Drug-Drug Interaction Study Between Colchicine and Atorvastatin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Drug-Drug Interaction Study Between Colchicine and Atorvastatin (NCT00960323), a non-randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) of Colchicine.

2. Clinical Question

3. Trial Design

This was a phase 1, open-label drug interaction study in healthy volunteers. It was nonrandomized and listed as a single-group study, with no masking. The record describes colchicine pharmacokinetics under a colchicine-alone condition and under a condition in which colchicine was given with atorvastatin at steady state. Thus, the descriptions concern distinct exposure conditions within the study, rather than a randomized, masked comparison between separate treatment groups.

The study enrolled 24 subjects. One subject withdrew before Period II check-in because of a schedule conflict. The registry record lists 24 subjects as enrolled for the primary outcome description, while the adverse-event groups list 23 at risk for the colchicine-and-atorvastatin condition. These figures describe different aspects of participation; the record does not explain the analysis population used for the pharmacokinetic endpoint.

The stated objective was to evaluate the effect of multiple doses of atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. Safety and tolerability were secondary objectives, with adverse events monitored throughout the study period. The primary endpoint was maximum plasma concentration, or Cmax, of colchicine. Serial blood samples were scheduled before dosing on Days 1 and 28 and at specified times through 24 hours after dose administration.

The registry identifies the study as completed, with a start date of 2009-02 and primary completion in 2009-03. It does not report the detailed dosing schedule, protocol rationale, sample-size justification, or statistical analysis plan. The record also cautions that the conditions are not a like-for-like control comparison because allocation was nonrandomized. Therefore, the design description supports a pharmacokinetic question, but does not by itself establish how the comparison was analyzed or how precisely its effect was estimated.

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.

Colchicine Alone

14 Day Washout Period

Atorvastatin Alone

Reasons for not completing this period:

Colchicine and Atorvastatin

Analysis population for the primary outcome, as defined in the registry: 24 subjects were enrolled in this study. One subject withdrew from the study prior to Period II check in due to a schedule conflict.

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) of Colchicine, measured over serial pharmacokinetic blood samples drawn prior to dosing on Days 1 and 28 and then 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after dose administration..

The primary endpoint was the maximum plasma concentration of colchicine, abbreviated Cmax, measured in pg/mL. Cmax is the highest plasma concentration observed over the sampling period after a dose. It is one component of a drug’s concentration-time profile and describes the observed peak exposure, rather than the total amount of drug exposure over time. The registry record defines the endpoint as the maximum or peak concentration colchicine reaches in plasma.

The record specifies a mean and standard deviation for this continuous measure. A mean describes the central level of the recorded values, while a standard deviation describes how spread out individual values are around that mean. These are descriptive summaries; they do not alone show the size or precision of a contrast between conditions. To interpret the effect of atorvastatin on Cmax, readers would need the values under both colchicine conditions and an estimate of their difference or ratio, with uncertainty. Those numerical outcome results and a comparison estimate are not reported in the registry record.

In general, Cmax is used in pharmacokinetic studies because the peak concentration captures one feature of exposure that may change when another drug affects a drug’s handling in the body. It does not represent every aspect of pharmacokinetics. The registry lists serial blood sampling before dosing on Days 1 and 28 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after dose administration. The description does not state how the peak was identified from those samples or whether any model-based estimation was used.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous pharmacokinetic measure: maximum plasma concentration of colchicine, in pg/mL. The registry specifies that the measure is summarized as a mean with a standard deviation. Continuous outcomes can be summarized by a mean when an average level is useful, while the standard deviation conveys the variability among observed measurements. The mean and standard deviation do not, by themselves, establish whether a difference between conditions is statistically clear or clinically meaningful. The registry record does not report the outcome means, standard deviations, or a formal comparison.

What does Cmax describe?

In general, Cmax is the peak concentration observed after dosing during a defined sampling period. It is a feature of the concentration-time profile, not a complete summary of drug exposure. A study can also assess other pharmacokinetic features, but their definitions and results are not reported in the record for this trial. The registry says blood samples were scheduled before dosing on Days 1 and 28 and at multiple times from 0.5 through 24 hours after dosing. The precise rule for choosing the maximum, handling samples that were unavailable, or estimating a peak between scheduled measurements is not reported in the registry record.

How should a condition contrast be interpreted?

For a continuous endpoint, a comparison could be described using the values under each condition and an estimate of the contrast, with an uncertainty interval. The record does not identify whether the analysis compared raw means, within-subject changes, transformed values, or another statistic. This matters in general because the most appropriate comparison depends on the design and on whether the same participants contribute measurements under both conditions. Although the condition descriptions and withdrawal information suggest assessments across study periods, the statistical analysis method and participant-level pairing are not reported in the registry record. No analysis should be attributed to the investigators without that information.

A confidence interval is a general way to express uncertainty around an estimated effect. It helps readers judge which effect sizes are compatible with the data and the analysis assumptions. A p-value, when used, addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the probability that a hypothesis is true or the size of an effect. Neither a confidence interval nor a p-value for Cmax is reported in the registry record. The record lists zero analyses, so no inferential result can be described from the posted registry information.

Why does the design matter?

Random allocation can help balance measured and unmeasured factors between treatment groups on average. This study is identified as nonrandomized, and the registry explicitly warns that its arms are not a like-for-like control comparison. That caution limits how confidently a contrast can be interpreted as an effect attributable only to atorvastatin. General sources of concern in nonrandomized comparisons include study-period effects, differences in the conditions of measurement, and incomplete observations. The record does not say whether the analysis adjusted for any such factors.

The design is also listed as single-group and open-label, with no masking. Open-label means that masking was not used according to the registry entry. For an objective concentration measurement, observer expectations may be less directly relevant than for a subjective outcome, but the open-label design still matters when considering conduct and interpretation. The record does not specify laboratory procedures, assay quality control, or blinded data handling. Those details are not reported in the registry record.

What can the planning assumptions tell readers?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is expressed as a stated fraction of the observed effect. These are assumptions for planning, not evidence that the trial had a particular power, and they do not replace the study’s own design rationale. The registry record does not report that rationale or a sample-size justification. Since the numerical Cmax result and effect estimate are not reported, the effect underlying such an illustration cannot be evaluated from the registry information.

In general, over-dispersion means that variability is greater than a statistical model assumes. When present, it can make standard errors and confidence intervals from a simple model too small, giving an overly precise impression. The record does not report an over-dispersion assessment, a model, or a reason to conclude that over-dispersion was present. This concept is therefore relevant as general statistical context, not as a finding about this study.

The study enrolled 24 subjects, and one withdrew before Period II check-in. In general, missing outcome measurements can affect both the analysis population and the validity of an estimate, especially if missingness is related to a participant’s measurements or study condition. The record does not specify the number of evaluable Cmax observations, the handling of missing values, or whether the analysis included all enrolled subjects. Those missing details prevent a fuller assessment of the statistical methods.

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 Alone", "Colchicine With Atorvastatin")
n   <- c(23, 23)
m   <- c(2023.29, 2487.96)
sp  <- c(903.14, 646.99)
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 Alone  23  2023.290  903.140  1632.743  2413.837
CARM  Colchicine With Atorvastatin  23  2487.960  646.990  2208.181  2767.739

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies maximum plasma concentration of colchicine as the primary outcome and lists three outcome measures overall. It does not give the titles or definitions of the other outcome measures in the information recorded for this analysis. A secondary objective was evaluation of safety and tolerability. The registry lists zero statistical analyses and does not report a statistical analysis plan, a hierarchy among outcomes, or an adjustment for multiple comparisons.

In general, multiplicity arises when several outcomes, time points, treatment contrasts, or statistical tests are considered. If many tests are performed, the chance of at least one apparently unusual result can increase unless the analysis plan addresses this issue. That is a general concern and does not establish that multiple testing occurred in this study. The record does not report which outcomes were formally tested or whether any multiplicity procedure was planned.

Missing-data handling is also not described. The primary outcome description says 24 subjects were enrolled and notes that one withdrew before Period II check-in due to a schedule conflict. The adverse-event groups list 23 at risk for colchicine with atorvastatin and 24 at risk for each of the other listed conditions. These registry entries show that the listed denominators differ by condition, but do not explain the pharmacokinetic analysis set or the reasons for any unavailable concentration measurements.

In general, a complete analysis description would identify which participants and measurements were included, how incomplete observations were handled, and whether assumptions about missingness were made. The record does not report an intention-to-treat or per-protocol population, an imputation method, or a sensitivity analysis. It also does not report whether the study used paired or unpaired statistical methods. These omissions make it difficult to evaluate how the observed data, if available, would relate to the planned question. No missing-data method or multiplicity strategy should be inferred from the endpoint listing alone.

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 lists serious adverse events separately for three conditions. It reports zero subjects affected by a serious adverse event in the colchicine-alone group, with 24 at risk; zero in the atorvastatin-alone group, with 24 at risk; and zero in the colchicine-and-atorvastatin group, with 23 at risk. These are the serious-event counts recorded for the listed groups. The record does not give serious adverse-event terms; the list of top serious terms is empty.

These entries should be read as counts during the recorded study conditions, not as proof that serious events are impossible or that risk is absent. The study enrolled 24 subjects, and one withdrew before Period II check-in. The denominators differ for the combination condition, and the record does not explain whether or how participants may have contributed to more than one condition’s safety group. Deaths are not reported in the registry record.

The record also lists other adverse events affecting 4 subjects with colchicine alone, 6 with atorvastatin alone, and 1 with colchicine and atorvastatin; the corresponding numbers at risk are 24, 24 and 23. These are not serious-event counts and should not be combined with the serious-event figures. The registry does not provide event terms or further details in the information recorded here, so the counts alone do not describe event type, timing, severity, or causal attribution.

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

The record establishes that a phase 1 study was conducted to evaluate the effect of multiple doses of atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine in healthy volunteers. It identifies Cmax as the primary endpoint and gives the sampling schedule and descriptive statistic. It also records a secondary safety and tolerability objective. Those details clarify the question the study was designed to address.

The record does not report the numerical Cmax findings or the statistical comparison between colchicine alone and colchicine with atorvastatin. It therefore does not establish the direction, magnitude, or precision of a difference. A missing result should not be interpreted as a finding of no difference, and it should not be interpreted as evidence of a difference. The registry information is insufficient to quantify the pharmacokinetic effect.

Even if a numerical contrast were available, the design would remain important to its interpretation. The study was nonrandomized, open-label, and listed as a single-group study. The registry specifically warns that the arms are not a like-for-like control comparison. General concerns about nonrandomized comparisons include the possibility that study-period or measurement conditions influence the contrast. The record does not report details that would determine whether such concerns were present or how they were addressed.

The safety counts are also limited. The serious-event counts are zero in each listed condition, but the group sizes are limited and deaths are not reported in the registry record. Those counts describe the recorded observations; they do not establish that rare events cannot occur. The other adverse-event counts are reported separately and do not provide event descriptions or a causal assessment.

Accordingly, the registry record supports a description of the study’s objective, design, endpoint, participant accounting, and recorded adverse-event counts. It does not support a quantitative conclusion about the primary pharmacokinetic comparison, nor a broad conclusion about safety. The distinctions between what the record defines and what it reports as results are essential when interpreting this study.

14. Why This Trial Matters Statistically

This study illustrates a central statistical issue in clinical pharmacology: a well-defined endpoint and sampling schedule are not enough to interpret a treatment-condition comparison. The registry identifies Cmax, specifies its units, and describes the collection of serial blood samples. To assess the question, readers also need the values observed under each condition, an appropriate contrast, and a measure of uncertainty. Those numerical results are not reported in the registry record.

The study also illustrates why design labels matter. The record describes a nonrandomized, open-label, single-group study and cautions that the listed conditions are not a like-for-like control comparison. In general, statistical analysis cannot fully repair design limitations without assumptions, and those assumptions need to be made explicit. Here, the analysis method and any adjustment for period or other effects are not reported. This limits how far an effect can be attributed to atorvastatin from the posted information.

Participant accounting is another important feature. Enrollment was 24, one subject withdrew before Period II check-in, and the at-risk count for the combination condition is 23. These details matter because the number of participants enrolled is not necessarily the number contributing complete measurements to every endpoint. The pharmacokinetic analysis population and treatment of missing data are not reported, so the exact basis for an endpoint comparison cannot be assessed.

Finally, safety counts and pharmacokinetic results answer different questions. The serious adverse-event figures describe recorded event counts, while Cmax concerns a measured drug concentration. Neither can replace the other. The record provides enough information to frame these statistical distinctions, but not enough to evaluate the primary numerical result or the uncertainty around it. This is a useful reminder that registry design descriptions and outcome results must be considered separately.

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 primary limitation for interpreting the intended drug interaction question is that the registry record does not report the numerical Cmax results. It provides no condition-specific means or standard deviations, contrast estimate, confidence interval, or p-value. As a result, the magnitude, direction, and precision of the primary endpoint comparison cannot be assessed from the record.

The nonrandomized allocation is a design limitation explicitly noted in the registry, which cautions that the arms are not a like-for-like control comparison. The study is also listed as open-label and single-group. Details about the order and timing of conditions, period effects, or methods used to address them are not reported in the registry record. The record does not provide enough information to determine whether these factors affected the comparison.

Participant accounting is incomplete for evaluating the pharmacokinetic analysis. Twenty-four subjects were enrolled, and one withdrew before Period II check-in due to a schedule conflict. The at-risk count for the combined condition is 23, compared with 24 for each of the other listed conditions. The numbers of participants with available primary endpoint measurements, the analysis population, and missing-data handling are not reported.

The registry lists three outcome measures but does not identify all of them in the information available for this analysis. It records zero statistical analyses and does not describe an analysis plan, multiplicity approach, sample-size justification, or interim analyses. These details are not reported in the registry record. The absence of this information does not show that a particular method was or was not used outside the record; it limits what can be concluded from the posted data.

Finally, the safety information is sparse. Serious-event counts are listed, but deaths are not reported, and the record does not provide event descriptions for the other adverse events. These limitations constrain interpretation of both the pharmacokinetic objective and the secondary safety objective.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Drug-Drug Interaction Study Between Colchicine and Atorvastatin — NCT00960323.
• Registry record last updated 2010-03-30; status last verified 2010-03.
• Results first posted 2010-03-16.
• 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

This completed phase 1 study evaluated the effect of multiple-dose atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine in healthy volunteers. It was nonrandomized, open-label, and listed as a single-group study. The registry describes colchicine-alone and colchicine-with-atorvastatin conditions and identifies colchicine Cmax in pg/mL as the primary endpoint.

The study enrolled 24 subjects; one withdrew before Period II check-in because of a schedule conflict. The registry record does not report the numerical Cmax results or a statistical analysis of the primary comparison. Serious adverse-event counts are zero for each listed condition, with 24, 24 and 23 subjects at risk, respectively. Deaths are not reported in the registry record. The record cautions that the conditions do not form a like-for-like control comparison.