Bioequivalence Study of Colchicine Tablets: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study of Colchicine Tablets (NCT01021020), a randomized phase 1 study. The primary outcome is Maximal Plasma Concentration (Cmax).

2. Clinical Question

The study title and registry model identify a randomized, three-way crossover design. In general, a crossover compares treatment conditions within participants, which can help account for stable differences between people. The precise treatment sequence, washout details, and analysis of within-participant measurements are not reported in the registry record. Therefore, the listed summary comparisons should be read according to the results actually posted, rather than presumed to represent a paired or formal bioequivalence analysis.

3. Trial Design

The registry describes a randomized, single-dose, three-way crossover study of colchicine tablets and the effect of food. The listed treatment conditions were colchicine 0.6 mg while fasted, colchicine 0.6 mg following a high-fat meal, and colchicine 0.5 mg/probenecid 500 mg while fasted. The study is marked Phase 1, completed, and lists healthy participants as the population.

Enrollment was 28. The primary endpoint summaries report 25 participants for each treatment condition. The safety summaries use different at-risk counts across the treatment conditions. The registry record does not explain these differences, identify the reason for any missing measurements, or state how the reported populations were selected for each analysis.

Pharmacokinetic blood samples were collected before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours after dosing. The endpoint of interest was the maximum plasma concentration. The registry lists the study start as 2007-09 and primary completion as 2007-10.

Although the crossover model is identified, information about treatment sequences, washout periods, blinding, and the statistical handling of repeated measurements is not reported in the registry record. Masking is listed as none. The original sample-size justification and the study’s prespecified analysis plan are also not reported in the registry record, so the planning illustrations should not be mistaken for the design basis of this completed trial.

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: 75 subjects screened, 47 were screen failures

Period I

Reasons for not completing this period:

14 Day Washout Period A

Reasons for not completing this period:

Period II

14 Day Washout Period B

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 Maximal Plasma Concentration (Cmax), measured over serial pharmacokinetic blood samples collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 and 96 hours post-dose.

The primary endpoint was maximal plasma concentration, or Cmax, measured in pg/mL. It represents the highest concentration of colchicine recorded in plasma after dosing. The registry describes it as the maximum or peak concentration reached in plasma.

Cmax is a pharmacokinetic measure: it describes the peak exposure observed over the blood-sampling period. Comparing Cmax across treatment conditions can show whether the observed peak concentrations differ. In this study, that question is relevant to both the food condition and the fasted colchicine/probenecid condition.

Serial sampling matters because the peak may occur between the time of dosing and the end of follow-up. The listed sampling schedule extends from pre-dose through 96 hours post-dose, allowing the recorded concentration profile to be observed over time. The registry reports a mean and standard deviation for each condition.

As a general statistical point, a peak concentration is only one aspect of drug exposure. It does not by itself describe the entire concentration-time profile. The registry lists Cmax as the primary endpoint; it does not provide posted secondary outcome results or a formal bioequivalence decision. The posted mean differences therefore describe this endpoint, not every possible pharmacokinetic or clinical consequence of the treatment conditions.

7. Results Posted in the Registry

• Colchicine (High-fat Meal): mean 2,497 versus 2,503 on control; difference -6.16 (95% CI -399.04 to 386.72), standardized effect d = -0.01; z-test p = 0.975.
• Colchicine 0.5 mg/ Probenecid 500 mg (Fasted): mean 1,706 versus 2,503 on control; difference -797.01 (95% CI -1,155 to -438.65), standardized effect d = -1.23; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: each participant’s Cmax is a numeric concentration in pg/mL. The registry reports the mean and standard deviation for each treatment condition. The mean describes the average recorded peak concentration in that condition. The standard deviation describes the spread of individual observations around that average. A standard deviation is not a confidence interval for the mean, and it does not indicate the precision of a treatment comparison on its own.

What does a mean difference represent?

A mean difference expresses the subtraction of one group mean from another, with its direction determined by the order of the comparison. For the high-fat meal comparison, the reported means were 2497 pg/mL for the meal condition and 2503 pg/mL for fasted colchicine; the listed mean difference was -6.16 pg/mL. For the fasted colchicine/probenecid comparison, the corresponding means were 1706 pg/mL and 2503 pg/mL, and the listed difference was -797.0 pg/mL. A negative value means the first condition in the comparison has a lower estimated mean than the fasted colchicine reference in the posted calculation.

The displayed comparisons include confidence intervals and unadjusted p-values. The p-value is a measure of how compatible the observed data are with a null hypothesis of no mean difference under the assumptions of the calculation. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. An unadjusted p-value also does not account for the possibility of examining multiple comparisons unless an adjustment is made; such an adjustment is not reported in the registry record.

How does the crossover design matter?

In general, a crossover design observes participants under more than one treatment condition. Analyses can account for the fact that measurements from the same participant may be related. That within-participant relationship can affect the standard error and precision of a treatment contrast. The registry identifies a crossover model, but the displayed comparisons are unadjusted mean-difference calculations based on the posted summary statistics. The within-participant correlation, treatment sequence handling, and any period or carryover analysis are not reported in the registry record. The displayed intervals and p-values should not be assumed to incorporate those crossover-specific features.

The registry reports 25 participants for each Cmax condition, alongside overall enrollment of 28. It does not state whether every enrolled participant completed every treatment period or why the summary counts differ from enrollment. Nor does it report a participant flow description or missing-data method. These omissions limit assessment of how the included observations were selected and whether incomplete measurements could affect the comparison.

What is the role of the confidence interval?

In general, a confidence interval gives a range of values compatible with the data and the statistical method used, while reflecting sampling uncertainty. It is not a guarantee that the true effect lies within that particular interval. For the food-condition comparison, the interval runs from -399.0 to 386.7 pg/mL and includes zero. This indicates substantial uncertainty about the direction and size of the mean difference. For fasted colchicine/probenecid versus fasted colchicine, the interval runs from -1155.0 to -438.6 pg/mL. It does not include zero, and the estimate is negative across the interval.

The registry names Cmax as the primary outcome, but does not report the full prespecified statistical plan, transformations, formal bioequivalence criteria, or an adjusted analysis. Cmax comparisons for bioequivalence are often assessed using methods and criteria tailored to that purpose; general practice cannot establish which methods were used in this trial. The record’s available numerical results support interpretation of the posted means and unadjusted differences only.

There are 3 outcome measures listed and 0 secondary outcomes posted. The registry reports 0 analyses. It does not provide further analysis details or explain whether additional analyses were conducted but not entered in the record. Consequently, the results cannot be checked against a complete analysis plan, nor can readers assess whether the posted contrasts were prespecified.

10. Confidence Intervals and Precision

The confidence interval for the high-fat meal comparison is -399.0 to 386.7 pg/mL around a mean difference of -6.16 pg/mL. Because this range crosses zero and extends in both directions, the posted estimate is compatible with a lower mean under the meal condition as well as a higher mean. The interval is broad in relation to the near-zero point estimate, so the data do not pin down the size or direction of the difference precisely.

For fasted colchicine/probenecid versus fasted colchicine, the mean difference is -797.0 pg/mL, with a confidence interval from -1155.0 to -438.6 pg/mL. The range lies below zero, indicating that the estimated mean is lower for the first condition under this comparison. The interval still spans a range of possible difference sizes, so its endpoints matter alongside the point estimate.

In general, confidence intervals communicate both the direction and uncertainty of an estimate. Their width depends on factors such as variability, the amount of information, and the analysis method. The standard deviations reported for the conditions indicate variability in Cmax, but do not by themselves determine the precision of a crossover comparison: paired measurements and their correlation can also matter. The registry does not report the within-participant correlation or the detailed method used for the comparisons.

The intervals are attached to unadjusted mean differences. They are not reported as bioequivalence intervals, and the registry record does not state acceptance bounds for a bioequivalence assessment. Thus, interval interpretation should remain focused on the posted difference in means rather than being treated as a formal bioequivalence determination.

11. 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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design justification. They are participants per arm, not total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario targets the stated fraction of the observed effect: 100%, 75%, or 50%. The original trial’s design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect under the stated calculation assumptions, if that effect and assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not results observed in the completed trial, and they are not observed power.

For the high-fat meal comparison, the observed mean difference was -6.16 pg/mL. Planning for 100% of that observed effect gives 207,778 participants per arm for 80% power and 278,156 participants per arm for 90% power. Planning for 75% gives 369,383 and 494,499 participants per arm, respectively; planning for 50% gives 831,111 and 1,112,622 participants per arm. These very large figures reflect the small observed difference relative to variability in the posted summaries.

For the fasted colchicine/probenecid comparison, planning for 100% of the observed effect gives 11 participants per arm for 80% power and 14 participants per arm for 90% power. Planning for 75% gives 19 and 25 participants per arm; planning for 50% gives 42 and 56 participants per arm. Smaller effects require more participants to detect under the same assumptions. These illustrations do not establish that the completed trial was adequately or inadequately sized for its original objectives.

12. 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 = -6.160; pooled standard deviation σ = 708.698.
2. n = 2 × (1.96 + 0.842)² × 708.698² / -6.160² = 207,777.7, rounded up to 207,778 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 <- -6.15999999999985                      # observed difference in means
sigma <- 708.698211723439                     # 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(1021020)
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 = 207,778 (80% power), 278,156 (90% power)
 75% of observed effect: n per arm = 369,383 (80% power), 494,499 (90% power)
 50% of observed effect: n per arm = 831,111 (80% power), 1,112,622 (90% power)
power.t.test: 207778.7 
Simulated power at n = 207,778 per arm: 0.801 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, identifies Cmax as the primary endpoint, and posts 0 secondary outcomes. It also reports 0 analyses. The record does not describe how the outcomes were selected for reporting, whether other analyses were planned, or whether any results were omitted. The original statistical analysis plan is not reported in the registry record.

There are posted comparisons for the high-fat meal condition versus fasted colchicine and for fasted colchicine/probenecid versus fasted colchicine. The p-values are unadjusted. Whether the trial prespecified these comparisons, whether additional contrasts were evaluated, and whether any multiplicity adjustment was planned or conducted are not reported in the registry record. When multiple outcomes or comparisons are examined, the chance of a false-positive finding can increase unless this is addressed in the analysis plan. This is a general statistical concern, not evidence that a particular adjustment was required or omitted in the trial.

The crossover model raises questions about the analysis population and missing measurements. The registry reports enrollment of 28 and 25 participants in each Cmax condition, but does not report a participant flow, completion status by treatment period, or reasons for missing endpoint data. The safety summaries report different at-risk counts. The record does not explain whether these counts reflect different analysis populations, period-specific availability, or another reason.

The handling of missing data, exclusion criteria, analysis populations, and any sensitivity analyses is not reported in the registry record. It also does not report whether the analysis accounted for treatment sequence, period effects, or within-participant dependence. Without these details, the displayed unadjusted comparisons cannot be fully evaluated as analyses of a randomized crossover study, and readers cannot determine how robust the results are to alternative assumptions about incomplete data or analysis choices.

14. 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 affecting participants in any of the listed safety groups. The at-risk counts were 26 for fasted colchicine 0.6 mg, 27 for colchicine 0.6 mg following a high-fat meal, and 27 for fasted colchicine 0.5 mg/probenecid 500 mg. Death counts are not reported in the registry record, and no serious adverse event terms are listed.

Other adverse events were reported as affecting 5 participants in the fasted colchicine 0.6 mg group, 3 in the high-fat meal group, and 4 in the fasted colchicine/probenecid group. These are counts in the registry’s safety summaries; they should not be read as event rates or as a comparison of risk without further information about event definitions, participant overlap across crossover periods, and the method of analysis.

The safety summaries do not include details about event type or severity beyond the serious-event listing and the count of participants affected by other events. The registry record does not explain the variation in at-risk counts or provide a more detailed safety analysis.

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

The posted results describe mean Cmax under three treatment conditions in healthy participants. The mean for colchicine following a high-fat meal was close to the mean for fasted colchicine, while the unadjusted interval for their difference was wide and included zero. For fasted colchicine/probenecid versus fasted colchicine, the estimated mean difference was negative and the unadjusted confidence interval lay below zero.

These results do not establish that one treatment is clinically better or worse. Cmax is a pharmacokinetic endpoint, and the registry does not report clinical outcomes. The study also concerns healthy participants and a single dose; the record does not establish how these findings apply to other populations, dosing conditions, or uses.

The title describes the study as a bioequivalence study, but the posted result is a comparison of mean Cmax values. The registry does not report formal bioequivalence criteria, a bioequivalence analysis, or a conclusion based on such criteria. The mean-difference results therefore should not be presented as proof of bioequivalence or its absence.

The record does not include detailed crossover analysis methods, the treatment sequences, missing-data handling, or a complete statistical analysis plan. The displayed unadjusted comparisons may not capture the within-participant structure of a crossover design. The reported counts also differ across enrollment, endpoint summaries, and safety groups without an explanation in the registry record. These limits affect how confidently the posted comparisons can be interpreted and reproduced.

The findings are best read narrowly: they summarize the observed peak concentration and the posted unadjusted mean differences for the recorded treatment conditions. They do not answer every question about overall drug exposure, safety, clinical effect, or formal bioequivalence.

16. Why This Trial Matters Statistically

This trial illustrates why endpoint choice and study design need to be read together. Cmax is a peak-concentration measure, and the study used serial pharmacokinetic sampling to capture that peak after dosing. A crossover structure can be useful for comparing treatment conditions within participants, but valid interpretation depends on appropriate handling of repeated measurements, treatment period, and the relationship between measurements from the same person.

The registry identifies the crossover model but posts group means, standard deviations, and unadjusted mean-difference comparisons. It does not report whether the comparisons account for within-participant dependence. That gap is important because the precision of a crossover contrast can depend on the pairing, not only on the separate group means and standard deviations. The posted estimates are still informative as recorded summaries, but they do not provide a complete view of the trial’s analysis.

The two comparisons also illustrate how precision depends on the observed effect relative to variability. The food-condition point estimate is near zero and its interval is broad across values on either side of zero. The colchicine/probenecid comparison has a larger negative estimated difference and an interval that remains below zero. These patterns describe the posted Cmax results, without resolving the formal bioequivalence question.

Finally, planning illustrations based on observed effects can be useful for understanding the scale of future studies, but they do not reveal the original design rationale or constitute evidence of power in the completed study. The registry does not report the original sample-size justification. Keeping these distinctions clear prevents a planning calculation from being mistaken for a trial finding or a substitute for the prespecified analysis.

17. 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 record does not explain why enrollment was 28 while the Cmax summaries list 25 participants per treatment condition. Nor does it explain the at-risk counts of 26 or 27 in the safety summaries. A flow of participants through treatment periods and the reasons for any unavailable observations are not reported in the registry record.

Although the study is identified as a randomized three-way crossover, treatment sequences, washout details, and period-specific information are not reported. The registry does not state whether the posted comparisons account for the within-participant structure, treatment period, or possible carryover. These omissions make it difficult to assess whether the reported uncertainty reflects the intended crossover analysis.

The registry describes the study as evaluating bioequivalence, but does not report formal criteria, an analysis on a ratio scale, or a bioequivalence conclusion. The posted comparisons are unadjusted mean differences in Cmax. The original statistical plan and any multiplicity handling are not reported. The record lists no posted secondary outcomes and no analyses, so the results cannot be compared with a detailed prespecified plan.

The study involved healthy participants and a single dose. Its record does not establish how the pharmacokinetic summaries generalize beyond those conditions. The adverse-event information is limited to affected counts and a serious-event listing; event descriptions, detailed severity information, and death counts are not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Bioequivalence Study of Colchicine Tablets — NCT01021020.
• Registry record last updated 2009-12-09; status last verified 2009-12.
• Results first posted 2009-11-26.
• 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.

21. Record Summary

NCT01021020 is a completed Phase 1 randomized, three-way crossover study titled Bioequivalence Study of Colchicine Tablets. It enrolled 28 healthy participants and evaluated single-dose colchicine under fasted and fed conditions, as well as fasted colchicine/probenecid. The registry lists study start as 2007-09 and primary completion as 2007-10.

The primary endpoint was maximal plasma concentration of colchicine, reported as a mean and standard deviation in pg/mL. The posted summaries list 25 participants per treatment condition. Unadjusted mean-difference comparisons are available for the high-fat meal condition versus fasted colchicine and for fasted colchicine/probenecid versus fasted colchicine.

The registry does not report a formal bioequivalence analysis, detailed crossover methods, missing-data handling, multiplicity procedures, or the original sample-size justification. Safety summaries report no serious adverse events affecting participants in the listed groups, while other adverse-event counts are also posted.