Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment (NCT02002767), a non-randomized phase 1 study. The primary outcome is Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast.

2. Clinical Question

3. Trial Design

This was a completed Phase 1, open-label, non-randomized, parallel-group, single-dose study of velpatasvir. It enrolled 19 participants in total. The two groups were participants with severe renal impairment and participants with normal renal function; both groups received velpatasvir. The normal-function group was described as a control group for the pharmacokinetic assessment.

The registry record lists the study start as 2013-12-16 and the primary completion as 2014-06-09. The sponsor was Gilead Sciences. Allocation was non-randomized, and masking was absent. Those design features matter when interpreting comparisons: the groups were not created by random assignment, so observed group differences cannot be attributed solely to renal-function status on the basis of randomization. The record does not describe the matching procedure or provide the characteristics used to assess comparability between groups.

The primary outcome was the mean AUClast for velpatasvir, with standard deviation as the stated measure of dispersion. Blood sampling was scheduled from pre-dose through 120 hours post-dose on Day 1. The outcome’s analysis population was described as participants who were enrolled and treated and had evaluable velpatasvir pharmacokinetic profiles. The number in that analysis population is not reported in the registry record.

Listed secondary outcomes included the percentage of participants experiencing treatment-emergent adverse events, the percentage experiencing treatment-emergent laboratory abnormalities, and percentage protein binding of velpatasvir. The record lists 6 outcome measures and 3 analyses, but the available results do not give the primary pharmacokinetic group summaries. Details of the protocol, dose amount, matching procedure, and statistical analysis plan are not reported in the registry record.

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: 46 participants were screened.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The PK analysis set included all enrolled and treated participants who have evaluable PK profiles for velpatasvir.

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: The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast, measured over Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1.

The primary endpoint was the mean AUClast, a pharmacokinetic measure of velpatasvir exposure. It represents the area under the plasma concentration-versus-time curve from time zero through the last concentration that could be quantified. The registry record gives the unit as h*ng/mL and specifies standard deviation as the dispersion measure. Samples were scheduled at pre-dose and at multiple post-dose times through 120 hours post-dose on Day 1.

In general, an area-under-the-curve measure combines concentration information across the sampling period rather than describing concentration at only a single time. That makes it useful for characterizing overall measured drug exposure over the specified interval. AUClast ends at the last quantifiable concentration, so it is tied to the observed sampling and quantification window rather than necessarily representing exposure over an unlimited period.

The endpoint was intended to compare velpatasvir pharmacokinetics between the severe-impairment group and the normal-function group after a single dose. The registry record specifies a mean and standard deviation but does not provide the group values, an estimate of the between-group contrast, or a confidence interval. Consequently, the endpoint definition is available, but the magnitude and precision of the observed pharmacokinetic comparison are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that were actually used for the primary comparison are not reported in the registry record. The record identifies the primary measure as mean AUClast and its dispersion as standard deviation, but it does not state a test, model, adjustment strategy, confidence-interval method, or decision threshold. The explanations below describe general statistical concepts and should not be read as a description of methods confirmed for this study.

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, pharmacokinetic sampling produces a sequence of concentration observations after dosing. An area-under-the-curve summary integrates those observations across time, providing a measure of exposure over the observed interval. Because the endpoint ends at the last quantifiable concentration, the summary depends on the available sampling and on which concentration observations can be quantified.

The registry record gives h*ng/mL as the unit and describes the primary result as a mean with standard deviation. A mean is a measure of the center of a set of observed values. A standard deviation describes how much individual values vary around that mean. Neither measure alone gives the uncertainty in a comparison between groups: the mean is a group summary, and the standard deviation describes participant-level spread.

How should a group comparison be read?

In general, a comparison of group means starts with the mean AUClast in each group and an estimate of the contrast between them. The interpretation depends on the direction and size of that contrast, as well as its uncertainty. A confidence interval is a range of values compatible with the observed data under the method used. A narrow interval indicates greater precision than a wide interval, while an interval that spans substantially different possible contrasts leaves greater uncertainty about the magnitude of the difference.

The registry record does not report either group’s AUClast mean or standard deviation, nor a contrast or confidence interval. No inferential result for the primary endpoint can therefore be described. A p-value, if one had been reported, would address compatibility of the data with a specified null hypothesis under the analysis assumptions; it would not by itself measure the size or practical importance of a difference. No primary p-value is reported in the registry record.

Why does allocation matter?

The study was non-randomized and parallel-group. In general, random allocation can help balance measured and unmeasured participant characteristics between treatment groups. That protection does not apply in the same way when groups are formed by participant characteristics rather than random assignment. Here, the comparison was between renal-function groups, and both groups received velpatasvir. The record describes the normal-function participants as matched healthy controls, but the matching variables and procedure are not reported.

As a general principle, a non-randomized comparison can be affected by differences between groups other than the defining renal-function category. Statistical adjustment can sometimes account for measured differences, but it cannot automatically address unmeasured factors. The registry record does not report whether adjustment was performed or what covariates, if any, were considered. It is therefore not possible to assess the adequacy of any adjustment from the available information.

What does the sampling schedule contribute?

The record specifies pre-dose sampling and post-dose sampling through 120 hours on Day 1. In general, repeated sampling helps characterize the concentration-time profile used to derive pharmacokinetic summaries. The timing of samples matters because the summary is based on observed concentrations over time. The registry record identifies the planned sampling times but does not provide the concentration data, the number of evaluable profiles, or details of how missing or unquantifiable samples were handled.

For a continuous endpoint such as AUClast, individual observations can vary substantially. In general, unusually high or low values may influence a mean, and the distribution of values can affect how well a statistical model’s assumptions fit. The record does not describe the distribution of AUClast, any transformations, or diagnostic checks. No distributional or model assumption should be inferred from the reported endpoint description alone.

What do the planning assumptions mean?

The registry record includes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such an illustration is a planning exercise, not a report of the trial’s original design justification and not observed power. The record does not report a trial-specific sample-size justification. No planning sample-size values are included in the registry entries, so none can be stated.

In general, planning calculations depend on assumptions about the effect to be detected, variability, allocation, and the statistical method. A planning illustration based on an observed effect is conditional on that effect and should not be interpreted as evidence that a study was adequately powered. The trial’s enrollment of 19 participants is an observed enrollment fact; it does not by itself establish the precision of the primary comparison.

Finally, the record lists 6 outcome measures and 3 analyses. Those counts do not reveal how the analyses were selected, whether multiple comparisons were planned, or how multiplicity was handled. The statistical analysis plan, interim analyses, and multiplicity procedures 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("Normal Renal Function", "Severe Renal Impairment")
n   <- c(9, 10)
m   <- c(5597.8, 7971.7)
sp  <- c(1749.18, 2531.09)
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  Normal Renal Function  9  5597.800  1749.180  4253.261  6942.339
CARM  Severe Renal Impairment  10  7971.700  2531.090  6161.067  9782.333

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 3 analyses. It names secondary outcomes that include treatment-emergent adverse events, treatment-emergent laboratory abnormalities, and percentage protein binding of velpatasvir. The available information does not identify all analysis hypotheses, specify a hierarchy among outcomes, or describe whether any multiplicity adjustment was planned or used. The procedure for handling multiple comparisons is not reported in the registry record.

In general, testing several hypotheses can increase the chance of obtaining an apparently unusual result by chance if each test is interpreted independently. A prespecified hierarchy or multiplicity adjustment can address that issue, but neither should be assumed without documentation. The number of listed outcomes and analyses alone does not establish what inferential approach was taken.

The primary pharmacokinetic analysis population was defined as enrolled and treated participants with evaluable velpatasvir pharmacokinetic profiles. The number meeting that definition is not reported in the registry record. The safety results give group-specific participants at risk, but those denominators do not establish how many participants had evaluable data for every other outcome.

The record does not describe missing pharmacokinetic samples, incomplete profiles, missing laboratory results, exclusions from analysis, or methods for handling missing data. It also does not report whether any imputation was performed. These omissions limit assessment of how the analyzed populations relate to all enrolled participants. Interim analyses and any associated decision rules are not reported in the registry record.

12. 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 posted safety counts distinguish serious adverse events, other adverse events, and deaths for the two renal-function groups. In the normal-renal-function group, 0 of 9 participants were listed with a serious adverse event, 0 of 9 with another adverse event, and 0 deaths. In the severe-renal-impairment group, 0 of 10 were listed with a serious adverse event, 2 of 10 with another adverse event, and 0 deaths.

These figures are descriptive counts for the participants at risk in the posted results. They do not provide event-level detail for the two other adverse events, and the record lists no top serious-event terms. The registry record does not report further details about event timing, severity for non-serious events, relatedness, or how these counts were classified beyond the outcome labels.

In general, a zero count in a study group means that no event in that category was recorded among the participants at risk; it does not establish that an event cannot occur. These safety counts also do not answer the primary pharmacokinetic question. The small group denominators and non-randomized design mean the descriptive counts should not be treated as a precise comparative safety estimate.

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

The record establishes that the study was designed to evaluate single-dose velpatasvir pharmacokinetics in participants with severe renal impairment, using participants with normal renal function as a control group. Its primary endpoint was mean AUClast, defined as the area under the plasma concentration-versus-time curve through the last quantifiable concentration. The record also describes the sampling schedule and identifies standard deviation as the dispersion measure.

What the record does not establish is the observed primary result. It does not report the AUClast means or standard deviations by group, a between-group estimate, or a confidence interval. Without those values, readers cannot determine the magnitude or precision of the observed pharmacokinetic comparison from the registry record. The available information also does not report a primary hypothesis test or p-value.

The study’s non-randomized allocation means that the renal-function groups were not formed by random assignment. The normal-function group was described as matched, but matching details are not reported. In general, this design can describe a comparison between the enrolled groups, but it does not by itself ensure that all other participant characteristics are balanced.

The safety results report no serious adverse events and no deaths in either group, with other adverse events recorded for 0 of 9 participants with normal renal function and 2 of 10 with severe renal impairment. These are descriptive registry counts, not a substitute for the missing primary pharmacokinetic results or a definitive assessment of comparative risk.

The study therefore documents a focused pharmacokinetic question, a single-dose parallel-group design, and limited safety counts. It does not, in the information available, provide enough numerical primary-outcome results to quantify the exposure comparison or its uncertainty. No conclusion about a treatment effect or clinical use follows from the design description alone.

14. Why This Trial Matters Statistically

This study is statistically notable because it separates a pharmacokinetic question from a treatment-effect question. Both renal-function groups received a single dose of velpatasvir, and the principal comparison concerned AUClast between participants with severe renal impairment and participants with normal renal function. The design therefore aimed to characterize exposure across renal-function groups rather than compare velpatasvir with a different intervention.

The parallel-group structure makes clear which groups were compared, while the non-randomized allocation is important for interpretation. In general, when participants enter groups based on an existing characteristic, group differences may reflect other characteristics as well. The registry record describes the normal-function participants as matched controls, but does not report how matching was done. This makes the design description useful, while leaving important comparability details unavailable.

The endpoint also illustrates why an analysis needs more than a named measure. AUClast is defined, its unit is stated, and the record gives the sampling window and intended summary as mean with standard deviation. Yet the numerical group summaries and a comparative estimate are not reported. Without those results, neither the size of the observed contrast nor its statistical precision can be evaluated.

The record also illustrates the distinction between descriptive safety counts and a complete inferential assessment. The listed adverse-event counts give a limited account of events among participants at risk, but do not provide detailed event terms or a precise comparative estimate. For statistical interpretation, design, endpoint definition, analysis population, numerical results, and uncertainty all contribute; some of these elements are available, while others are not reported in the registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the study’s main question is that the registry record does not report AUClast results. Group means, standard deviations, the between-group contrast, and its confidence interval are absent from the available information. As a result, the magnitude and precision of the primary comparison cannot be assessed.

The study was non-randomized and open-label. The groups were defined by renal-function status, and the record describes the normal-function group as matched controls. Matching criteria and implementation are not reported. The record also does not provide participant characteristics that would allow readers to evaluate the similarity of the groups or determine whether an adjusted analysis addressed potential differences.

Although 19 participants were enrolled, the number in the defined pharmacokinetic analysis population is not reported. The record does not explain whether all enrolled participants were treated, had evaluable profiles, or contributed to the primary analysis. It also does not describe missing or unquantifiable samples, exclusions, or missing-data handling.

Further limitations of the available record include absent details about the dose amount, the protocol, the statistical analysis plan, interim analyses, and multiplicity procedures. The listed outcome and analysis counts do not clarify which comparisons were prespecified or how they were interpreted. Safety information is also limited to group counts; detailed terms for other adverse events and broader event-level context are not reported. These gaps restrict assessment of both the primary analysis and the completeness of the posted results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment — NCT02002767.
• Registry record last updated 2020-11-16; status last verified 2020-10.
• Results first posted 2020-11-16.
• 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

NCT02002767 was a completed Phase 1, open-label, non-randomized, parallel-group, single-dose study sponsored by Gilead Sciences. It enrolled 19 participants with normal renal function or severe renal impairment, and both groups received velpatasvir. The primary objective was to evaluate single-dose velpatasvir pharmacokinetics in severe renal impairment using matched healthy participants as a control group.

The primary endpoint was mean AUClast in h*ng/mL, with standard deviation specified as the dispersion measure. The pharmacokinetic analysis population was defined as enrolled and treated participants with evaluable profiles. Numerical AUClast results and the size and precision of the group comparison are not reported in the registry record. Safety results list no serious adverse events and no deaths in either group; other adverse events were recorded for 0 of 9 participants with normal renal function and 2 of 10 with severe renal impairment.