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 Potential for Drug-drug Interactions Between Boceprevir and Etravirine in HIV/Hepatitis C Virus Negative Volunteers (NCT01427504), a randomized na study. The primary outcome is Boceprevir AUC Pharmacokinetics.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01427504 |
| Phase | NA |
| Condition | Hepatitis C, HIV |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
The study involved HIV- and hepatitis C-negative volunteers. The registry record lists an enrollment of 26 and says the number of participants for the primary outcome was based on completing all three medication sequences. The number who completed all sequences is not reported in the registry record.
Intervention
The medication conditions were boceprevir alone, etravirine alone, and the two drugs taken together. The official title specifies boceprevir 800mg thrice daily and etravirine 200mg twice daily. The registry record describes six randomized orders for these conditions.
Comparator
The primary outcome concerns boceprevir AUC when administered alone. The study’s broader rationale concerns possible changes in drug concentrations during coadministration, so the medication-alone conditions provide context for the combined condition. A primary statistical comparison between conditions is not reported in the registry record.
Primary question
The stated primary endpoint is boceprevir area under the concentration-time curve when boceprevir is taken alone. The investigators’ stated expectations were that boceprevir concentrations would be reduced with etravirine and etravirine concentrations increased with boceprevir. These are hypotheses, not reported findings. The registry record does not report the endpoint estimate or an interaction result.
3. Trial Design
This was a randomized, unmasked crossover study, recorded as completed. The registry record lists enrollment of 26 and identifies the participants as volunteers negative for HIV and hepatitis C. The study was sponsored by the University of Colorado, Denver, and its phase is listed as NA. The record gives a start of 2011-08 and primary completion of 2011-12.
Participants were assigned to one of six sequences. Each sequence arranged the same three medication conditions in a different order: boceprevir alone, etravirine alone, and both drugs together. The listed orders include each condition first, with alternative orders for the remaining conditions. This setup makes the study a crossover rather than a parallel-group design: participants are intended to receive multiple conditions in sequence rather than remain in a single treatment group.
In general, a crossover design can support comparisons within the same participant, which may reduce the influence of stable differences between participants. That benefit depends on appropriate conduct and analysis, including handling of sequence and period effects. The registry record does not report whether a washout interval was used, how long each medication condition lasted, or the planned statistical model. It also does not report the number completing every sequence.
The primary endpoint is boceprevir AUC when administered alone, measured from pre-dose and post-dose time points on day 11-14. The listed timeframe includes pre-dose and 1, 2, 3, 4, 5, 6, and 8 hours post dose. The registry record names 12 outcome measures, but lists 0 analyses. It therefore does not report a complete account of how the randomized sequences were analyzed or how the main interaction question was tested.
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: There were 8 subjects that were excluded from trial before assignment to groups; 5 due to personal reasons, 2 due to elevated bilirubin, and 1 due to elevated serum creatinine.
Overall Study
| Stage | Sequence 1a | Sequence 1b | Sequence 2a | Sequence 2b | Sequence 3a | Sequence 3b |
|---|---|---|---|---|---|---|
| STARTED | 4 | 3 | 4 | 6 | 3 | 6 |
| Received Boceprevir | 4 | 3 | 3 | 5 | 2 | 4 |
| Received Etravirine | 4 | 2 | 4 | 6 | 2 | 4 |
| Received Combination | 4 | 3 | 3 | 6 | 3 | 6 |
| COMPLETED | 4 | 2 | 3 | 5 | 2 | 4 |
| NOT COMPLETED | 0 | 1 | 1 | 1 | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: The number of participants was based on the number of subjects that completed all three sequences of medication.
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Sequence 1a | Sequence 1b | Sequence 2a | Sequence 2b | Sequence 3a | Sequence 3b |
|---|---|---|---|---|---|---|---|
| Participants analysed | 4 | 3 | 4 | 6 | 3 | 6 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 3 | 3 | 6 | 3 | 6 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age Continuous | years | 42.7 (SD 13.4) | 35.6 (SD 8.0) | 33.3 (SD 9.8) | 25.9 (SD 3.8) | 42.7 (SD 16.8) | 32.4 (SD 9.3) |
| Sex: Female, Male: Female | Participants | 1 | 2 | 0 | 3 | 2 | 6 |
| Sex: Female, Male: Male | Participants | 3 | 1 | 4 | 3 | 1 | 0 |
| Region of Enrollment: United States | participants | 4 | 3 | 4 | 6 | 3 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Boceprevir AUC Pharmacokinetics, measured over Pre-dose and, 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng*hr/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is boceprevir area under the concentration-time curve, or AUC, when boceprevir is administered alone. The record describes the measurement as a geometric mean, with geometric coefficient of variation as the measure of dispersion. Concentrations were scheduled for assessment pre-dose and at 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14.
In general, AUC represents overall drug exposure across a defined measurement interval, rather than concentration at a single time point. It is used in pharmacokinetic studies because a drug’s concentration changes over time, and a summary of the curve can characterize exposure across that interval. AUC is not itself a clinical outcome such as symptom change or disease progression.
A geometric mean is a summary suited to measurements that are positive and may be distributed asymmetrically. The geometric coefficient of variation describes relative spread on a multiplicative scale; it is not the same as a standard deviation in the original measurement units. These are general interpretations of the stated statistical summaries. The registry record does not report the observed AUC, the geometric coefficient of variation, or a confidence interval.
The primary endpoint description concerns boceprevir alone. It does not, by itself, report the difference between boceprevir alone and boceprevir taken with etravirine. That comparison, the method for estimating it, and any decision criterion for interpreting it are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s design, stated pharmacokinetic question, and planned primary measurement, but it does not report the primary outcome result. No boceprevir AUC estimate, geometric coefficient of variation, treatment contrast, or confidence interval is reported. As a result, the magnitude and precision of boceprevir exposure under the listed conditions cannot be assessed from this record.
The investigators’ brief summary states expectations about drug concentrations: boceprevir concentrations were expected to be reduced when given with etravirine, and etravirine concentrations were expected to be increased when given with boceprevir. The summary also states an expectation that the drugs would be safe when administered alone or together. These are the investigators’ beliefs recorded as study rationale, not outcome findings. They should not be read as evidence that either concentration changed or that a safety conclusion was demonstrated.
The randomized crossover arrangement includes medication-alone and combined conditions in different orders. In general, comparing measurements from the same participant across conditions can help control for stable individual differences. However, interpreting such a comparison requires the actual estimates and a suitable analysis that accounts for the crossover structure. The registry record lists 0 analyses and does not report the statistical model, sequence or period handling, or a formal contrast between combined use and either drug alone.
The primary endpoint is specifically boceprevir AUC when taken alone. It is not described as the direct coadministration contrast. Although the broader study rationale concerns possible drug-drug interactions, a stated rationale does not establish that the interaction was measured, estimated, or statistically tested as a primary comparison. The record does not report a bioequivalence margin, equivalence criterion, or confidence interval against such a criterion.
The registry lists 26 enrolled participants, but the primary outcome description says the number was based on participants who completed all three sequences. The number completing all sequences and the number contributing to each outcome are not reported in the registry record. Therefore, the enrollment count alone cannot establish the analyzed sample size or the completeness of the endpoint data.
Safety information is recorded separately by medication condition. Serious adverse events were reported for 0 of 21 participants at risk during boceprevir alone, 1 of 22 during etravirine alone, and 5 of 25 during coadministration. These are descriptive counts, and the record does not provide a comparative safety analysis or explain how repeated exposure in the crossover design was handled. The posted counts do not resolve the pharmacokinetic question.
Overall, the record supports a description of the intended study question and design, not an estimate of the interaction. Without endpoint results, uncertainty estimates, and a stated analysis, neither the direction nor size nor precision of any pharmacokinetic difference can be determined from the registry record.
9. Statistical Methods Explained
What does a crossover design mean?
In a crossover study, participants receive more than one study condition in sequence. This record lists six randomized sequences involving boceprevir alone, etravirine alone, and both drugs together. Randomizing the order is intended, in general, to reduce the chance that sequence order is systematically tied to participant characteristics. The registry record does not describe the randomization procedure or the analysis used to account for sequence.
General: because the same participant can contribute measurements under multiple conditions, a crossover analysis can compare within-person responses. This may reduce variability due to stable characteristics that differ across people. It does not remove every source of bias or variability. Effects that change over time, the order of conditions, carryover from a prior condition, and incomplete participation can matter. The registry record does not report a washout interval, a carryover assessment, or how missing sequence data were handled.
What does AUC measure?
The stated endpoint is boceprevir area under the concentration-time curve when administered alone. In general, AUC summarizes exposure over a defined time interval by accounting for the concentration profile across time. The listed assessment schedule is pre-dose and 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14. The record does not report the observed concentrations or AUC value, nor does it specify the numerical integration method used to obtain AUC.
AUC differs from a single concentration measurement: a single time point describes concentration at that moment, while AUC is intended to characterize exposure across the specified interval. The chosen sampling schedule determines which parts of the profile are observed, and the method used to summarize those observations affects the estimate. These are general measurement considerations; the registry record does not provide additional operational detail about sampling or computation.
Why report a geometric mean and geometric coefficient of variation?
The primary endpoint is described using a geometric mean, with geometric coefficient of variation for dispersion. General: for positive measurements with multiplicative variation or a right-skewed distribution, geometric summaries can be more suitable than arithmetic summaries. A geometric mean is obtained on a logarithmic scale and then expressed on the original scale. A geometric coefficient of variation describes relative variability rather than spread in the original units.
These summaries do not replace an estimate of the treatment contrast. To assess whether coadministration is associated with a change, an analysis would need to estimate a contrast between relevant conditions and describe its uncertainty. In many pharmacokinetic comparisons, this involves a ratio-scale estimate, but the registry record does not state the planned contrast or analysis scale. No such estimate is reported.
What does randomization contribute?
The study is identified as randomized and unmasked. In general, random allocation can help balance known and unknown participant characteristics across assigned sequences, on average. In a crossover design, it also helps prevent assignment order from being chosen in a way that systematically favors a particular sequence. Randomization does not guarantee balance in a small study, and it does not address measurement or analysis choices after assignment.
Unmasked means the record does not identify masking. The registry lists masking as none. In general, lack of masking can affect expectations or behavior, although an objective pharmacokinetic measurement may be less susceptible to some forms of observer judgment than a subjective outcome. The record does not describe assay procedures, laboratory masking, or quality-control methods, so those details cannot be assessed.
What can a confidence interval tell a reader?
General: a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. Its width reflects both the variability in the data and the amount of information available, as well as the analysis assumptions. An interval around a treatment contrast would help readers assess which effect sizes are compatible with the observed data. No confidence interval is reported for the primary outcome or a coadministration contrast.
A p-value, if reported, would address compatibility of the data with a specified null hypothesis under the model assumptions; it would not state the probability that the null hypothesis is true, nor would it describe the size or practical importance of an effect. The registry record lists 0 analyses and reports no p-value for the primary pharmacokinetic question. No conclusion about statistical significance can be drawn from the record.
How should the sample-size information be read?
The primary outcome description says the number of participants was based on the number who completed all three medication sequences. The registry record does not report a numerical target, a sample-size justification, or the number who completed all sequences. It therefore does not establish whether the completed sample was sufficient for a particular precision or hypothesis test.
The record also states assumptions for a planning illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect set as a stated fraction of the observed effect. Those are planning assumptions, not the trial’s reported design justification. The available record does not report resulting sample-size counts. Any such planning illustration would not be observed power and would not replace the trial’s actual estimate and uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 12 outcome measures and 0 analyses. It identifies boceprevir AUC when administered alone as the primary endpoint, but does not report a statistical analysis plan, a hierarchy of outcomes, or a procedure for controlling multiplicity. It is therefore not possible to determine how multiple outcomes, time points, or potential comparisons were handled. The record does not report whether any interim analyses were planned or conducted.
The primary endpoint description says the participant count was based on completion of all three sequences. The number completing all sequences, the number with usable measurements for each outcome, and the analysis population are not reported in the registry record. No missing-data method, imputation method, or sensitivity analysis is described. The consequences of incomplete sequence data therefore cannot be evaluated.
General: missingness can affect an estimate when the availability of outcome data is related to participant characteristics, treatment condition, or the outcome itself. In a crossover study, incomplete participation may also mean that some participants contribute measurements for only part of the planned sequence. The appropriate analysis depends on the design and reasons for missingness; those details are not reported for this study.
The record does not report whether all randomized participants were included in an intention-to-treat analysis, whether a per-protocol population was defined, or how deviations from assigned sequence were handled. It also does not identify a prespecified model for the repeated measurements. Without these details and the outcome results, the robustness of any treatment comparison cannot be assessed.
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 |
|---|---|---|---|
| Boceprevir Alone | 0 | 21 | 0.0% |
| Etravirine Alone | 1 | 22 | 4.5% |
| Boceprevir Coadministered With Etravirine | 5 | 25 | 20.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Boceprevir Alone | 19 of 21 |
| Etravirine Alone | 11 of 22 |
| Boceprevir Coadministered With Etravirine | 21 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Boceprevir Alone | Etravirine Alone | Boceprevir Coadministered With Etravirine |
|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | 0 of 21 | 1 of 22 | 3 of 25 |
| Increased energy, anxiety, nervousness, insomnia | Nervous system disorders | 0 of 21 | 0 of 22 | 1 of 25 |
| Presumed Viral Illness | Gastrointestinal disorders | 0 of 21 | 0 of 22 | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Boceprevir Alone | Etravirine Alone | Boceprevir Coadministered With Etravirine |
|---|---|---|---|---|
| Altered Taste | Gastrointestinal disorders | 18 of 21 | 0 of 22 | 16 of 25 |
| Headache | General disorders | 4 of 21 | 5 of 22 | 4 of 25 |
| Nausea | Gastrointestinal disorders | 4 of 21 | 3 of 22 | 3 of 25 |
| Fatigue | General disorders | 3 of 21 | 1 of 22 | 3 of 25 |
| Hypokalemia | General disorders | 4 of 21 | 0 of 22 | 2 of 25 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 21 | 2 of 22 | 4 of 25 |
Serious events with the highest arm-level rate: rash (12.0%), increased energy, anxiety, nervousness, insomnia (4.0%), presumed viral illness (4.0%).
The registry record reports serious adverse events by medication condition. During boceprevir alone, 0 of 21 participants at risk had a serious adverse event; during etravirine alone, 1 of 22 did; and during boceprevir coadministered with etravirine, 5 of 25 did. These are counts from the posted results, not a randomized between-group comparison. The record does not report a comparative statistical analysis of these counts.
Other adverse events affected 19 of 21 participants during boceprevir alone, 11 of 22 during etravirine alone, and 21 of 25 during coadministration. In a crossover study, the same participant may contribute to more than one condition, so condition-specific counts should not be interpreted as independent groups without further information. The registry record does not report participant-level overlap or details of event timing and attribution.
The listed serious-event terms and percentages are Rash, 12.0%; Increased energy, anxiety, nervousness, insomnia, 4.0%; and Presumed Viral Illness, 4.0%. The record does not clarify the denominator or analytic basis for those percentages. Deaths are not reported in the registry record. These descriptive entries do not establish a causal relationship or comparative risk.
12. What the Result Does, and Does Not, Mean
This study record identifies a randomized crossover investigation of boceprevir and etravirine in volunteers negative for HIV and hepatitis C. Its central motivation was a possible drug-drug interaction, with the investigators expecting reduced boceprevir concentrations and increased etravirine concentrations during coadministration. The primary endpoint, however, is specifically boceprevir AUC when administered alone.
The record does not report the primary endpoint value, a coadministration estimate, or an uncertainty interval. It therefore does not show whether either drug’s concentration changed when the drugs were taken together. It also does not report a formal equivalence or bioequivalence criterion, despite the study title’s reference to bioequivalence. Without a prespecified decision margin and the relevant estimates, a conclusion about equivalence cannot be drawn from the registry record.
The safety entries describe serious and other adverse events by medication condition, but they are not accompanied by a comparative analysis. The crossover arrangement also means that condition-level event counts may include the same participant under different conditions. The record does not provide enough detail to interpret these counts as a causal comparison or to determine whether events were attributable to a particular medication.
General: an absent result is not evidence that there was no effect, and a study rationale is not a result. A conclusion about the size, direction, or precision of an interaction requires the observed measurements, a defined comparison, and an analysis that reflects the design. These elements are not reported for the primary pharmacokinetic question.
The record can therefore be used to understand the intended population, treatment conditions, sequence structure, and endpoint. It cannot establish whether coadministration changed exposure, whether any change was clinically important, or whether the treatments were equivalent. Those questions remain unresolved by the information reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it uses a randomized crossover design to study pharmacokinetic exposure under medication-alone and combined conditions. In general, within-participant comparisons can be efficient when measurements from the same person are correlated, because stable differences between participants may contribute less to the contrast. That potential advantage depends on complete and appropriately analyzed sequence data.
The sequence structure also raises methodological questions that matter for interpretation. Period effects, order effects, carryover, and incomplete participation can affect comparisons in a crossover study. The registry record lists six randomized sequences but does not describe a washout interval or the planned model for sequence and period. Without those details, it is not possible to determine how the design’s repeated observations were intended to be handled.
The endpoint choice illustrates the distinction between a pharmacokinetic summary and a comparative result. AUC summarizes exposure across a defined sampling interval, while the central interaction question requires a comparison of exposure across conditions. The record describes AUC for boceprevir alone but does not report the corresponding treatment contrast or its uncertainty.
Finally, the record distinguishes an investigator expectation from an empirical finding only if readers attend to the wording: the brief summary states beliefs about concentration changes and safety, whereas no primary outcome result is reported. The safety counts are also descriptive and arise from condition-specific observations in a crossover setting. These features make it important to separate the trial’s rationale, design, measured endpoint, and demonstrated result rather than treating them as interchangeable.
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 for interpretation is that the registry record does not report the primary outcome result. It gives no boceprevir AUC estimate, geometric coefficient of variation, confidence interval, or comparison between medication conditions. The main pharmacokinetic question therefore cannot be answered from the recorded results.
The primary endpoint is described as boceprevir AUC when administered alone, while the study rationale concerns concentration changes during coadministration. The registry record does not identify a primary interaction contrast, an equivalence margin, or a decision rule for bioequivalence. The relationship between the endpoint description and the broader interaction question is consequently unclear.
Important crossover details are not reported, including washout arrangements, handling of sequence and period, carryover assessment, and the model used for repeated measurements. The record lists enrollment of 26 but does not report the number completing all three sequences or the outcome-specific analysis populations. Missing-data procedures and sensitivity analyses are also not reported.
The record lists 12 outcome measures and 0 analyses. It does not describe a multiplicity strategy, interim analyses, or a statistical analysis plan. The listed safety counts are not accompanied by a comparative analysis, event timing, participant-level overlap, or a clear explanation of the percentages attached to serious-event terms. These omissions limit assessment of both the pharmacokinetic findings and the safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Potential for Drug-drug Interactions Between Boceprevir and Etravirine in HIV/Hepatitis C Virus Negative Volunteers — NCT01427504.
- Registry record last updated 2013-07-09; status last verified 2013-06.
- Results first posted 2013-07-09.
- 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.
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18. Record Summary
NCT01427504 is a completed, randomized, unmasked crossover study sponsored by the University of Colorado, Denver. It enrolled 26 HIV- and hepatitis C-negative volunteers and used six sequences of boceprevir alone, etravirine alone, and the drugs together. The record gives a start of 2011-08 and primary completion of 2011-12.
The primary endpoint is boceprevir AUC when administered alone, summarized as a geometric mean with geometric coefficient of variation. The scheduled timeframe is pre-dose and 1, 2, 3, 4, 5, 6, and 8 hours post dose on day 11-14. The registry record lists 12 outcome measures and 0 analyses, but does not report the primary endpoint result or a statistical comparison addressing the interaction hypothesis.
Serious and other adverse-event counts are reported by medication condition. The record does not report deaths, the number completing all sequences, or a comparative safety analysis. The stated concentration changes and safety expectations are hypotheses in the study rationale, not reported conclusions.