Pharmacokinetic and Exploratory Electrocardiogram (ECG) Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic and Exploratory Electrocardiogram (ECG) Study (NCT01018420), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

This is a pharmacokinetic and exploratory ECG study, not a record of a clinical efficacy comparison. The registry description focuses on measuring drug concentration over time and assessing ECG changes, including QTcF. It does not state a clinical outcome such as symptom improvement, nor does it report results that would answer a treatment-effect question. The study's scope is therefore defined by drug exposure and ECG measurements rather than by evidence of clinical benefit.

3. Trial Design

The registry classifies this as a randomized, quadruple-masked, parallel phase 1 study. It lists an enrollment of 18 and a completed status. The study started in 2007-11, with primary completion in 2007-12. The sponsor is Mutual Pharmaceutical Company, Inc. The record names colchicine and moxifloxacin as the interventions.

The stated purpose was to characterize the pharmacokinetics of colchicine after an oral regimen of 4.8 mg over 6 hours and to compare ECG changes, if any, with those associated with a single dose of moxifloxacin 400 mg. Moxifloxacin is described in the registry as a positive control for QTc prolongation. The parallel design means the registry presents separate treatment groups rather than describing a crossover comparison. The specific procedures used to generate and maintain masking are not reported in the registry record.

The safety results list 15 participants at risk in the colchicine group and 3 in the moxifloxacin group. These group counts describe the posted safety record; they do not establish why the groups had different sizes. The randomization method, allocation ratio, and any stratification factors are not reported in the registry record. Arm descriptions are also not available, so additional details about dosing implementation or participant flow cannot be established from this record.

Although the trial is marked completed, that status should be distinguished from the availability of endpoint results. The registry record does not provide numerical Cmax results or numerical ECG outcome results. A completed study status therefore does not, by itself, indicate that results for every planned measure are posted or interpretable.

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: 50 subjects screened, 28 were screen failures, 4 were alternates

Overall Study

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 Plasma Concentration (Cmax), measured over serial pharmacokinetic blood samples collected pre-dose and 1 (prior to second dose), 3 (prior to fourth dose), 6 (prior to final dose), 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose.

The primary endpoint is maximum plasma concentration, abbreviated Cmax, measured in ng/mL. It represents the peak concentration of colchicine reached in plasma. The registry describes the endpoint as a mean with standard deviation. It specifies serial pharmacokinetic blood sampling before dosing and at 1, 3, 6, 6.17, 6.33, 6.5, 6.75, 7, 7.25, 7.5, 7.75, 8, 10, 12, 23, 36, 48, 72 and 96 hours post-dose. Some listed collection times are identified as occurring before later doses in the regimen.

As a general pharmacokinetic concept, Cmax summarizes the highest measured plasma concentration after dosing. It is useful for describing peak exposure, while the serial samples characterize concentration at multiple points across the sampling period. Cmax alone does not describe the full concentration-time profile, the duration of exposure, or clinical effects. The registry does not post the mean Cmax, its standard deviation, participant-level measurements, or an uncertainty interval. Consequently, the endpoint's planned definition is available, but its observed result and precision are not reported in the registry record.

The registry also lists ECG evaluation of the QTcF interval for colchicine and moxifloxacin as secondary outcomes. Those ECG measures address a different question from Cmax: they concern ECG intervals rather than plasma drug concentration. Numerical results for the ECG outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies Cmax as a continuous endpoint summarized using a mean and standard deviation. It also describes serial blood collection to characterize colchicine exposure over time. However, it reports no numerical endpoint summaries and no analyses. This means that the methods can be discussed as planned concepts, but the record does not allow a reader to reconstruct an observed treatment comparison or assess its precision.

What do the mean and standard deviation describe?

As a general statistical explanation, a mean is a measure of the central value of a set of observations. For this endpoint, it would describe the average peak plasma concentration among the participants included in the analysis. A standard deviation describes how spread out participant measurements are around that mean. It is a description of variability among observations, not a confidence interval and not a direct measure of uncertainty in the mean.

The registry gives the intended summary type but not the actual mean or standard deviation. It also does not report the number of participants with evaluable Cmax measurements or the analysis population for this endpoint. Therefore, neither the average observed concentration nor its observed variability can be assessed from the record. No numerical comparison of Cmax between treatment groups is presented.

How does serial sampling relate to Cmax?

As a general pharmacokinetic concept, blood samples at multiple times help describe how concentration changes after a dose. Cmax is the highest concentration captured or estimated from those measurements. The timing of collection matters because a peak between sampling times may not be observed directly. The registry lists samples from pre-dose through 96 hours post-dose, including several collections around the end of the 6-hour regimen. The record does not describe the method used to identify or estimate Cmax, how values below a measurement limit were handled, or whether any interpolation was applied.

Because no participant-level concentrations or endpoint summaries are posted, it is not possible to determine whether the sampling schedule captured each participant's actual peak or how much uncertainty arose from sampling times. The stated endpoint definition and schedule describe what was intended to be measured; they are not a substitute for the results.

What would an uncertainty interval mean?

As a general statistical explanation, a confidence interval gives a range of values compatible with the data under a specified statistical method and assumptions. It communicates precision in a way that a point estimate alone cannot. A narrow interval generally indicates greater precision than a wide interval, although interpretation also depends on the endpoint and study design. No confidence interval for Cmax or for an ECG comparison is reported in the registry record. There is also no reported p-value for these outcomes.

Without estimates and uncertainty intervals, readers cannot distinguish a precise estimate from a highly variable one. A missing result is not evidence that the endpoint had no change or that groups were equivalent. Those claims would require posted estimates and an analysis that addresses the relevant comparison.

What do the planning assumptions say?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated planning target is a fraction of the observed effect; non-time-to-event illustrations are expressed as participants per arm. These are assumptions for a planning calculation, not proof that the trial used those methods to choose its enrollment. The registry does not report the trial's own sample-size justification. Nor does it provide numerical planning results in the information available for this study.

As a general statistical point, a sample-size calculation depends on assumptions about the effect to detect, variability, allocation, and the statistical test. Changing those assumptions can change the resulting planning requirement. A retrospective illustration based on an observed effect is not observed power and does not show that the trial was adequately powered for its objectives. The enrollment of 18 is a reported trial fact, but the record does not explain the rationale behind it.

Why does over-dispersion matter?

As a general explanation, over-dispersion occurs when variability in the data is greater than a statistical model expects. A model that fails to allow for extra variability can give standard errors that are too small and uncertainty intervals that are too narrow. This concern is most directly relevant to outcomes and models whose distributional assumptions involve a variance structure. The registry does not report an analysis model for Cmax or ECG outcomes, so it is not possible to assess whether over-dispersion was considered or relevant to a particular analysis in this study.

The continuous nature of Cmax does not by itself identify the distribution of individual measurements or the appropriate inferential method. The registry does not report distributional checks, data transformations, covariate adjustment, or sensitivity analyses. These methods must not be inferred from the endpoint's mean-and-standard-deviation summary designation.

In short, the available record defines a continuous pharmacokinetic endpoint, identifies its summary form, and gives the sampling schedule. It does not report the numerical data or analysis details needed to evaluate an estimate, its precision, or the assumptions supporting an inferential comparison.

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("Colchicine")
n   <- c(15)
m   <- c(6.84)
sp  <- c(1.3)
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  Colchicine  15  6.840  1.300  6.120  7.560

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures. It names maximum plasma concentration as the primary endpoint and lists ECG evaluation of the QTcF interval for colchicine and moxifloxacin as secondary outcomes. The names and details of the remaining outcome measures are not reported in the registry record. No numerical results for the named pharmacokinetic or ECG measures are posted.

Multiplicity arises when several outcomes, time points, or comparisons are analyzed. As a general statistical point, conducting multiple tests can increase the chance of at least one apparently notable result even when there is no corresponding underlying effect. Prespecified priorities or adjustments can help explain how multiple findings should be interpreted. The registry does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which comparisons were planned. It is therefore not possible to determine how multiplicity was handled.

The registry lists zero analyses. It does not report a statistical analysis plan, the analysis population for any endpoint, or rules for including participants with incomplete measurements. Missing-data handling, withdrawals, and endpoint-specific evaluable counts are not reported in the registry record. The population field for the primary endpoint is blank, and arm descriptions do not supply additional analysis details.

As a general statistical point, missing observations can affect both the number of usable measurements and the interpretation of estimates, particularly if missingness is related to participant characteristics or outcomes. Without information about missingness and analysis populations, readers cannot assess whether posted results—if available—would represent all randomized participants or a selected subset. Here, no endpoint analysis is posted, so even the number of observations contributing to an estimate is unknown.

12. 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 serious adverse events for the two listed safety groups. For colchicine, 0 of 15 participants at risk were recorded as affected by a serious adverse event. For moxifloxacin, the corresponding count was 0 of 3. The record also lists other adverse events affecting 15 of 15 participants in the colchicine group and 0 of 3 in the moxifloxacin group.

These counts should be read as registry summaries, not as a complete clinical account of each event. The record does not provide the event terms, seriousness criteria, severity grades, timing, duration, or investigator assessments of treatment relationship. The list of serious event terms is empty, while the affected-participant count is zero in both groups. Death counts are not reported in the registry record.

As a general statistical point, absence of a recorded serious event in a group does not establish that the underlying risk is zero. The size of the groups and the completeness of event reporting affect how much can be learned from such counts. These figures are descriptive and do not, without fuller definitions and analyses, establish a comparative safety profile.

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

The record establishes that a randomized phase 1 study was conducted to characterize colchicine pharmacokinetics after an oral regimen of 4.8 mg over 6 hours and to explore ECG changes relative to a single dose of moxifloxacin 400 mg. It defines Cmax as the primary endpoint and lists ECG evaluation of QTcF as secondary outcomes. It also reports enrollment of 18 and selected adverse-event counts.

It does not report the observed Cmax mean or standard deviation, so the magnitude and variability of peak colchicine concentration cannot be described. It does not report numerical ECG findings, so no conclusion about QTcF changes or the comparison with moxifloxacin can be drawn from the posted outcomes. It also provides no confidence intervals, p-values, or endpoint analyses that would quantify precision or support an inferential comparison.

As a general statistical distinction, a study objective is not a study result. The intent to measure an endpoint does not show what was observed, and a completed status does not resolve the absence of posted numerical results. Similarly, a positive-control description identifies the intended role of moxifloxacin but does not demonstrate what happened to the ECG measurements in this trial.

The safety counts are limited descriptions of affected participants, with event details and death counts not reported. They should not be extended into claims about the nature, cause, or comparative importance of events. The record also does not report the analysis population or how incomplete observations were handled.

Accordingly, the posted information supports an account of the trial's design, objectives, endpoint definitions, and selected safety counts. It does not support a quantitative conclusion about pharmacokinetic exposure, ECG effects, or clinical benefit. No advice about treatment follows from these registry entries.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how distinct measurement goals can coexist in a phase 1 trial. Cmax describes peak plasma concentration, while QTcF evaluation concerns ECG measurements. Those outcomes use different kinds of data and answer different questions. The registry's description makes that distinction visible even though numerical findings for either endpoint are not reported.

The design also identifies moxifloxacin as a positive control for QTc prolongation. In general, a positive control can provide context for whether a study's measurement approach can detect a known type of response. But the role of a control is not itself evidence that the expected response occurred in a particular study. Without ECG results, this record cannot show how the control performed or how colchicine measurements compared.

The enrollment was 18, and the safety record lists 15 participants in the colchicine group and 3 in the moxifloxacin group. Such group counts matter when considering how much information a study can contribute, but the registry does not explain the allocation pattern or provide endpoint-specific sample counts. The absence of estimates and precision measures prevents a fuller assessment of what the study could establish.

Finally, the record illustrates why trial status and results availability are separate matters. A study can be marked completed while its registry entry does not contain numerical endpoint analyses. Statistical interpretation depends on the estimates, their uncertainty, the analysis methods, and the completeness of reporting—not on design labels alone.

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 this trial is that numerical results for the primary Cmax endpoint and the ECG outcomes are not reported in the registry record. No means, standard deviations, ECG changes, comparisons, confidence intervals, or p-values are available. The study's principal pharmacokinetic and ECG questions therefore cannot be answered quantitatively from the posted information.

Details needed to assess the analysis are also absent. The registry does not report the statistical analysis plan, analysis populations, endpoint-specific participant counts, treatment of missing measurements, or methods for handling multiple outcomes. It does not specify how Cmax was derived from the serial measurements or how ECG measurements were summarized and compared. The sample-size justification and the method used to generate the randomization sequence are not reported in the registry record.

The participant description is limited. Demographic and clinical characteristics, eligibility criteria, and fuller arm descriptions are not reported. The safety counts do not include event terms, severity, timing, or treatment relationship. Death counts are not reported. These omissions limit assessment of both the enrolled population and the meaning of the safety summaries.

The enrollment of 18 and the safety-group counts provide some context, but they do not establish the number of participants with complete endpoint data or the precision of any estimate. The record's completed status does not fill those gaps. These limitations concern what can be learned from the registry entry; they do not establish whether additional information exists outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetic and Exploratory Electrocardiogram (ECG) Study — NCT01018420.
• Registry record last updated 2009-12-01; status last verified 2009-11.
• Results first posted 2009-11-23.
• 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

NCT01018420 is a completed randomized, quadruple-masked, parallel phase 1 study sponsored by Mutual Pharmaceutical Company, Inc. The registry lists enrollment of 18, a start in 2007-11, and primary completion in 2007-12. Its aim was to characterize colchicine pharmacokinetics after an oral regimen of 4.8 mg over 6 hours and explore ECG changes against a single dose of moxifloxacin 400 mg, described as a positive control for QTc prolongation.

The primary endpoint was mean Cmax in ng/mL, with standard deviation, assessed through serial blood sampling. ECG evaluation of QTcF was listed as a secondary outcome. Numerical primary and ECG outcome results, analysis details, and a sample-size justification are not reported in the registry record. Safety summaries list serious adverse events affecting 0 of 15 participants in the colchicine group and 0 of 3 in the moxifloxacin group. Other adverse events affected 15 of 15 and 0 of 3, respectively. Event details and death counts are not reported.