. ECG measurements were collected in a 24-hour interval, with predose and postdose recording times specified in the outcome description. The primary analysis population required treatment exposure and valid QT/QTc readings at predose and at least one postdose time point. It included 46 subjects for the deferiprone arm and 45 for placebo.

The registry lists ten outcome measures and three analyses, along with six posted secondary outcomes. The trial's original sample-size assumptions, treatment-sequence details, and full statistical analysis plan are not reported in the registry record. The sample-size illustrations associated with the posted effect are separate from the trial's original design.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).

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: Fifty subjects were enrolled in order to have at least 33 subjects complete the study. The sample size calculations were based on the ICH E14 Guidance which defines a negative TQT study as one "in which the upper bound of the 95% one-sided CI for the largest time-matched mean effect of the drug on the QTc interval excludes 10 msec."

6. Primary Endpoint

The registry lists the primary outcome as Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone, measured over 24-hour interval.

The primary endpoint is the maximum difference in change from baseline in ddQTcF after a single 33 mg/kg dose of deferiprone, compared with placebo, over a 24-hour interval. QTcF refers to the QT interval corrected for heart rate using Fridericia's method. The outcome description states that QTcF change was assessed by comparing the postdose change from baseline between treatment and placebo at each time interval, then identifying the maximum difference.

ECG recordings were scheduled before dosing and at postdose times through Hour 24. The analysis population required valid Day 1 QT/QTc measurements before dosing and at least one after dosing, in addition to randomization and receipt of at least one study dose. The posted endpoint is expressed in milliseconds and summarized as a least-squares mean with standard deviation.

General: QT correction is used because heart rate affects the measured QT interval; a corrected interval aims to make comparisons less dependent on heart-rate differences. A maximum difference across scheduled times focuses attention on the largest measured treatment-placebo contrast during the specified interval. That summary does not, by itself, describe every time-specific result or establish the clinical importance of a difference. The registry record does not report a clinical threshold for interpreting the size of this endpoint.

7. Results Posted in the Registry

• 33 mg/kg Deferiprone: mean 1.40 versus -1.60 on control; difference 3.00 (95% CI 1.02 to 4.98), standardized effect d = 0.62; z-test p = 0.003.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Placebo Control: mean 1.20 versus 14.70 on control; difference -13.50 (95% CI -16.14 to -10.86), standardized effect d = -2.10; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Placebo Control than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover adverse events, deferiprone and metabolite pharmacokinetics, and a QTcF comparison involving moxifloxacin. The registry lists six secondary outcomes, but detailed numerical results are not available for all of them in the record summarized by these registry entries. Results for those outcomes are not reported in the registry record, so they cannot be used to describe a complete pattern across all secondary measures.

The available numerical secondary QTcF result concerns the positive control. Its posted comparison is distinct from the primary deferiprone-placebo contrast and serves a different role in the trial design. It should not be treated as a second estimate of the primary deferiprone effect. The numerical result is reported in the associated outcome data; the broader secondary outcomes do not all have corresponding numerical details in the registry record.

Secondary outcomes can add context about the study, but they do not replace the prespecified primary question. They may involve different measurements, contrasts, and analysis populations. Moreover, when multiple outcomes and comparisons are tested, unadjusted results carry less weight as confirmatory evidence because repeated testing can produce apparently notable findings by chance. The registry record does not report a multiplicity strategy, a testing hierarchy, or adjustments across the secondary outcomes.

Accordingly, the secondary results should be read as supportive or descriptive, depending on their stated purpose and analysis, rather than as a single unified conclusion. The primary inference remains tied to the 33 mg/kg deferiprone versus placebo comparison. The record does not support extending that result to every secondary outcome, or claiming a consistent pattern across secondary endpoints whose numerical findings are not reported.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Adverse Events
• Cmax of Deferiprone and Deferiprone 3-O Glucuronide
• Tmax of Deferiprone and Deferiprone 3-O-glucuronide
• AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide
• T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
• Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin

9. Statistical Interpretation

10. Statistical Methods Explained

The endpoint is continuous and measured in milliseconds. The registry identifies the reported arm summaries as least-squares means with standard deviations. A mean describes the central value of a continuous measurement; a standard deviation describes how spread out individual measurements are around that mean. These summaries provide context for the comparison, but they do not show the complete distribution of individual readings or how measurements within the same subject were related across crossover periods.

What does a mean difference represent?

A mean difference expresses the estimated contrast between two group summaries in the outcome's units. For the primary comparison, the posted summaries are 1.4 milliseconds for deferiprone and -1.6 milliseconds for placebo, and the recalculated difference is 3.0 milliseconds. The positive direction means the deferiprone summary is higher than the placebo summary under the stated contrast. This is an estimate, not a claim that each subject experienced a change of that size.

General: a difference is often easier to interpret than two separate means because it directly describes the contrast of interest. Its meaning still depends on how the endpoint was defined, the population analyzed, and the comparison method. Here the endpoint is the maximum difference in change from baseline in ddQTcF, not simply an unqualified QTcF value at one time point.

What does the interval add?

A confidence interval expresses uncertainty around an estimate under a specified statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. The recalculated primary comparison has endpoints 1.019 and 4.981 milliseconds. The registry's reported sponsor analysis gives a 90% confidence interval from 1.02 to 5.01 milliseconds for its reported mean difference of 3.01 milliseconds. Those ranges arise from different posted summaries and should be interpreted in their own analysis contexts.

General: a confidence interval is not a range that guarantees the true value lies within its endpoints. Its coverage interpretation depends on the method and assumptions used. In repeated applications of a procedure with the stated confidence level, intervals would contain the fixed parameter at the procedure's nominal rate if the assumptions held. The registry record does not state a confidence level for the recalculated interval, so no confidence level should be assigned to it from the posted comparison alone.

Why does the crossover design matter?

In a crossover design, treatment comparisons may draw on repeated observations from the same subjects. Such observations are usually related rather than independent. An analysis can use that within-subject pairing, and its precision depends in part on the degree of association between measurements within a subject. The registry record identifies the design as crossover, but does not report the treatment sequence, the correlation between repeated measures, or the detailed model used for the sponsor's primary analysis.

The recalculated comparison is based on posted arm-level summaries and an approximate pooled standard deviation. It does not reconstruct subject-level paired differences. Without subject-level data or the relevant covariance information, the within-subject contrast and the exact uncertainty from a crossover model cannot be recovered from these summaries. The recalculation is therefore a useful simple check on the reported scale and direction, but not a substitute for the sponsor's design-specific analysis.

What does the p-value say?

The posted unadjusted p-value is 0.003. General: a p-value is calculated under a null hypothesis and a statistical model; it describes the compatibility of the observed data, or more extreme data, with that model. A small p-value can indicate that the data are difficult to reconcile with the null model under its assumptions. It does not measure the size or clinical importance of the difference, and it is not the probability that the null hypothesis is true.

The value is unadjusted, so it does not account for the presence of multiple endpoints or comparisons. The registry record does not report whether the primary p-value was adjusted, whether there was a prespecified hierarchy, or how the analysis handled the broader family of tests. A reader should distinguish the posted p-value from a family-wise inference across all trial outcomes.

Why can over-dispersion matter?

General: over-dispersion means that observed variation is greater than a statistical model expects. When a model understates variability, standard errors can be too small and intervals too narrow, making results appear more precise than they are. This concept is especially relevant to count outcomes or models with an assumed mean-variance relationship. The primary endpoint is continuous, and the registry record does not report an over-dispersion assessment for it. The concept should not be taken as evidence that over-dispersion occurred in this trial.

For this continuous outcome, the reported standard deviations describe variability in the posted arm summaries. Those values alone do not verify that every model assumption held, nor do they show the distribution of residuals or within-subject correlations. The record does not report diagnostic checks, the exact model specification, or any sensitivity analysis addressing these issues.

What can be inferred from the analysis record?

The registry reports one sponsor analysis of the primary comparison, with a 90% confidence interval, and an unadjusted recalculation is also available from summary statistics. The sponsor's analysis is the analysis reported for the trial; the recalculation is a secondary statistical reading. The registry record does not report the original sample-size justification, the complete analysis plan, interim analyses, treatment sequence, or detailed handling of missing ECG readings. Absence of those details limits assessment of how prespecified decisions align with the posted results. It is not evidence that a particular procedure was or was not used.

General: sound interpretation combines the estimate, its uncertainty, the design, the endpoint definition, and the analysis population. No single statistic supplies all of that context. For this trial, the design is crossover, the primary population has specified ECG availability requirements, and the estimate concerns a single dose and one endpoint definition. Those details define the scope of the statistical result.

11. Confidence Intervals and Precision

The primary recalculated mean difference is 3.0 milliseconds, with interval endpoints 1.019 and 4.981 milliseconds. This interval communicates uncertainty around the estimated contrast and is more informative than the point estimate alone. The registry record does not state a confidence level for this recalculated interval, so its endpoints should not be described as a 90% or 95% interval.

The sponsor's reported analysis gives a mean difference of 3.01 milliseconds and a 90% confidence interval from 1.02 to 5.01 milliseconds. Its estimate and interval are close to the recalculated comparison, but the reported analysis is defined as a mean difference in final values, while the recalculation is based on posted summary statistics. The distinction in estimands and methods means the two ranges should not be collapsed into one result.

General: interval precision depends on the amount of information, the variability of the outcome, and the statistical model. A narrower interval signals less uncertainty under the model, but it does not remove possible bias, measurement limitations, or uncertainty about how well the model represents the design. Because this is a crossover study, within-subject dependence can affect precision. The subject-level covariance needed to reproduce a paired analysis is not reported in the registry record.

The primary analysis population included 46 subjects for deferiprone and 45 for placebo. These are the analysis counts for the posted primary comparison, not the original enrollment total. The registry does not explain all differences between enrollment and the analysis counts, so exclusions or missing measurement patterns should not be inferred from the counts alone. The interval quantifies sampling uncertainty under the relevant analysis; it does not account automatically for missing-data bias, multiplicity, or the limits of generalizing from healthy subjects.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are planning illustrations based on the observed effect and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not observed properties of the completed trial. They do not tell how likely the trial was to have detected an effect after the results were observed. This is not observed power.

The rows use planning for 100%, 75%, and 50% of the observed effect. In the primary comparison, the listed participants per arm for 80% power are 41, 73, and 163, respectively; the corresponding participants per arm for 90% power are 55, 97, and 218. The pattern illustrates a general point: smaller effects are harder to distinguish from random variation, so planning for a smaller effect requires more participants under the same assumptions.

These calculations assume equal allocation and use a normal approximation. They do not reproduce the crossover design's within-subject structure, because the planning assumptions describe a two-arm calculation and the required subject-level correlation is not reported. The figures should therefore be read as illustrations tied to the posted effect and stated assumptions, rather than as a reconstruction of the original trial's design process.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.000; pooled standard deviation σ = 4.822.
2. n = 2 × (1.96 + 0.842)² × 4.822² / 3.000² = 40.6, rounded up to 41 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 3                      # observed difference in means
sigma <- 4.82216045571631                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1860703)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 41 (80% power), 55 (90% power)
 75% of observed effect: n per arm = 73 (80% power), 97 (90% power)
 50% of observed effect: n per arm = 163 (80% power), 218 (90% power)
power.t.test: 41.5 
Simulated power at n = 41 per arm: 0.790 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor's primary analysis as a mean difference in final values of 3.01 milliseconds, with a 90% confidence interval from 1.02 to 5.01 milliseconds. No p-value is listed for that analysis. The unadjusted recalculation gives a mean difference of 3.0 milliseconds, an interval from 1.019 to 4.981 milliseconds, and an unadjusted p-value of 0.003.

The sponsor estimate and the recalculated estimate are very close in numerical value, and both indicate a positive deferiprone-placebo contrast. Their intervals have similar endpoints but are not identical. The sponsor analysis is the trial's reported analysis; the recalculation is based on the posted summary statistics and uses an approximate pooled standard deviation. The registry does not report enough detail to establish that the estimands and statistical procedures are identical.

Because the discrepancy flag is false, the posted summaries do not identify a discrepancy requiring a different interpretation. The sponsor's reported analysis remains the primary record of the trial analysis, while the recalculation provides a simple, unadjusted cross-check. The registry record does not report the sponsor model specification or the reason for any small numerical differences between the two estimates.

15. Multiplicity, Missing Data and Analysis Populations

The trial includes multiple treatment conditions and multiple outcomes. The primary endpoint compares 33 mg/kg deferiprone with placebo; the design also includes a 50 mg/kg dose and a positive-control treatment. The registry lists ten outcome measures and three analyses, including secondary measures of adverse events and pharmacokinetics. Considering several outcomes or treatment contrasts can create multiplicity: the more statistical tests conducted, the greater the chance that at least one will appear notable even when its null hypothesis is true.

The primary comparison has an unadjusted p-value of 0.003. The registry record does not report whether a multiplicity adjustment was applied, whether outcomes were tested in a prespecified order, or whether a testing hierarchy controlled the interpretation of later results. It also does not report a broader family of tests or a strategy for interpreting secondary results. Thus the posted p-value should be understood as unadjusted, not as evidence that multiplicity has been controlled.

The primary analysis population is defined as randomized subjects who received at least one dose and had valid Day 1 QT/QTc measurements at predose and at least one postdose time. This is a stated available-measurement requirement. The registry record does not report the number or reasons for subjects excluded from the primary analysis, the amount and pattern of missing ECG data, or the method used to handle missing measurements. The analysis counts alone do not identify why subjects were not included.

The record also does not report whether interim analyses were conducted, the full statistical analysis plan, or the detailed model used for the sponsor's crossover analysis. These details are important for assessing prespecification, handling of repeated measurements, and the relationship between the analysis and the design. Their absence from the registry record limits methodological appraisal; it should not be interpreted as proof that a procedure was omitted.

General: multiplicity, missing data, and analysis-population choices affect how confidently results can be generalized from a set of estimates. They are distinct issues. Adjustment for multiple testing does not resolve bias from missing measurements, and a clearly defined analysis population does not establish that all missing-data assumptions are valid. The available record supports interpretation of the posted endpoint and estimates, but not a complete audit of these decisions.

16. 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's adverse-event summary lists zero serious adverse events in each treatment condition. The at-risk counts are 46 for the maximum therapeutic dose arm, 48 for the supratherapeutic dose arm, 45 for placebo control, and 46 for the positive control. The registry record does not report deaths for these groups.

These are participant counts for the listed treatment conditions, not a complete description of event severity, timing, or relation to study treatment. The registry also reports counts for other adverse events, but the serious-event figures alone do not describe the overall safety experience. The record does not provide serious-event terms because no top serious terms are listed.

General: a zero count in a trial summary means no serious adverse events were recorded in the reported group data; it does not establish that the underlying risk is zero. Interpretation depends on the number of participants, duration of observation, event definitions, and completeness of reporting. This study involved single-dose administration in healthy subjects, so the safety summaries should be read within that study context rather than generalized to other dosing or populations.

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

The primary posted result describes a positive mean contrast of 3.0 milliseconds for 33 mg/kg deferiprone versus placebo in the maximum difference in change-from-baseline ddQTcF endpoint. The recalculated interval extends from 1.019 to 4.981 milliseconds, and the unadjusted p-value is 0.003. The sponsor analysis reports a closely sized difference of 3.01 milliseconds with a 90% confidence interval from 1.02 to 5.01 milliseconds.

Statistically, the data indicate a difference between the posted treatment and placebo summaries under the relevant analyses. The estimate and interval describe the size and uncertainty of that contrast. They do not, on their own, determine whether the difference is clinically important. The registry record does not provide a threshold for clinical interpretation of this endpoint, and the p-value does not measure clinical importance.

The result applies to the stated endpoint, dose, comparator, analysis population, and 24-hour measurement interval. It is not a numerical result for the 50 mg/kg dose, a comparison with moxifloxacin, or an estimate for repeated dosing. It also comes from healthy subjects and cannot by itself establish how the result applies to other populations. The registry record does not report outcome values for all the other treatment and secondary comparisons.

The trial's crossover design and its stated analysis population are relevant to interpretation. The recalculation uses posted group summaries and does not recreate a subject-level paired analysis. The registry's sponsor analysis is the reported trial analysis, but detailed model and missing-data methods are not reported in the registry record. These limitations affect how much of the analysis can be independently assessed from the posted information.

Nothing in the statistical result alone establishes an individual outcome or provides a treatment recommendation. It is a summary of group-level ECG measurements under the trial conditions. The data do not answer every question about longer-term exposure, other doses, other populations, or the clinical consequences of a QTc difference.

18. Why This Trial Matters Statistically

This trial is statistically informative because it frames a specific continuous ECG endpoint as a treatment-placebo contrast over a defined interval. Reporting the estimate in milliseconds, alongside uncertainty, helps distinguish the size of the observed contrast from the strength of evidence against a zero-difference model. The sponsor's estimate and the summary-statistic recalculation are close, while their method descriptions are not identical.

The crossover design makes the analysis structure consequential. Repeated treatment observations from the same subjects can carry within-subject information, and a design-aware analysis may use it. At the same time, a simple recalculation from group summaries cannot fully reproduce that structure without subject-level data or covariance information. This is an example of why the design and the reported estimand matter when interpreting a point estimate and its precision.

The trial also illustrates the distinction between a primary endpoint and a wider collection of outcomes. The primary result has an unadjusted p-value, while the registry includes multiple treatment conditions and secondary outcomes. Without a reported multiplicity plan, isolated secondary findings should be interpreted cautiously and kept separate from the primary comparison.

Finally, the planning illustrations show how sample-size requirements depend on the effect selected for planning. Smaller target effects require more participants under the stated assumptions. Those calculations do not reconstruct the trial's original design rationale, which is not reported in the registry record, and they are not observed power. Together, these statistical features make the record useful for learning how design, effect estimation, precision, and multiplicity shape interpretation.

19. 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 numerical result concerns the 33 mg/kg deferiprone dose. Although the trial also included a 50 mg/kg dose, numerical findings for that dose are not reported in the registry record in the registry record for this analysis. The 33 mg/kg estimate should therefore not be treated as a result for the supratherapeutic dose or as evidence of a dose-response pattern.

The study enrolled healthy subjects and used single-dose treatment conditions. Its results do not directly describe other populations or repeated dosing. The primary endpoint summarizes a maximum treatment-placebo contrast over 24 hours, so it does not fully describe the trajectory at every ECG recording time. The record does not report a clinical threshold for interpreting the endpoint magnitude.

The crossover design raises the importance of within-subject analysis. The posted summary statistics do not include individual data or the covariance between repeated measurements, and the registry record does not report enough detail to reproduce the sponsor's model. The recalculation is consequently an approximate, unadjusted summary-statistic comparison rather than a reconstruction of the full crossover analysis.

The registry record does not report the original sample-size justification, a full statistical analysis plan, treatment-sequence details, interim analyses, the multiplicity strategy, or detailed missing-data handling. It also does not report numerical results for all listed secondary outcomes. These omissions limit independent assessment of prespecification, robustness, and the breadth of the findings. They do not demonstrate that the trial failed to address these issues; they indicate that the relevant information is not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects — NCT01860703.
• Registry record last updated 2014-11-12; status last verified 2014-11.
• Results first posted 2014-11-12.
• 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.

23. Record Summary

The registry identifies a completed Phase 4 randomized, triple-masked, crossover trial of deferiprone and QTc interval in healthy subjects. The study enrolled 50 subjects and compared single-dose deferiprone at 33 mg/kg and 50 mg/kg with placebo, with moxifloxacin as a positive control. The primary endpoint was the maximum difference in change from baseline in ddQTcF after 33 mg/kg deferiprone over a 24-hour interval.

For the primary comparison, the posted means were 1.4 milliseconds for deferiprone and -1.6 milliseconds for placebo. The recalculated mean difference was 3.0 milliseconds, with interval endpoints 1.019 and 4.981 milliseconds and an unadjusted p-value of 0.003. The sponsor-reported mean difference was 3.01 milliseconds, with a 90% confidence interval from 1.02 to 5.01 milliseconds. The registry record does not report several details needed to reconstruct the full crossover analysis, assess multiplicity, or evaluate missing-data handling.