This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Compare the Pharmacokinetic Profiles of Etravil® Tablet 10mg and Etravil® Tablet 25mg (NCT01367080), a randomized phase 1 study. The primary outcome is AUClast and AUCinf.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01367080 |
| Phase | Phase 1 |
| Condition | Depression, Depressive State, Enuresis |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dong Wha Pharmaceutical Co. Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
Healthy male volunteers. The official title identifies this population, and the registry record lists an enrollment of 12. The conditions field also lists Depression, Depressive State, and Enuresis; it does not describe these conditions as eligibility criteria for the volunteers.
Intervention
A single oral administration of Etravil, an amitriptyline hydrochloride tablet, at the 10mg strength. The registry identifies this intervention as DWETR10.
Comparator
A single oral administration of Etravil, an amitriptyline hydrochloride tablet, at the 25mg strength, identified as DWETR25. The crossover sequences list both strengths, with the order reversed between groups.
Primary question
How do plasma exposure measures, AUClast and AUCinf, compare after single oral administration of the 10mg and 25mg tablets? The registry identifies measurement through 72 hours but does not report the observed values or a statistical comparison.
3. Trial Design
This was a randomized, open-label, crossover Phase 1 trial with an enrollment of 12. The official title describes single oral administration in healthy male volunteers. The record identifies two treatment sequences: Group A received DWETR10 first and DWETR25 second, while Group B received DWETR25 first and DWETR10 second. Thus, the planned sequence exposed participants to both tablet strengths, with the order varied between groups.
In a crossover design, each participant can serve as their own comparator because measurements after one treatment can be considered alongside measurements after the other treatment in the same participant. General statistical explanation: this pairing can account for stable differences between participants, but it does not remove the need to consider changes over time, sequence effects, or possible carryover from an earlier treatment. The registry record does not report a washout interval, period-specific procedures, or how these design features were handled analytically.
Randomization identifies how treatment sequence was assigned; it does not by itself establish that all participants completed both periods or that all measurements were available. The record does not report completion counts, an analysis population, or exclusions. Masking is listed as none, so the trial was open-label. Start and primary completion are listed as 2011-07 and 2011-08, and the status is COMPLETED. The sponsor is Dong Wha Pharmaceutical Co. Ltd. The registry record does not report further operational details or the rationale for the enrollment target.
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: 15 participants recruited ; 12 screened, 3 excluded (2 did not meet inclusion criteria and 1 refused participation)
1st Administration
| Stage | A Group | B Group |
|---|---|---|
| STARTED | 6 | 6 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 0 | 0 |
2nd Administration
| Stage | A Group | B Group |
|---|---|---|
| STARTED | 6 | 6 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | A Group | B Group | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 6 | 12 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 6 | 12 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 22.2 (SD 2.1) | 21.2 (SD 2.1) | 21.7 (SD 1.9) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 6 | 6 | 12 |
| Region of Enrollment: Korea, Republic of | participants | 6 | 6 | 12 |
6. Primary Endpoint
The registry lists the primary outcome as AUClast and AUCinf, measured over Up to 72 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng*hr/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled AUClast and AUCinf, with units of ng*hr/mL. AUClast is the area under the plasma concentration-time curve from time zero to the last measured time; AUCinf is the corresponding area extrapolated from time zero to infinity. The registry describes these measures for amitriptyline in plasma and gives a timeframe of up to 72 hours. The listed summary parameter is the mean, with standard deviation as the dispersion measure.
General statistical explanation: area under the curve summarizes drug exposure over time rather than the concentration at a single sampling point. AUClast uses the observed portion of the concentration-time profile, while AUCinf extends that profile beyond the last measured time. These measures are used in pharmacokinetic comparisons because they characterize overall exposure. A mean describes the average endpoint value in a group or treatment condition; a standard deviation describes the spread of individual values around that mean. Neither statistic alone describes the uncertainty in a treatment comparison.
The registry record does not report endpoint means, standard deviations, individual observations, or a comparison estimate. It therefore does not establish the magnitude or precision of any difference between tablet strengths.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized crossover comparison of Etravil 10mg and Etravil 25mg in healthy male volunteers. Its primary endpoint concerns plasma exposure through AUClast and AUCinf. However, the posted results do not include numerical results for either endpoint. No treatment means, standard deviations, between-treatment estimate, confidence interval, or p-value is reported in the registry record. Consequently, the direction, magnitude, and precision of the observed comparison cannot be described from this record.
The record lists Cmax, Tmax, and t1/2 as secondary outcomes, but it does not report their results. It identifies four outcome measures and zero analyses. The endpoint description specifies mean and standard deviation, but those summary statistics are not given. An endpoint definition tells readers what was intended to be measured; it is not itself evidence about the values observed or the relationship between treatments.
General statistical explanation: an estimated treatment difference describes how far apart the observed treatment values are, while a confidence interval describes the uncertainty around that estimate under the analysis assumptions. A p-value addresses compatibility between data and a specified null model; it does not quantify the size or practical importance of a difference. Since these estimates are absent, none of these features can be interpreted for this trial. The enrollment of 12 does not substitute for the missing treatment-specific results.
The crossover sequences make paired comparisons possible in principle. A suitable analysis would need to account for the within-participant structure, but the analysis method is not reported in the registry record. The record also does not say how missing measurements, incomplete periods, sequence, or period effects were handled. Without those details and the outcome estimates, readers cannot assess whether the intended pairing was preserved in the analysis or evaluate the robustness of any result.
The trial's completed status indicates that the study is recorded as completed, not that its findings are fully reported. The available record supports a description of the research question and design, but not a conclusion about how the two formulations compared on exposure measures.
9. Statistical Methods Explained
What does randomization apply to?
The record describes a randomized crossover design with two treatment sequences. Group A was assigned the sequence DWETR10 followed by DWETR25, and Group B the reverse sequence. Randomization in this setting concerns treatment order. General statistical explanation: assigning order randomly can reduce systematic differences between sequence groups, but it does not guarantee that every possible source of bias is eliminated. The randomization method, allocation concealment, and sequence-group sizes are not reported in the registry record.
Why use a crossover design?
In a crossover trial, participants receive more than one treatment in sequence. Since the same participant contributes measurements under both conditions, comparisons can use within-participant pairing. General statistical explanation: pairing can improve precision when measurements from the same person are more alike than measurements from different people, because stable individual differences are accounted for in the comparison. The benefit depends on complete and valid paired measurements and on appropriate handling of period and sequence effects. The record does not report the washout interval, the number of participants completing both periods, or whether the analysis used paired data.
What do mean and standard deviation describe?
The primary endpoint description names the mean as the summary parameter and standard deviation as the dispersion measure. General statistical explanation: the mean summarizes the central value of a continuous measurement, whereas the standard deviation describes variation among observations. A standard deviation is not a confidence interval and does not directly give the precision of a treatment contrast. To assess the contrast, readers need an estimated difference or other comparison measure and its uncertainty. Those results are not reported in the registry record.
What do the pharmacokinetic measures capture?
AUClast and AUCinf summarize exposure over a concentration-time profile, with the former ending at the last measured time and the latter extending to infinity. Cmax, Tmax, and t1/2 are listed as secondary outcomes. General statistical explanation: different pharmacokinetic measures describe different aspects of a profile, so a result for one measure would not automatically establish the result for another. The registry record supplies endpoint names and units for the primary measures but no observed endpoint values or analysis estimates.
How should uncertainty and significance be read?
General statistical explanation: a confidence interval gives a range of values compatible with the data and the assumptions of a statistical model, and its width reflects uncertainty. A p-value is a measure calculated under a specified null hypothesis and model. Neither should be interpreted without the estimate, analysis population, and method that produced it. No confidence intervals or p-values are reported in the registry record, and the record does not describe the statistical model or a testing procedure.
What do planning calculations mean?
The registry record describes planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It distinguishes participants per arm for non-time-to-event calculations from a total event count for time-to-event calculations. These are planning assumptions, not a report of observed power. The record does not state the trial's own sample-size justification or provide the numerical planning illustrations in the statistical information summarized by the registry entry. General statistical explanation: such illustrations depend on the assumed effect and model; they do not establish the precision or significance of the results actually observed.
What remains unspecified?
The record does not report a statistical analysis plan, the handling of missing data, the analysis population, or methods for multiplicity. It also does not report a model for the crossover data or whether treatment, period, or sequence terms were included. The listed number of analyses is zero. Without these details and endpoint estimates, readers cannot reproduce or evaluate a treatment comparison from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists AUClast and AUCinf as primary outcomes and Cmax, Tmax, and t1/2 as secondary outcomes. It does not report how testing across these measures was organized, whether any endpoint was designated as controlling the main inference, or whether a multiplicity adjustment was planned. This matters because, in general, examining multiple outcomes can increase the chance of obtaining at least one apparently unusual result by chance. An adjustment or prespecified testing hierarchy may address that issue, but the registry record does not describe one. No outcome analyses are listed.
Missing-data methods and analysis populations are also not reported in the registry record. The entry does not state how many participants completed both treatment periods, whether all 12 contributed to each endpoint, or how incomplete sampling was handled. General statistical explanation: in a crossover study, missing data in either period can affect the availability of a paired comparison. The consequences depend on why data are missing and on the method used; the record does not provide information to assess either.
The record identifies randomized sequences, but does not specify whether the analysis followed the randomized sequence assignment or used another population definition. It does not state how protocol deviations, incomplete periods, or observations outside the planned sampling schedule were treated. These omissions limit assessment of the analysis, not just interpretation of the endpoint values. Without a documented analysis population, missing-data approach, and multiplicity plan, the statistical handling of the listed outcomes cannot be evaluated from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Etravil 10mg Group | 0 | 12 | 0.0% |
| Etravil 25mg Group | 0 | 12 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Etravil 10mg Group | 2 of 12 |
| Etravil 25mg Group | 2 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Etravil 10mg Group | Etravil 25mg Group |
|---|---|---|---|
| Dizziness | Nervous system disorders | 2 of 12 | 1 of 12 |
| Asthenia | General disorders | 1 of 12 | 1 of 12 |
The safety figures list 12 participants at risk in each treatment group. Serious adverse events are recorded for zero participants in the Etravil 10mg group and zero participants in the Etravil 25mg group. Other adverse events are recorded for 2 participants in each group. The registry record does not provide serious adverse event terms, and deaths are listed as null rather than as a count.
These entries describe the recorded counts; they do not establish that no events occurred outside the categories or reporting period represented in the registry. The distinction between serious and other adverse events is important: the figures for other events should not be read as serious events. The record does not report event-level descriptions, severity, timing, relatedness, or whether the same participant contributed events in both treatment periods.
General statistical explanation: safety counts in a small study are descriptive and can be imprecise. A zero recorded count does not demonstrate that an event is impossible or that the treatments have equivalent safety. The registry record does not provide comparative safety estimates or uncertainty intervals. These figures should therefore be read as the recorded counts for this trial, not as a broad safety conclusion.
12. What the Result Does, and Does Not, Mean
This trial addresses a focused pharmacokinetic question: how plasma exposure measures after a single oral administration of Etravil 10mg compare with those after Etravil 25mg in healthy male volunteers. Its randomized crossover sequences are intended to compare both tablet strengths within participants while varying the order. The primary endpoint is defined using AUClast and AUCinf, and the record lists Cmax, Tmax, and t1/2 as secondary outcomes.
What the registry record does not establish is the observed relationship between the formulations. It contains no reported means, standard deviations, treatment contrast, confidence interval, or p-value for the primary endpoints. It also does not report the secondary outcome values. Without these results, the record cannot show whether one treatment had higher or lower measured exposure, how large any difference was, or how precisely it was estimated.
General statistical explanation: a trial design and a completed status do not by themselves constitute evidence for a specific result. A meaningful interpretation requires the observed data, an analysis suited to the design, and enough methodological detail to understand how the estimate was obtained. For a crossover comparison, readers would also need to know how paired observations and possible period or sequence effects were handled. These analytic details are not reported in the registry record.
The record is useful for identifying the study question, treatment sequence, endpoint definitions, timeframe, and recorded safety counts. It is not a basis for claims about clinical benefit, equivalence, or the overall safety of either strength. Its population is identified as healthy male volunteers, and the comparison concerns single administrations, so the record also does not establish what would occur in other populations or under other treatment conditions.
13. Why This Trial Matters Statistically
This trial is statistically notable for its crossover structure. Rather than assigning participants to receive only one strength, the registry lists two sequences in which both tablet strengths are administered in opposite orders. General statistical explanation: a crossover can make within-person comparisons informative by reducing the influence of stable differences between participants. That design advantage depends on reliable measurements in both periods and appropriate analysis of the paired observations.
The record also illustrates why endpoint definitions and endpoint results must be distinguished. AUClast and AUCinf are specified as primary exposure measures, with a timeframe of up to 72 hours, but numerical results are not reported. A precise definition supports understanding of what was intended to be measured; it cannot answer how the treatments compared. The same applies to the secondary measures Cmax, Tmax, and t1/2.
Randomization of sequence and the recorded enrollment of 12 describe important features of the study, but do not replace reporting of the analysis population, missing-data handling, or treatment estimates. Those details are especially relevant in a crossover design, where incomplete periods can affect paired comparisons. The absence of reported analyses means that readers cannot assess uncertainty, statistical significance, or the consistency of results across endpoints.
The statistical importance of the record is therefore methodological rather than evidential: it identifies a small, randomized, open-label crossover pharmacokinetic study and its intended measures, while leaving the comparative results unavailable. The listed safety counts likewise offer only a limited descriptive account. Transparent outcome and analysis reporting would be needed to support a fuller statistical interpretation.
14. 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 principal limitation of the registry record is that it does not report numerical results for the primary or secondary outcomes. There are no endpoint means or standard deviations, no treatment comparison estimates, and no confidence intervals or p-values. As a result, the central pharmacokinetic comparison cannot be quantified or evaluated for precision.
Several design and analysis details are not reported in the registry record. These include the washout interval, completion by treatment period, the analysis population, handling of missing observations, and methods for accounting for sequence or period effects. The record also does not describe the statistical model, a prespecified testing hierarchy, or multiplicity handling. These details are relevant to judging the validity and interpretation of crossover comparisons.
The record describes healthy male volunteers and single oral administration, so conclusions cannot be extended from this entry to other populations or dosing conditions. Enrollment is listed as 12, but the record does not provide sequence-group counts or endpoint-specific denominators. Safety information is limited to group counts; event descriptions, timing, severity, and relatedness are not reported. Death counts are null.
The record identifies a planning-illustration framework but does not give a sample-size justification for the trial itself. Its completed status does not resolve the missing outcome and analysis information. Together, these gaps prevent independent assessment of the size, uncertainty, and robustness of any treatment comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare the Pharmacokinetic Profiles of Etravil® Tablet 10mg and Etravil® Tablet 25mg — NCT01367080.
- Registry record last updated 2014-08-22; status last verified 2014-08.
- Results first posted 2014-08-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01367080 is a completed randomized, open-label, Phase 1 crossover study sponsored by Dong Wha Pharmaceutical Co. Ltd. It enrolled 12 healthy male volunteers and compared single oral administrations of Etravil 10mg and Etravil 25mg in opposite treatment sequences. The listed primary outcomes are AUClast and AUCinf, measured through 72 hours; Cmax, Tmax, and t1/2 are listed as secondary outcomes.
The registry record does not report numerical pharmacokinetic results, statistical comparisons, or an analysis population. Serious adverse events are recorded for zero participants in each group, and other adverse events for 2 participants in each group. The record does not report serious event terms or a death count.