Pharmacokinetics of Voxilaprevir in Adults With Normal Renal Function and Severe Renal Impairment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Voxilaprevir in Adults With Normal Renal Function and Severe Renal Impairment (NCT02402452), a non-randomized phase 1 study. The primary outcome is Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast.

2. Clinical Question

The study’s stated objective was to evaluate pharmacokinetics, safety, and tolerability in participants with severe renal impairment and matched healthy controls. The primary endpoint concerns drug exposure over time, rather than a clinical outcome such as symptom improvement or prevention of disease. Serial blood concentration measurements after dosing were used to characterize the exposure measure. Safety was also assessed, including treatment-emergent adverse events and laboratory abnormalities as a secondary outcome.

The central interpretive question is whether the posted pharmacokinetic estimates indicate a difference between the renal-function groups and how precisely that difference is estimated. The registry record does not report the numerical AUClast estimates, confidence intervals, or a formal comparison between groups. Consequently, it does not support a quantitative conclusion about the size or precision of any group difference.

3. Trial Design

This was a Phase 1, open-label, parallel-group, nonrandomized study of voxilaprevir. The registry lists an enrollment of 20 and describes two groups: participants with severe renal impairment and participants with normal renal function. Both groups received a single dose on Day 1. There was no masking. The record identifies Gilead Sciences as the sponsor and lists the study as completed.

The parallel-group structure means participants belonged to a renal-function group rather than being assigned to different study treatments within a randomized comparison. The registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Thus, any observed group difference would be descriptive of these enrolled groups; it should not automatically be attributed to renal function alone. How the groups were matched, which characteristics were used for matching, and how remaining differences between groups were handled are not reported in the registry record.

The primary objective covered pharmacokinetics, safety, and tolerability. The primary outcome was AUClast, the area under the plasma concentration-versus-time curve from time zero to the last quantifiable concentration. Blood sampling was scheduled from predose through 120 hours postdose, with multiple postdose time points. The registry describes the primary outcome as unadjusted geometric means with 95% confidence intervals.

The registry lists treatment-emergent adverse events and laboratory abnormalities as a secondary outcome. It reports adverse-event counts for the two groups, but the detailed numerical results for the primary pharmacokinetic endpoint are not reported in the registry record. The protocol’s eligibility criteria, dose amount, sample-size justification, and detailed statistical plan are also not reported in the registry record. Completion status does not, by itself, establish that all planned analyses or data were reported.

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: 39 participants were screened.

Overall Study

Analysis population for the primary outcome, as defined in the registry: PK Analysis Set included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by the PK laboratory for the corresponding analyte.

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.

Population: Safety Analysis Set included all participants who took at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast, measured over 0 (predose ≤ 5 min) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose.

AUClast measures cumulative plasma drug exposure from time zero through the last concentration that can be quantified. It is derived from the concentration-versus-time profile, rather than from a single blood concentration. In this study, concentrations were collected at scheduled times after a single dose, allowing the area under the profile to represent exposure across the observed sampling period.

Pharmacokinetic measures such as AUClast are used to describe how much drug is present in the body over time. Comparing such measures between groups can help characterize whether exposure differs across participant characteristics, including renal function. That is a pharmacokinetic question; it is not, on its own, a measure of clinical benefit, harm, or treatment effectiveness.

The registry specifies a geometric mean and a 95% confidence interval for the endpoint and says the data are unadjusted. A geometric mean summarizes values on a multiplicative scale and is commonly used for pharmacokinetic measurements, which can be skewed. A confidence interval communicates the uncertainty around an estimate under the statistical method used. The numerical group estimates and their confidence intervals are not reported in the registry record, so the magnitude and precision of AUClast in either group cannot be assessed from the registry information available.

The sampling schedule extended from predose to 120 hours after dosing. AUClast ends at the last quantifiable concentration, so it does not necessarily represent exposure over an unlimited period. The registry definition does not give the numerical concentration data, explain how values below quantification were handled, or provide an estimate for any later exposure beyond the observed and quantifiable profile. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does AUClast measure?

AUClast is the area under the plasma concentration-versus-time curve from time zero to the last quantifiable concentration. In general, an area-under-the-curve measure combines concentration information across time, rather than representing drug concentration at only one sampling point. This makes it a summary of observed exposure over the measured profile. It remains bounded by the sampling and quantification of the concentrations: the registry definition does not make it a measure of all exposure after the final quantifiable sample.

The study collected samples at predose and at scheduled postdose times through 120 hours. Repeated observations contribute to the profile from which the endpoint is derived. The exact concentration data and the numerical AUClast results are not reported in the registry record. Nor does the record describe the handling of concentrations that could not be quantified or the details of the calculation beyond the endpoint definition.

Why report geometric means?

The registry says the primary outcome is presented as an unadjusted geometric mean. In general, a geometric mean summarizes data on a multiplicative scale and is often used for pharmacokinetic measurements because such measurements may have a skewed distribution. It is distinct from an arithmetic mean, which summarizes values on an additive scale. The choice of summary affects how the central tendency is described; it does not itself show whether groups differ.

“Unadjusted” means the reported summary is not described as controlling for other variables. The registry does not report an adjusted model for AUClast. In a nonrandomized comparison, unadjusted summaries can reflect both the characteristic of interest and other differences between groups. The registry’s warning that these arms are not a like-for-like control comparison is therefore important when interpreting any group contrast.

What does a 95% confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimate under the method used to construct it. It gives a range of values compatible with the data and method, rather than a guarantee that the true value lies within a particular interval. An interval’s width is influenced by variation and the information available. The registry specifies a 95% confidence interval for the geometric mean, but the interval limits are not reported in the registry record. Its precision therefore cannot be judged from the record.

A confidence interval for each group’s estimate would describe uncertainty in those summaries. A direct comparison would require an appropriate contrast and its uncertainty, or another clearly specified inferential procedure. Separate group intervals alone are not a substitute for a reported group contrast. The registry record does not give a numerical comparative estimate, a test result, or a detailed procedure for comparing the groups.

Why does the nonrandomized design matter?

In general, random allocation helps balance measured and unmeasured characteristics across treatment groups, on average. This study did not use random allocation: renal-function groups were compared in a parallel design, and the registry explicitly says the arms are not a like-for-like control comparison. That does not prevent descriptive pharmacokinetic summaries, but it limits causal interpretation. Differences in participant characteristics or other factors could accompany the renal-function grouping. The matching details and any methods to address such differences are not reported in the registry record.

The study was open-label and had no masking. For an objective concentration-based endpoint, awareness of group assignment may be less directly relevant to the measurement than it would be for a subjective outcome, but it does not remove other design limitations. The registry does not report laboratory blinding or procedures for independent review, so those details should not be assumed.

What can be concluded from the posted analysis information?

The record identifies the endpoint, its unit, summary measure, confidence-interval type, time frame, and a definition of the pharmacokinetic analysis set. It does not report the endpoint’s numerical results or a detailed statistical analysis plan. In general, an analysis plan would clarify such matters as the comparison method, handling of missing or nonquantifiable observations, and any adjustment for covariates. Those methods are not reported in the registry record. The record’s statement that the estimates are unadjusted should not be expanded into assumptions about other unreported analytical choices.

Pharmacokinetic data may show variability across participants. In general, over-dispersion means that observed variation is greater than a model or simple distributional assumption would anticipate. It can affect standard errors and uncertainty estimates if not adequately represented by the chosen method. The registry record does not report a dispersion model or diagnostic assessment, so no claim can be made about whether over-dispersion was assessed or how it was handled.

Finally, the study is Phase 1 and uses a single-dose design. These features describe the study’s scope, not the results. They do not, on their own, determine the quality or precision of the endpoint estimates. Because the primary numerical findings are absent from the registry information, the statistical interpretation must remain limited to the stated design, endpoint definition, and analysis summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and three analyses. It identifies AUClast as the primary outcome and lists the percentage of participants who experienced treatment-emergent adverse events and laboratory abnormalities as a secondary outcome. The registry record does not report whether a multiplicity adjustment was planned or used, how the analyses correspond to the outcome measures, or whether any analyses were designated exploratory. Without that information, the risk of chance findings across multiple analyses cannot be assessed from the record.

The definition of the pharmacokinetic analysis set includes enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by the PK laboratory for the corresponding analyte. This specifies an inclusion criterion for the PK analysis population. The record does not report how many participants met that definition, whether all enrolled participants contributed to each analysis, or whether the outcome-specific analysis populations differed.

Missing-data handling is not reported in the registry record. In general, missing observations can affect an estimate when the probability of missingness is related to participant characteristics or outcomes. Pharmacokinetic analyses may also require rules for concentrations that are absent or not quantifiable. The registry record does not describe such rules or report the extent of missing concentration data. It is therefore not possible to assess their influence on the endpoint estimates.

The record also does not report a statistical analysis plan, an interim-analysis plan, or a sample-size justification. These absences do not establish that such procedures were or were not used; they mean the details are not reported in the registry record. The numerical primary-endpoint results are also not reported, which further limits assessment of precision, multiplicity, and robustness.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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 serious adverse-event counts separately for the two renal-function groups. Among 10 participants at risk in the severe renal impairment group, the serious adverse-event count was 0; among 10 at risk in the normal renal function group, it was also 0. The registry lists no serious adverse-event terms. These are observed counts in this study, not proof that serious events cannot occur.

For other adverse events, the record gives a count of 2 among 10 at risk in the severe renal impairment group and a count of 5 among 10 at risk in the normal renal function group. These counts should be read as descriptive registry figures. The record does not provide event terms, severity details, timing, participant-level overlap, or a statistical comparison for these counts. It also does not establish that the difference between the counts is meaningful.

The secondary outcome is described as the percentage of participants who experienced treatment-emergent adverse events and laboratory abnormalities. The available safety figures do not include detailed laboratory-abnormality results. They should not be interpreted as a comprehensive account of all safety findings or as a comparison adjusted for differences between the nonrandomized groups.

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

This study addresses a pharmacokinetic question: how voxilaprevir exposure, summarized by AUClast, was characterized in participants with severe renal impairment and in participants with normal renal function after a single dose. The registry provides the endpoint definition, the planned sampling period, and the type of summary intended. It does not report the numerical AUClast estimates or their 95% confidence intervals. The size, direction, and precision of any exposure difference therefore cannot be determined from the registry record.

The design also limits what a comparison could mean. The study was nonrandomized and open-label, and the registry cautions that the groups are not a like-for-like control comparison. Any difference in observed summaries could be associated with factors other than renal-function status. The record does not describe the matching procedures or a covariate-adjusted analysis. A descriptive group contrast, if available, would not by itself establish a causal effect of renal impairment.

The safety counts show no recorded serious adverse events in either group in the posted figures, alongside other adverse-event counts in both groups. Such counts are informative descriptions of what was recorded during the study, but they do not establish that a treatment is safe or unsafe, and they do not demonstrate equivalence between groups. Detailed event terms and laboratory-abnormality results are not reported in the registry record.

The study’s Phase 1, single-dose design defines a focused pharmacokinetic and safety assessment. It does not answer broader questions about clinical outcomes or repeated dosing. The registry’s completed status does not fill in the missing numerical endpoint results. The sound interpretation is therefore limited: the study was designed to characterize single-dose pharmacokinetics and safety across renal-function groups, but the registry information does not allow a quantitative assessment of the primary endpoint.

13. Why This Trial Matters Statistically

Renal function can be an important characteristic when describing drug exposure, so a study comparing pharmacokinetic profiles across renal-function groups addresses a distinct methodological question. AUClast is a useful summary of the measured concentration-time profile because it represents exposure across the observation period rather than a concentration at one time point. The registry’s definition makes clear what the primary measure is intended to capture.

The study also illustrates why design and results must be read together. A parallel-group comparison can describe differences between groups, but nonrandom allocation means group differences may reflect more than the renal-function category. The registry explicitly warns against treating the arms as a like-for-like control comparison. Matching is mentioned in the study objective, but the variables and methods are not reported in the registry record. The limitation is relevant to interpretation even if detailed endpoint estimates were available.

Reporting geometric means and confidence intervals is a recognizable approach for pharmacokinetic outcomes. In general, the summary scale can suit positively skewed measurements, while the interval communicates uncertainty. Yet naming the method is not enough to assess a result: readers need the estimates, interval limits, and a clear account of any between-group comparison. Those numerical AUClast results are not reported in the registry record.

The record therefore highlights a broader statistical principle: a defined endpoint and completed study do not guarantee that the posted information supports an estimate of effect or precision. Safety counts can be described, but they do not replace the primary pharmacokinetic results. For this study, the design, endpoint definition, and safety figures can be characterized; the primary quantitative comparison cannot be evaluated from the registry record.

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 primary limitation for interpretation is that the registry record does not report the numerical AUClast estimates or their 95% confidence intervals. Without those values, neither exposure in each group nor the precision of the summaries can be assessed. A numerical between-group comparison is also not reported in the registry record.

The groups were nonrandomized, and the registry cautions that they are not a like-for-like control comparison. Although the study objective refers to matched healthy controls, the matching variables and procedures are not reported in the registry record. No adjusted comparison is described. This leaves uncertainty about how much any group difference could reflect characteristics other than renal function.

The record does not report the dose amount, detailed eligibility criteria, sample-size justification, or full statistical analysis plan. It does not describe missing-data or nonquantifiable-concentration handling, multiplicity procedures, or interim analyses. These omissions prevent evaluation of those aspects; they should not be taken as evidence that a particular method was or was not used.

The registry identifies a PK analysis-set definition but does not report how many participants met it or whether all participants contributed to each endpoint. Safety reporting is also limited: the listed counts do not include detailed event terms or laboratory-abnormality results, and no comparative safety analysis is reported. Finally, the single-dose Phase 1 study design addresses a focused pharmacokinetic assessment and does not, by itself, describe outcomes under other dosing conditions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetics of Voxilaprevir in Adults With Normal Renal Function and Severe Renal Impairment — NCT02402452.
• Registry record last updated 2020-03-20; status last verified 2020-03.
• Results first posted 2020-03-20.
• 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.

18. Record Summary

NCT02402452 is a completed Phase 1, open-label, nonrandomized, parallel-group study sponsored by Gilead Sciences. It enrolled 20 participants and evaluated a single dose of voxilaprevir in groups with severe renal impairment and normal renal function. The primary endpoint was AUClast, summarized as an unadjusted geometric mean with a 95% confidence interval. The PK analysis-set definition required at least 1 dose and at least 1 nonmissing postdose concentration.

The registry record reports zero serious adverse events among 10 at risk in each group, and other adverse-event counts of 2 and 5, respectively. It does not report the numerical primary pharmacokinetic estimates or their confidence intervals. The record cautions that the nonrandomized groups are not a like-for-like control comparison, and it does not report detailed matching procedures or a full statistical plan.