Safety, Tolerability, and Pharmacokinetic of Single Dose of Pitavastatin 4 mg in Severe Renal Patients Versus Healthy Adult Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Pharmacokinetic of Single Dose of Pitavastatin 4 mg in Severe Renal Patients Versus Healthy Adult Volunteers (NCT01043094), a non-randomized phase 4 study. The primary outcome is Area Under the Curve From 0 to Tau (AUC 0-t (ng*h/mL)).

2. Clinical Question

This study addressed a pharmacokinetic comparison: whether measured pitavastatin exposure after a single dose differed between the two defined groups. The primary outcome was area under the curve from 0 to tau, reported in nanogram hour per milliliter. The registry describes this as the area under the curve from start to elimination for pitavastatin and gives a 48-hour timeframe.

The registry summary states that 16 participants were planned, with 8 in each group. It also describes an intention to make the groups comparable in age, gender, and body mass index using ranges based on pooled demographic data from the renally impaired participants. That intention does not establish that the groups achieved the specified demographic comparability; achieved characteristics are not reported in the registry record.

The comparison is observational with respect to group membership: renal status defined the groups, and allocation was non-randomized. Accordingly, the question is about the observed pharmacokinetic profiles in these groups, not the effect of randomly assigning participants to renal impairment or health status. The posted results do not provide the primary endpoint values or an estimated group contrast. No conclusion about the direction, size, or precision of a pharmacokinetic difference can be drawn from the registry record alone.

3. Trial Design

The registry identifies this as a completed Phase 4 study with a non-randomized, open-label, parallel-group design. The stated study period for each participant was one period, and the intervention was a single oral dose of pitavastatin 4 mg. The record lists a planned enrollment of 16; the study summary specifies 8 planned participants in each group. The registry lists a start date of 2009-12 and a primary completion date of 2010-04.

The groups were defined by renal status. One group comprised adults with severe renal impairment, described as a GFR of 15 to 29 mL/min/1.73 m2, inclusive, who were not receiving hemodialysis. The other comprised healthy adults with a GFR of at least 90 mL/min/1.73 m2. Both groups received pitavastatin. This is therefore a comparison of pharmacokinetic observations across different populations, not a comparison of active treatment with placebo or with no treatment.

The study summary says the groups were to be comparable in age, gender, and body mass index. It specifies intended criteria for the group means and gender balance, but the achieved demographic values are not reported in the registry record. The record also does not report how participants were recruited or selected, how renal status was established beyond the listed GFR descriptions, or whether any departures from the planned group composition occurred.

Because allocation was not randomized and masking was absent, differences between groups may reflect characteristics associated with renal status as well as any pharmacokinetic differences. The stated comparability aims can be relevant to interpreting the design, but they do not remove the possibility of group differences in factors that were not measured, not reported, or not controlled in an analysis. No adjusted comparison or analysis plan is reported in the registry record.

The registry lists two outcome measures, including the primary AUC measure and a secondary measure concerning participants with treatment-emergent adverse events. It does not report results for the primary pharmacokinetic measure. The adverse-event record includes participant counts, discussed separately; it does not provide a detailed account of the full study procedures or analytic methods.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve From 0 to Tau (AUC 0-t (ng*h/mL)), measured over 48 hours.

The primary endpoint is area under the curve from 0 to tau, abbreviated in the record as AUC 0-t and measured in nanogram hour per milliliter. The listed timeframe is 48 hours, and the description calls it the area under the curve from start to elimination for pitavastatin. The endpoint is a continuous pharmacokinetic measure.

In general, an area-under-the-curve measure summarizes concentration over time: it reflects both the level of a substance and how that level changes across the measurement interval. This can provide an overall measure of drug exposure after dosing, rather than describing concentration at only one sampling time. The exact sampling schedule and endpoint calculation details are not reported in the registry record, so the precise implementation cannot be assessed from the record.

Comparing this measure between the severe renal impairment group and the healthy group can describe whether recorded pitavastatin exposure differed across those populations after the same stated dose. It is useful for a pharmacokinetic question because a group-level summary of exposure can be compared even when individual concentration profiles vary over time. That general rationale does not establish what the comparison found.

The registry record does not report the group means, standard deviations, estimated contrast, confidence interval, or significance test for the primary endpoint. Without those results, readers cannot determine the observed direction or size of the difference or how precisely it was estimated. The endpoint's name and unit describe what was intended to be measured, not the observed result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies AUC 0-t as the primary outcome and describes it as a mean with standard deviation. It is a continuous measure, with units of nanogram hour per milliliter, and a stated timeframe of 48 hours. The listed groups are parallel groups, but allocation is non-randomized and masking is absent.

What does an AUC measure?

In general, an area under a concentration-time curve aggregates information across the measurement interval. A concentration at one time point captures a moment; an area measure reflects concentration levels over time. The unit combines concentration and time, which is why the registry gives a unit of nanogram hour per milliliter. An AUC can be used to describe overall exposure in a pharmacokinetic study.

The registry describes the measure as extending from start to elimination, but it does not give the detailed sampling times, the calculation procedure, or additional rules for handling measurements. The term tau appears in the outcome name, but its operational definition is not reported in the registry record. The listed timeframe is 48 hours; that label alone does not establish every detail of how the endpoint was calculated.

What do the mean and standard deviation describe?

In general, a mean gives a group’s arithmetic average for a continuous measure. A standard deviation describes variation among individual values around that mean. Together, these summaries can convey the typical measured level and the spread of observations, but they do not show the full shape of the data or establish a group difference by themselves. Their interpretation also depends on the amount and pattern of available data.

The record identifies the intended summary form but does not report the actual group means or standard deviations for the primary outcome. It also does not report an estimated contrast, confidence interval, or test result. Consequently, readers cannot reconstruct or evaluate the primary comparison from the registry record.

Why does the non-randomized design matter?

In general, random allocation helps balance measured and unmeasured characteristics between treatment groups on average. Here, the groups were formed by renal status, and allocation is listed as non-randomized. The groups can differ for reasons associated with their defining population characteristics. The summary describes intended comparability in age, gender, and body mass index, but the achieved balance is not reported. Even if those characteristics were similar, other differences could remain.

For that reason, an observed difference in AUC would describe a contrast between these groups under the study conditions. It would not by itself demonstrate that renal status alone caused the contrast. An adjusted analysis could address some measured differences, but the registry does not report an analysis plan or adjusted endpoint results. The appropriate scope of interpretation is therefore descriptive unless additional design or analysis details are available.

What do confidence intervals and significance tests add?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrower interval indicates greater precision in that estimate, while a wider interval indicates less precision. A p-value summarizes how compatible data are with a specified null model under its assumptions; it is not a measure of the size or clinical importance of an effect. Neither type of statistic replaces inspection of the estimate itself.

No confidence interval or p-value for the primary endpoint is reported in the registry record. There is therefore no basis for describing the primary result as statistically significant or not statistically significant, or for judging the precision of an estimated contrast. The record also does not state the statistical test or model used.

How should planning illustrations be understood?

In general, a sample-size calculation uses assumptions about the effect to be detected, variability, significance level, allocation, and statistical method to illustrate the amount of information a future study might need. Such a calculation is a planning exercise, not a result observed in the participants and not a measure of observed power. It cannot establish that the completed study had adequate precision.

The registry’s planning description says its illustrations are based on the observed effect, use a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. The record does not report the observed primary effect or numerical planning outputs, so the implications of those illustrations cannot be evaluated. They should not be used as substitutes for the missing primary endpoint estimate or its uncertainty.

What role does over-dispersion have?

In general, over-dispersion occurs when variability in the data is greater than a statistical model expects. If a model assumes too little variability, standard errors may be too small and uncertainty may be understated. Model choice should reflect the outcome and its observed distribution. The primary endpoint is described as a continuous measure summarized by a mean and standard deviation; the registry does not report evidence of over-dispersion, a model that addresses it, or an analysis of the outcome distribution. It would not be appropriate to claim that over-dispersion was present or absent.

The record also does not state whether any transformations, covariate adjustments, or alternative analyses were used. With no reported endpoint summaries or analysis details, the available statistical interpretation is limited to the stated outcome definition and design. General statistical principles explain what such methods could contribute, but they do not fill in results absent from 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("Pitavastatin 4mg Renal Impaired", "Pitavastatin 4mg Healthy Subjects")
n   <- c(8, 8)
m   <- c(175, 145)
sp  <- c(39, 55)
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  Pitavastatin 4mg Renal Impaired  8  175.000  39.000  142.395  207.605
CARM  Pitavastatin 4mg Healthy Subjects  8  145.000  55.000  99.019  190.981

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pharmacokinetic outcome and a secondary outcome concerning the number of participants with treatment-emergent adverse events. It does not report a statistical plan for handling multiple outcomes or multiple comparisons. A multiplicity adjustment, a hierarchy among outcomes, or another strategy for controlling the interpretation of repeated tests is not reported in the registry record. Without the analysis details and results, the consequences of any multiplicity cannot be assessed.

The record does not describe how missing outcome measurements were handled, whether any observations were excluded from the primary analysis, or how incomplete follow-up was addressed. It also does not identify analysis populations for the primary endpoint, such as a population defined by treatment received or by availability of pharmacokinetic measurements. These matters are not reported in the registry record and should not be inferred from the planned group sizes.

The registry lists 16 participants as enrollment, while the study summary says 16 participants were planned, with 8 in each group. It does not state how many participants contributed usable primary endpoint data or whether enrollment and analysis populations were identical. No imputation method, missingness assessment, or sensitivity analysis is described.

In general, missing data can affect both the estimate and its precision, depending on why measurements are absent and how the analysis handles them. Multiplicity can also affect how strongly a result should be interpreted when several outcomes or tests are considered. These are general methodological concerns; the record does not provide the information needed to determine whether either issue altered this study’s results. No analysis results are reported in the registry record for the primary endpoint.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s serious-adverse-event entries show 0 affected participants among 8 at risk in the renal impairment group and 0 affected participants among 8 at risk in the healthy group. These are participant counts, not a detailed event narrative. The record does not list serious adverse-event terms.

For other adverse events, the record lists 3 affected participants among 8 at risk in the renal impairment group and 1 affected participant among 8 at risk in the healthy group. These are reported counts of participants, not counts of separate events; the registry does not provide the detail needed to establish how many events each participant experienced. It also does not provide event descriptions, timing, duration, or an inferential comparison of the groups.

The fields for deaths do not contain reported counts. Death figures are not reported in the registry record. The absence of a listed serious adverse event in these entries should be read narrowly as the recorded participant counts, not as proof that no other safety issue occurred or that the study could rule out uncommon harms. The study summary describes a single-dose study, and these registry entries alone do not establish safety beyond the reported observations.

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

The registry record establishes that a Phase 4, open-label, non-randomized study compared a single dose of pitavastatin 4 mg in adults with severe renal impairment who were not on hemodialysis and healthy adults. Its primary objective was a pharmacokinetic comparison using AUC 0-t over a 48-hour timeframe. The record does not include the group-level primary outcome values or a statistical comparison, so it does not reveal whether measured exposure was higher, lower, or similar between the groups.

The record does provide selected adverse-event counts: no participants with serious adverse events are recorded in either group, while other adverse events are recorded for 3 participants in the renal impairment group and 1 in the healthy group. The event details and analysis are absent, so these counts cannot establish a comparative safety profile or characterize the nature of the events. Death figures are not reported in the registry record.

The design also limits what any observed group contrast could mean. Since renal status defined group membership and allocation was non-randomized, a contrast would be observational rather than a randomized causal estimate. The study summary’s stated intention to match groups on age, gender, and body mass index does not document achieved balance or control for other differences. No adjusted results are reported.

These findings do not show that pitavastatin works or does not work, and the registry does not present an efficacy outcome. Nor does the missing primary result mean that there was no difference. It means that the primary comparison cannot be interpreted from the registry record. More generally, a study’s endpoint definition and design describe what was asked and how; they do not substitute for the observed estimate, its uncertainty, and the analysis details needed to assess it.

14. Why This Trial Matters Statistically

This study is statistically relevant because it asks a focused pharmacokinetic question across two populations defined by renal status, while making the design limitations visible. AUC is a continuous exposure measure that summarizes concentration over time, so the intended comparison differs from a simple assessment at one sampling moment. The registry identifies the measure, unit, and timeframe, allowing the endpoint’s purpose to be understood even though its results are absent.

The non-randomized parallel-group structure is important to interpretation. Participants were not assigned at random to the renal impairment and healthy groups; those groups represent different populations. The record notes intended comparability in selected demographic characteristics, but does not report whether it was achieved. This highlights a central distinction in clinical statistics: precise measurement of an outcome does not, by itself, make population groups exchangeable or establish that a group contrast is caused by the characteristic defining them.

The small planned enrollment also makes reporting of uncertainty particularly important. Without the group summaries, estimated contrast, and confidence interval, readers cannot determine how much information the primary endpoint provides. The absence of those results prevents assessment of both the observed magnitude and its precision. A planning illustration cannot replace this evidence, especially when the record does not give its numerical output or observed effect.

The safety entries illustrate another interpretive principle: participant counts are useful descriptive information but do not convey event type, timing, or comparative uncertainty. In a study with limited enrollment, the lack of recorded serious adverse events should not be generalized beyond the recorded observations. In combination, the design and reporting make clear why readers need outcome estimates and analysis details, not only a protocol description, to draw a statistical conclusion.

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 registry record does not report the primary AUC results, including group means, standard deviations, an estimated contrast, confidence interval, or p-value. This is the most direct limitation for interpreting the study’s central pharmacokinetic question. Without those statistics, the direction, magnitude, and precision of the comparison cannot be evaluated.

The study is non-randomized, open label, and uses groups defined by renal status. Although the summary describes intended comparability in age, gender, and body mass index, it does not report achieved group characteristics. The record also does not report adjustment for potential differences between groups. Thus, even if a primary contrast were available, it would need to be interpreted as an observational group comparison rather than as an isolated causal effect of renal status.

The registry does not report the detailed sampling schedule, the endpoint calculation procedure, or the operational definition of tau. It also does not report the analysis populations, missing-data handling, statistical model, or multiplicity strategy. These omissions limit assessment of whether the planned outcome was analyzed as intended and how robust any result would be.

The safety information is limited to participant counts. Event descriptions and timing are not reported, and death figures are not reported in the registry record. The record’s planning description does not include numerical planning outputs or the observed effect on which the illustrations are said to be based. No sample-size justification, interim-analysis information, or statistical analysis plan is reported in the registry record. These limits do not establish that the study had a particular flaw; they define what cannot be assessed from the available record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Pharmacokinetic of Single Dose of Pitavastatin 4 mg in Severe Renal Patients Versus Healthy Adult Volunteers — NCT01043094.
• Registry record last updated 2012-08-13; status last verified 2012-07.
• Results first posted 2012-08-13.
• 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

The registry describes a completed Phase 4, open-label, non-randomized, parallel-group study of a single oral dose of pitavastatin 4 mg. It compares adults with severe renal impairment who were not receiving hemodialysis with healthy adults. Enrollment is listed as 16, and the study summary describes 8 planned participants in each group. The record lists the study start as 2009-12 and primary completion as 2010-04.

The primary endpoint is AUC 0-t, a continuous measure reported in nanogram hour per milliliter, with a 48-hour timeframe. The registry does not report the primary endpoint results or statistical comparison. It records no serious adverse events among participants at risk in either group and records other adverse events in 3 participants in the renal impairment group and 1 in the healthy group. Event details and death figures are not reported.

The non-randomized design means group differences cannot automatically be attributed to renal status alone. Achieved demographic comparability, analysis methods, analysis populations, and missing-data procedures are not reported in the registry record. The central pharmacokinetic result therefore remains uninterpretable from the posted registry information.