Study to Evaluate the Interaction Potential of Clarithromycin XL on Diltiazem Hydrochloride Cream 2% in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Interaction Potential of Clarithromycin XL on Diltiazem Hydrochloride Cream 2% in Healthy Subjects (NCT02080780), a na phase 1 study. The primary outcome is Peak Plasma Concentration (Cmax) of 2% Diltiazem.

2. Clinical Question

3. Trial Design

This completed study is registered as Phase 1 and has an open-label, single-group design. Its official title describes a drug-drug interaction study of clarithromycin XL on 2% diltiazem cream in healthy subjects. The record lists enrollment of 24, a start in 2013-09, and primary completion in 2013-10.

The treatment description gives a three-part sequence: a single dose of diltiazem on Day 1, multiple dosing of clarithromycin XL on Days 4-9, and a single dose of diltiazem on Day 8. The primary endpoint is peak plasma concentration of diltiazem. The sequence makes the timing of measurement central to the question: the study is interested in diltiazem concentration before and during the clarithromycin dosing period. However, the registry does not provide the individual concentration measurements or the comparison used to estimate a change.

Allocation is recorded as not applicable, masking is none, and the model is single group. This is not a parallel-group trial with a randomized control arm. Although the registry lists a diltiazem single-dose period and a diltiazem period after clarithromycin, those entries should not be treated as independent, randomized arms. They represent phases in the listed sequence, and the registry does not specify the statistical handling of measurements across phases.

The record lists one outcome measure and no analyses. It does not report a protocol-level statistical analysis plan, a sample-size justification, interim analyses, or further design details. The study status is completed, but that status alone does not show whether the primary question was answered or how precise any estimate was.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Peak Plasma Concentration (Cmax) of 2% Diltiazem, measured over 9 days.

The registered primary endpoint is peak plasma concentration (Cmax) of 2% diltiazem, with units of ng / mL and a 9 days timeframe. Cmax describes the highest measured concentration of a drug in plasma during the specified period of observation. In general, measuring a peak concentration can help characterize systemic exposure after a dose and can be used in a drug-interaction study to assess whether exposure differs with another drug present.

The registry identifies the endpoint as a continuous measure summarized by a mean and standard deviation. In general, the mean describes the center of the observed concentration measurements, while the standard deviation describes how spread out those measurements are around the mean. These summaries do not, by themselves, quantify the difference between the Day 1 and Day 8 measurements or its uncertainty.

The record does not report the Cmax mean, standard deviation, number of measurements contributing to each summary, or an estimated contrast between the diltiazem dosing periods. It also does not provide a confidence interval or a test result. Consequently, the endpoint definition is available, but the registry record does not report the primary endpoint result or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: peak plasma concentration of 2% diltiazem in ng / mL. The registry specifies a mean and standard deviation as the summary type. In general, a mean gives a single measure of the center of a set of observations, while a standard deviation expresses their variability on the measurement scale. A mean and standard deviation can describe a distribution, but they do not provide a direct estimate of the difference between treatment periods unless the period-specific summaries and the analysis are also reported.

What would a treatment-period contrast describe?

For this question, the scientific contrast would concern diltiazem Cmax under the period before clarithromycin and the period after clarithromycin dosing began. The registry lists the first diltiazem dose on Day 1 and clarithromycin dosing on Days 4-9, with a second diltiazem dose on Day 8. In general, a contrast could be expressed as a difference between period means or by another prespecified measure of change. The registry does not report which contrast was planned or used, and no such estimate is reported.

Because the record describes a single group, it would be inappropriate to interpret the sequence as a randomized parallel-group comparison. If measurements from the same participants were linked across periods, an analysis could account for that pairing. In general, paired analyses use the within-person differences, which can distinguish change within a participant from variation between participants. The registry record does not state whether measurements were paired in the analysis, how missing paired measurements were handled, or whether another method was used. The sequence alone does not establish the statistical model.

What does uncertainty add?

An estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data and the analysis assumptions. In general, a narrower interval indicates greater precision and a wider interval indicates greater uncertainty. A confidence interval is not a guarantee that the true effect lies inside it. The registry record does not report an effect estimate or confidence interval for Cmax, so the precision of any possible interaction estimate cannot be assessed from the posted primary outcome information.

A p-value, when reported, addresses how unusual the data would be under a specified null hypothesis and model. It is not a measure of effect size or clinical importance. The registry record lists no analyses and reports no p-value for the primary endpoint. There is therefore no basis for describing a result as statistically significant or not statistically significant.

What assumptions matter for concentration data?

In general, analysis of a continuous endpoint may depend on the distribution of the measurements, the independence or pairing structure, and the adequacy of the model used to estimate the contrast. Concentration measurements can sometimes be skewed, and an analysis may use a transformation or a model suited to the distribution. This is general statistical context, not a description of the method used in this trial. The registry does not report a transformation, distributional assumption, model, or diagnostic assessment.

Over-dispersion is a general concern when observed variation exceeds what a chosen model assumes. If that occurs, standard errors and intervals from a model that understates variability may be too optimistic. The available record does not provide concentration data or model details to assess whether over-dispersion was relevant. No particular distributional problem should be inferred.

The record includes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not a report of the trial’s own design rationale or an observed-power analysis. The record does not report the trial’s sample-size justification, and the primary result needed to anchor an observed-effect illustration is not reported. Such planning illustrations cannot substitute for an effect estimate and its uncertainty.

Recalculated estimates, when based on posted summary statistics, are simple unadjusted recalculations rather than a replacement for a sponsor’s analysis. No sponsor analysis or primary analysis is reported in the registry record, so there is no analysis to compare with a recalculation. The record’s listing of one outcome measure and no analyses should not be read as evidence that a particular statistical test was performed or that a result was null. It means the analysis details and primary endpoint results are not reported in the registry record.

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("Diltiazem Single Dose", "Diltiazem Single Dose After Clarithromycin")
n   <- c(24, 24)
m   <- c(0.34, 0.624)
sp  <- c(0.299, 0.475)
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  Diltiazem Single Dose  24  0.340  0.299  0.214  0.466
CARM  Diltiazem Single Dose After Clarithromycin  24  0.624  0.475  0.423  0.825

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the primary Cmax endpoint, and no analyses. It does not report whether additional outcomes were collected, whether multiple statistical tests were planned, or how multiplicity would have been addressed. Multiplicity is a general concern when many hypotheses are tested: the chance of at least one apparently unusual result can increase as the number of tests increases. No particular multiplicity adjustment can be attributed to this study from the record.

Missing-data methods and the analysis population are also not reported in the registry record. The enrollment is listed as 24, and 24 are listed at risk in each of the three reported periods, but these risk entries do not establish how many participants contributed usable Cmax measurements or whether all measurements were complete. The record does not describe exclusions, withdrawals, missing samples, protocol deviations, or how any such data were handled.

The registry does not identify an intention-to-treat, per-protocol, safety, or pharmacokinetic analysis population. In general, an analysis population definition specifies which participants’ observations contribute to a particular estimate and helps readers understand the scope of the result. Without that definition, and without reported endpoint summaries, it is not possible to assess the impact of missing data or determine the exact population represented by a primary analysis.

These omissions do not prove that data were missing or that multiplicity was a problem. They mean that the corresponding methods and information needed to evaluate those issues are not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports three treatment-period safety entries. For Diltiazem Single Dose, 24 were listed at risk and 0 were listed with serious adverse events; 4 were listed under other adverse events. For Clarithromycin XL (Days 4-9), 24 were listed at risk and 0 were listed with serious adverse events; 3 were listed under other adverse events. For Diltiazem Single Dose After Clarithromycin, 24 were listed at risk and 0 were listed with serious adverse events; 8 were listed under other adverse events.

These are registry entries for each named period, not a randomized comparison. The record does not define the other-adverse-event figures further in the information available, so they should be read as the reported counts without assuming whether they represent unique participants or event episodes. The record lists no serious adverse-event terms. Deaths are not reported in the registry record; a missing death entry should not be interpreted as a reported zero.

Safety counts do not measure the primary pharmacokinetic endpoint and do not provide an estimate of the effect of clarithromycin on diltiazem Cmax. The registry record also does not provide event descriptions, severity details for the other events, or a comparative statistical analysis of safety.

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

The record establishes that a completed, open-label, single-group Phase 1 study was designed to examine the interaction potential of clarithromycin XL on 2% diltiazem cream in healthy subjects. It identifies the treatment sequence and names peak plasma concentration of diltiazem as the primary endpoint. It also provides period-specific safety entries.

Those details describe the research question, but they do not provide its primary answer. The registry record does not report the Cmax means, standard deviations, a comparison between periods, or a confidence interval. It also lists no analyses. The direction and magnitude of any change in diltiazem concentration, and the precision of such a change, are therefore not reported. No conclusion about the presence or absence of an interaction can be drawn from the endpoint results in this record.

The design also limits what a reader can infer from the listed sequence. There is no randomized control arm, and the study is not described as a blinded comparison. A before-and-after contrast in a single sequence can be affected by factors other than the coadministration being studied. In general, randomization and blinding can address some sources of bias, but their absence does not by itself determine the direction of a result. Here, the missing endpoint analysis makes it impossible to evaluate the estimated change or how the study handled other sources of variation.

The safety information should be kept distinct from the pharmacokinetic question. The serious-event entries are zero in each listed period, while the registry reports other-adverse-event figures of 4, 3, and 8 for the respective periods. These figures do not establish a comparative safety effect, and the registry’s death entries are not reported.

Overall, the registry supports a factual description of the design and reported safety counts, but not a conclusion about the primary interaction estimate. The absence of a reported result is not evidence that the result was zero, favorable, unfavorable, or statistically inconclusive.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a clearly stated research question and endpoint are not enough to assess a study’s findings. The registry specifies a single-group sequence, the timing of diltiazem and clarithromycin dosing, and a continuous pharmacokinetic endpoint. Those details identify what was intended to be measured and the broad setting in which the question was asked.

For an interaction question, the treatment-period contrast and its uncertainty are central. An endpoint label alone does not reveal the observed concentrations, the estimated change, or whether the data are compatible with a range of effects. Reporting a mean and standard deviation for each period, a defined contrast, and a confidence interval would help readers assess both effect size and precision. The registry record does not report those results.

The study also highlights the importance of making analysis structure explicit. In a single-group sequence, knowing whether measurements are linked within participants and how that relationship is handled can affect the standard error and interpretation of a contrast. The registry record does not describe the analysis method or the analysis population. Without these details, readers cannot reproduce or evaluate the primary estimate.

Finally, sample-size planning and observed evidence answer different questions. Planning illustrations based on an assumed effect and model do not show what the trial observed, and they are not observed power. This record does not provide the primary effect estimate on which an observed-result interpretation would depend. The statistical importance is therefore less about a reported treatment effect than about the distinction between a registered question and a reported analysis.

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 interpretation is that the registry record does not report the primary Cmax result. No period-specific mean or standard deviation, treatment-period contrast, confidence interval, or p-value is listed. This prevents assessment of the direction, size, and precision of the result that addresses the study’s stated question.

The design is a single-group, open-label sequence without a randomized control arm. The registry lists diltiazem dosing on Day 1 and Day 8, with clarithromycin XL dosing on Days 4-9. The record does not report how the comparison across these periods was modeled or whether participant-level measurements were paired in the analysis. It also does not describe how time-related changes or other potential influences were handled.

Further information about the population is limited. The study title identifies healthy subjects, but eligibility criteria and participant characteristics are not reported in the registry record. Although 24 are listed at risk in each treatment period, the number with evaluable primary endpoint measurements and the analysis population are not reported. Missing-data handling, withdrawals, and exclusions are not described.

The record does not report a statistical analysis plan, multiplicity approach, sample-size justification, or interim-analysis methods. It also does not describe the distributional assumptions or model used for the continuous endpoint. The safety entries provide period-specific counts but lack further detail about other adverse events, while deaths are not reported. These limitations concern what can be evaluated from the registry record; they do not establish that any unreported method or event occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Interaction Potential of Clarithromycin XL on Diltiazem Hydrochloride Cream 2% in Healthy Subjects — NCT02080780.
• Registry record last updated 2014-04-14; status last verified 2014-03.
• Results first posted 2014-04-14.
• 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 is registered as an open-label, single-group drug-interaction study in healthy subjects. The listed sequence includes a single dose of 2% diltiazem on Day 1, clarithromycin XL on Days 4-9, and another single dose of diltiazem on Day 8. Enrollment is listed as 24.

The primary endpoint is peak plasma concentration of 2% diltiazem, in ng / mL, over a 9 days timeframe, with the mean and standard deviation specified as summary measures. The registry lists one outcome measure and no analyses. It does not report the primary endpoint values or an estimated interaction effect.

The safety entries list 0 serious adverse events in each period and other-adverse-event figures of 4, 3, and 8, respectively. Deaths are not reported in the registry record. The record supports a description of the study design and registered question, but does not provide enough primary outcome information to assess the interaction estimate or its precision.