Drug-Drug Interaction Study of Colchicine and Theophylline: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Drug-Drug Interaction Study of Colchicine and Theophylline (NCT00983905), a non-randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

The study rationale in the registry is that colchicine can suppress hepatic CYP1A2 and that theophylline is a sensitive CYP1A2 probe substrate. On that basis, the study aimed to assess whether co-administration could alter theophylline pharmacokinetics. This is a drug-interaction question about measured drug concentrations, rather than a question about clinical benefit or treatment of a disease.

The study also had a secondary safety and tolerability goal. Participants were to be monitored for adverse events throughout the study period. The registry lists adverse-event counts for several exposure groups, but it does not provide a detailed account of event types beyond the reported counts, nor does it report the primary pharmacokinetic result. Accordingly, the registered question can be described, but the extent or direction of any observed pharmacokinetic change cannot be determined from the registry record.

3. Trial Design

The registry describes a completed Phase 1, open-label, non-randomized study with a single-group model. The official title calls it a one-directional drug-interaction study. It enrolled 30 healthy volunteers. The study began in 2008-08, and primary completion was recorded in 2008-09. The sponsor was Mutual Pharmaceutical Company, Inc.

The stated comparison is theophylline alone against theophylline administered with colchicine at steady state. The former condition is described as baseline theophylline kinetics; the latter as theophylline pharmacokinetics upon administration with steady-state colchicine. The record also lists a Colchicine Alone group for adverse-event reporting. These descriptions do not establish that the exposure conditions were randomized or that they form independent groups. The registry identifies the allocation as non-randomized and explicitly cautions that the arms are not a like-for-like control comparison.

Open-label means the record does not describe masking of treatment conditions. The registry lists masking as none. It does not report a detailed sequence of study visits, the interval between exposure conditions, or how the conditions were assigned. Those details are not reported in the registry record and should not be inferred from the arm labels alone.

The study has three registered outcome measures and no analysis results listed in the record. Maximum plasma concentration is the primary outcome measure. The record provides its measurement description and sampling schedule, but not the measured values, a comparison estimate, or inferential statistics. A sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record.

Because this was not a randomized comparison, a difference between exposure conditions could be difficult to separate from other influences unless the analysis accounts for the study structure and relevant sources of variation. The registry record does not provide enough analysis detail to evaluate that issue. The design and posted information therefore define the intended pharmacokinetic question, but do not by themselves establish the size or precision of an effect.

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: 44 subjects screened, 6 were screen failures, 8 had schedule conflicts

Theophylline Alone

Reasons for not completing this period:

4 Day Washout Period

Colchicine Alone

Reasons for not completing this period:

Theophylline With Colchicine

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 drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration.

The primary endpoint is maximum plasma concentration, abbreviated Cmax. It measures the peak concentration of theophylline in plasma after a dose. The registry describes Cmax as the maximum or peak concentration reached in plasma and specifies that it is summarized as a mean with standard deviation, in µg/mL.

Cmax is used in pharmacokinetic studies because it characterizes the highest measured concentration after dosing. Comparing Cmax under theophylline-alone and theophylline-with-colchicine conditions can help describe whether co-administration is associated with a change in the observed peak concentration. It is one aspect of a concentration-time profile; by itself, it does not describe the entire profile or all pharmacokinetic properties.

The record states that serial pharmacokinetic blood samples were drawn within 1 hour prior to theophylline dosing (0 hour) on Days 1 and 19, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours after theophylline dose administration. A series of measurements allows the peak to be identified from observed concentrations over time, subject to the study’s measurement and analysis procedures. The procedures used to derive each participant’s Cmax are not reported in the registry record.

The endpoint definition and sampling schedule do not provide the actual Cmax values. The mean, standard deviation, comparison estimate, confidence interval, and statistical test result are not reported in the registry record. Without those results, the direction, magnitude, and precision of any difference in peak concentration cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: plasma concentration is measured on a numeric scale, and the registry says Cmax is summarized as a mean and standard deviation. These statistics answer different descriptive questions. The mean represents the average value within the summarized observations. The standard deviation describes how dispersed individual values are around that mean. Neither quantity, on its own, is a direct measure of the uncertainty in a comparison between conditions.

What does a comparison estimate describe?

A comparison estimate expresses the observed contrast between conditions using a defined scale. For this study, a relevant estimate would describe how Cmax under theophylline with steady-state colchicine differs from Cmax under theophylline alone. The registry record does not report such an estimate. Without it, the size and direction of the observed contrast cannot be assessed. A descriptive difference and an inferential conclusion are also not interchangeable: the latter requires an analysis that accounts for the study design and uncertainty.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimate. A narrow interval indicates greater precision under the analysis assumptions, while a wide interval indicates less precision. The interval is not a guarantee that the true value lies within its bounds, nor does it resolve bias from a design that does not support a valid comparison. No confidence interval for the primary endpoint is reported in the registry record.

A p-value, if reported, would describe how compatible the observed data are with a specified null hypothesis under the statistical model. It would not measure the probability that the null hypothesis is true, nor would it quantify the clinical importance of a concentration difference. No p-value or primary endpoint analysis is listed in the registry record. The absence of that result cannot be interpreted as a non-significant finding.

Why does study structure matter?

The registry records non-randomized allocation and a single-group model, and it cautions that the arms are not a like-for-like control comparison. In general, the analysis of repeated exposure conditions may need to account for whether measurements come from the same participants, the order of conditions, and possible period or carryover effects. The record does not provide enough information to establish the analysis structure, whether paired measurements were used, or how order and timing were handled. Those details should not be assumed.

Open-label conduct means treatment conditions were not masked according to the registry. For a laboratory concentration endpoint, the concentration is a measured quantity, but an open-label design can still matter for study conduct, adherence, timing, and other procedures. The registry does not report whether any particular influence occurred, so this is a general design consideration rather than a claim about the study’s conduct.

What do the sampling times contribute?

The registry specifies serial blood sampling from within 1 hour prior to dosing (0 hour) on Days 1 and 19 through 48 hours after theophylline administration. In general, multiple time points are used to characterize the concentration-time profile and identify a peak. The timing and completeness of samples can affect how well a measured peak represents the actual peak. The record does not report individual concentration-time data, sampling deviations, assay details, or the method used to select the maximum concentration.

The study’s Cmax summary is specified as a mean with standard deviation. If observations are highly variable or skewed, a mean and standard deviation may not fully describe their distribution. In general, investigators may consider transformations or alternative summaries when the data and analysis plan warrant them. The registry does not report the distribution of Cmax values or the methods used for any such assessment.

What can be said about sample size?

Enrollment was 30. That is a description of the registered study size, not a statement about how many participants contributed to each endpoint analysis. The record does not report a sample-size justification, target power, or the assumptions used to plan enrollment. A planning calculation based on an observed effect, when available, is an illustration for future studies and is not observed power. No numerical planning results are reported in the registry record.

Power is a design concept describing the chance that a specified analysis will detect an effect of a specified size under its assumptions. It cannot be recovered from an observed p-value, and it does not tell readers whether the observed estimate is precise. Because the registry record does not report a planning justification or the primary endpoint analysis, no study-specific power conclusion can be drawn.

How should analysis details be judged?

A reproducible interpretation would ordinarily need to know the analysis population, the handling of missing measurements, the comparison model, and the way multiple outcomes or tests were addressed. The registry lists three outcome measures but no analysis results. It does not report a statistical analysis plan, interim analyses, or a multiplicity procedure. These omissions mean the intended statistical handling cannot be evaluated from the registry record; they do not establish that no such procedures were used outside the record.

In general, statistical significance and precision are distinct from relevance. A small p-value can accompany an imprecise or modest estimate in some settings, while a non-significant result does not prove equivalence. Equivalence or non-inferiority conclusions require an appropriate design, prespecified margins, and corresponding analysis. None of those details is reported for this study, so no such conclusion is supported by the registry information.

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("Theophylline Alone", "Theophylline With Colchicine (at Steady-state)")
n   <- c(27, 27)
m   <- c(9.76, 9.79)
sp  <- c(2.25, 1.87)
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  Theophylline Alone  27  9.760  2.250  8.870  10.650
CARM  Theophylline With Colchicine (at Steady-state)  27  9.790  1.870  9.050  10.530

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, with maximum plasma concentration identified as the primary measure. It does not report results for the primary endpoint or the other registered measures. A multiplicity plan describing how multiple outcomes or statistical tests were handled is not reported in the registry record. In general, testing several outcomes can increase the chance of a false-positive finding if the analysis does not account for the number and structure of tests. That general concern does not establish that a particular error occurred in this study.

The record lists no analysis results and does not report an interim-analysis plan. It also does not describe a prespecified statistical analysis plan, decision rules, or any adjustment for multiple comparisons. These features should therefore be treated as unreported, rather than assumed to have been absent from the conduct of the study.

Missing-data handling is also not described. Although the registry reports enrollment and safety group counts, it does not report how many participants contributed Cmax measurements, whether any concentration samples were missing, or how incomplete profiles were handled. The reasons for missing data, if any, and the analysis population are not reported in the registry record. This matters because results based on available measurements can be affected when missingness is related to participant characteristics, exposure, or measured concentrations.

The registry’s safety counts do not resolve these endpoint-analysis questions. Safety populations and pharmacokinetic analysis populations can differ, but the record does not specify how these populations were defined. A reader cannot determine whether the primary endpoint was analyzed for all enrolled volunteers or a subset. No conclusions about multiplicity control, missing-data bias, or the analysis population can be drawn from the posted information.

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 zero participants with serious adverse events in each of the three listed safety groups. The groups are Theophylline Alone, Colchicine Alone, and Theophylline With Steady-state Colchicine. The reported numbers at risk are 30, 29, and 27, respectively. These are group-specific registry figures and should not be added together or treated as a count of distinct participants.

For other adverse events, the registry reports counts of 8 for Theophylline Alone, 15 for Colchicine Alone, and 6 for Theophylline With Steady-state Colchicine. The record does not provide an at-risk denominator for these other-event counts. It also does not provide event-level descriptions for those counts in the information, so they cannot be interpreted as counts of a particular symptom or event type.

The death counts are not reported in the registry record; a missing count is not the same as a reported zero. The registry’s list of top serious-event terms is empty, alongside the serious-event counts of zero. These safety data are descriptive and do not establish comparative risk, especially given the non-randomized design and the lack of a like-for-like control comparison. They also do not answer the primary pharmacokinetic question.

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

The registry record describes a pharmacokinetic study designed to examine whether steady-state colchicine affects the peak plasma concentration of a single theophylline dose. It identifies Cmax as the primary endpoint, specifies a sampling schedule, and reports safety counts for several exposure groups. These registry entries establish the study’s focus and some aspects of its conduct.

The record does not report the numerical Cmax results or the statistical comparison. It therefore does not show whether peak concentration was higher, lower, or similar between theophylline-alone and co-administration conditions. It also does not provide an estimate of the size of a difference, its uncertainty, or a statistical test. No conclusion about the presence or absence of a pharmacokinetic effect can be drawn from the missing result.

Even if a Cmax contrast were available, it would address the peak concentration measure, not every aspect of the concentration-time profile. The registry’s broader study aim concerns pharmacokinetics, but a conclusion about other parameters would require their definitions and results. The record states there are three outcome measures, but it does not provide the remaining outcome details in the information reported.

The safety counts are not a substitute for pharmacokinetic results. The reported serious-event counts are zero in the listed groups, while other adverse-event counts are also reported. Those figures are descriptive and must be considered alongside the non-randomized design, the absence of an at-risk denominator for other adverse events, and the lack of reported event details. The death counts are not reported in the registry record.

The study involved healthy volunteers and does not establish what the same exposure conditions would mean for people with a particular illness or for clinical outcomes. The registry’s rationale and aims are not evidence of a specific result. The appropriate reading is limited: the study asked a defined drug-interaction question, but the posted registry information does not contain the primary result needed to answer it.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the distinction between a clearly stated pharmacokinetic question and a reported answer. The registry identifies the exposure conditions, primary measure, summary format, and timing of blood sampling. Those details help readers understand what the investigators intended to measure. However, without the Cmax summaries or comparison estimate, the central statistical question remains unresolved.

The non-randomized design is also important. The registry explicitly cautions that the arms are not a like-for-like control comparison. Statistical interpretation depends not only on the outcome definition, but also on whether the design and analysis support a fair contrast. The record does not give enough detail about condition sequence, pairing, or adjustment to assess how those issues were handled.

The study also demonstrates why uncertainty measures matter. A numerical difference alone would not show how precisely the effect was estimated. Means and standard deviations describe observed values, while an interval around a comparison would help convey uncertainty in the contrast. Neither type of primary result is reported in the registry record, so precision cannot be evaluated.

Finally, the safety reporting illustrates the need to distinguish serious-event counts, other-event counts, denominators, and missing information. The record reports zero serious adverse events in each listed group, counts for other adverse events, and no reported death counts. Keeping these categories separate avoids treating an unreported value as zero or treating descriptive counts as a controlled comparison.

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 this study from the registry record is that the Cmax results are not reported. Without the endpoint values, comparison estimate, or uncertainty measure, the primary pharmacokinetic question cannot be answered from the posted information.

The record identifies a non-randomized design and warns that the arms are not a like-for-like control comparison. Details needed to assess the exposure-condition sequence, whether measurements were paired, and how the analysis accounted for the design are not reported in the registry record. These omissions limit evaluation of the validity of any potential contrast.

The registry reports enrollment of 30, but does not state the number contributing data to the primary endpoint or explain whether any samples were missing. The analysis population, missing-data approach, and reasons for incomplete measurements are not reported. A sample-size justification and detailed statistical analysis plan are also not reported in the registry record.

The study was open-label, and the record does not describe procedures for limiting possible effects of knowledge of exposure condition. The record also does not give the distribution of concentration measurements, laboratory assay details, or the method used to derive Cmax from serial samples. These are relevant considerations for assessing measurement and analysis, but the registry does not establish that any particular problem occurred.

Safety interpretation is limited because the at-risk denominators for other adverse events are not reported, event-level details are not provided, and death counts are not reported in the registry record. The study’s healthy-volunteer population also limits what can be inferred about other populations or clinical outcomes. These limitations do not negate the study’s stated purpose; they define what can and cannot be concluded from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Drug-Drug Interaction Study of Colchicine and Theophylline — NCT00983905.
• Registry record last updated 2010-03-02; status last verified 2010-02.
• Results first posted 2009-09-24.
• 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

NCT00983905 is a completed Phase 1, open-label, non-randomized, single-group drug-interaction study sponsored by Mutual Pharmaceutical Company, Inc. It enrolled 30 healthy volunteers and examined the effect of steady-state colchicine on the pharmacokinetics of a single theophylline dose. The study began in 2008-08, with primary completion in 2008-09.

Maximum plasma concentration (Cmax) was the primary endpoint, specified as a mean with standard deviation and measured through serial blood sampling. The registry record does not report the Cmax results, a comparison estimate, or inferential statistics. It lists three outcome measures and no analysis results.

The registry reports zero participants with serious adverse events in each listed group and other adverse-event counts of 8, 15, and 6. Death counts are not reported in the registry record. Because allocation was non-randomized and the registry cautions that the arms are not a like-for-like comparison, the safety counts should be read descriptively. The primary pharmacokinetic effect and its precision remain undetermined from the posted record.