Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab (NCT02275156), a na phase 1 study. The primary outcome is Maximum Observed Serum Concentration (Cmax) of Evolocumab.

2. Clinical Question

This question is descriptive and pharmacokinetic: it concerns measured serum concentrations after dosing, rather than a randomized comparison of clinical outcomes. The planned sampling extended from predose through 57 days postdose, with several postdose measurements. The registry also lists secondary outcomes involving adverse events, clinically relevant vital-sign or laboratory changes, anti-evolocumab antibodies, LDL-C area under the effect curve, and percent change in PCSK9. Numerical results for the primary pharmacokinetic endpoint are not reported in the registry record, so the posted information does not establish the size or precision of any difference among renal-function categories.

3. Trial Design

This was a completed Phase 1, open-label, single-dose study of evolocumab. The registry lists a single-group model and allocation as not applicable; it does not describe a randomized comparison. Participants received a single 140 mg subcutaneous dose on Day 1. Enrollment was 18. The study included participants with normal renal function, severe renal impairment, and end-stage renal disease requiring hemodialysis. The adverse-event record lists 6 participants at risk in each of those categories.

The main objective was to evaluate pharmacokinetics after dosing across the renal-function categories. Serum concentration sampling was specified at predose and 4 hours, then 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50, and 57 days postdose. Concentrations were measured using a validated enzyme-linked immunosorbent assay, with a lower limit of quantification of 800 ng/mL. The primary endpoint was maximum observed serum concentration, summarized as a mean with standard deviation.

The registry lists Amgen as sponsor and gives the study status as completed. The study start and primary completion dates are recorded as 2014-08-19 and 2014-12-19. The record does not report the protocol’s rationale for the enrollment target, the method used to assign participants to renal-function categories, or a prespecified statistical analysis plan. Because the study was not a randomized comparison, renal-category contrasts should be read as observational comparisons within this study rather than as estimates from randomized groups. The primary endpoint’s numerical results 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) analysis set (all participants for whom at least 1 PK parameter could be adequately estimated)

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 Maximum Observed Serum Concentration (Cmax) of Evolocumab, measured over Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose.

The primary endpoint was maximum observed serum concentration, or Cmax, of evolocumab. It represents the highest measured serum concentration among the scheduled observations for a participant. The registry specifies a mean and standard deviation as the summary statistics and defines the pharmacokinetic analysis set as participants for whom at least 1 pharmacokinetic parameter could be adequately estimated.

Cmax is used in pharmacokinetic assessment because it describes the observed peak concentration after dosing. Considering this measure across renal-function categories can help characterize whether the concentration profile differs among those groups. It is not, by itself, a clinical outcome, nor does it capture the full concentration-time profile. Other pharmacokinetic measures may describe exposure over time, but the primary endpoint named in the record is Cmax.

Serum samples were collected from predose through 57 days postdose at the times specified in the registry. The assay’s lower limit of quantification was 800 ng/mL. In general, an assay limit is important because values below that threshold cannot be quantified with the same precision as values within the assay’s measurable range. The record does not report how below-limit values were handled in the analysis.

Although the endpoint and its measurement approach are described, numerical Cmax estimates, standard deviations, confidence intervals, and results by renal-function category are not reported in the registry record. The endpoint definition therefore clarifies what was intended to be measured, but does not establish the observed concentration levels or the precision of an estimated contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary endpoint: maximum observed serum concentration of evolocumab, summarized as a mean with standard deviation. It does not report the numerical endpoint estimates, confidence intervals, p-values, or a statistical analysis plan. The explanations below describe general statistical concepts relevant to the stated endpoint and design; they do not imply that an unreported method was used.

What does the mean describe?

In general, a mean summarizes the central level of a continuous measurement across the participants included in an analysis. For this study, the specified measure is each participant’s maximum observed concentration, and the listed summary parameter is the mean. A mean can be useful for describing a group, but it does not show the spread of individual values or the shape of their distribution. It can also be influenced by unusually high or low observations. The registry record does not provide the group means, so the central concentration levels cannot be compared from the posted results.

What does the standard deviation add?

In general, the standard deviation describes how dispersed individual observations are around their mean. A small standard deviation indicates values are clustered more closely around the mean; a larger one indicates greater spread. It is a description of variability among observations, not a direct measure of uncertainty in the mean. The record names standard deviation as the dispersion measure but does not report its numerical values. Consequently, the amount of within-group variability in Cmax is not available from the registry record.

How is a confidence interval different?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a group mean or a difference between group means. Its width depends on features including the variability of observations and the amount of information available. A narrow interval indicates greater precision than a wide interval, while an interval that covers a range of materially different values signals uncertainty about the estimate. No confidence interval for the primary endpoint is reported in the registry record. Without one, the precision of the intended pharmacokinetic summary cannot be evaluated from the posted results.

What does the sampling schedule contribute?

Cmax depends on the observed concentration measurements and the times at which samples are collected. The record specifies predose sampling and measurements at 4 hours and at 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50, and 57 days postdose. In general, the observed maximum is the highest measured value, so it reflects both the underlying concentration profile and the sampling schedule. A maximum between scheduled measurements would not necessarily be directly observed. The record does not report the observed concentration-time data or any interpolation method.

Why does the assay limit matter?

The serum assay had a lower limit of quantification of 800 ng/mL. In general, results below an assay’s quantification limit may not be measurable with the same reliability as values above it. Analytic decisions about below-limit measurements can affect summaries, especially when such measurements occur repeatedly. The registry record does not report the number of below-limit results or their treatment, so no conclusion about their influence on Cmax can be drawn.

How should comparisons among renal categories be understood?

In general, randomization helps balance measured and unmeasured characteristics across comparison groups. This study is listed as single group, with allocation not applicable, and the registry explicitly notes that the renal categories are not a like-for-like control comparison. Thus, even if numerical category estimates were available, a difference would be descriptive unless supported by appropriate design and analysis. The record does not report adjustment methods, baseline comparability, or a statistical model for category contrasts.

What do planning illustrations mean?

Any sample-size planning illustrations associated with this study are planning exercises, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is to show a total number of events; for other outcomes, it is participants per arm. These assumptions do not establish that the original study used that design or that its enrollment was chosen using those calculations. The protocol’s own sample-size justification is not reported in the registry record. An illustration based on an observed effect is conditional on that effect and is not evidence that the study had a particular probability of detecting an effect.

The registry records 0 analyses. This means the posted record does not provide analysis-level statistical results for the primary endpoint in the registry record described. The stated endpoint and measurement procedures therefore support an explanation of the intended analysis target, but not a reconstruction of a model, an adjusted estimate, or a test of statistical significance.

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", "End Stage Renal Disease")
n   <- c(6, 6, 6)
m   <- c(21.3, 15.1, 11.7)
sp  <- c(9, 8.86, 7.2)
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  6  21.300  9.000  11.855  30.745
CARM  Severe Renal Impairment  6  15.100  8.860  5.802  24.398
CARM  End Stage Renal Disease  6  11.700  7.200  4.144  19.256

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and identifies the primary endpoint as maximum observed serum concentration. It also names secondary outcomes involving adverse events, clinically relevant vital-sign or clinical-laboratory changes, anti-evolocumab antibodies, LDL-C area under the effect curve from baseline to Day 57, and mean percent change in PCSK9. The posted record does not describe a hierarchy for testing these outcomes, an adjustment for multiple comparisons, or any other multiplicity strategy. Such procedures are not reported in the registry record.

Multiplicity is a general statistical concern when several outcomes or comparisons are examined: the chance of finding at least one apparently notable result can increase when many tests are conducted. Whether and how that concern was addressed in this study cannot be determined from the record. The registry lists 0 analyses, and numerical primary-endpoint results are not reported. No inference about statistical significance or confirmatory status should be made from outcome names alone.

The pharmacokinetic analysis set is described as all participants for whom at least 1 pharmacokinetic parameter could be adequately estimated. The record does not report how many participants met that definition, how many were excluded from the analysis, or the reasons for any exclusions. It also does not report missing sample counts, missing-data handling, deviations from the scheduled sampling times, or sensitivity analyses.

The record’s analysis-population definition is therefore useful but incomplete for evaluating selection and missingness. In general, excluding participants without adequate measurements can affect a summary if the ability to estimate a parameter is related to participant characteristics or concentration values. Whether that occurred is not reported in the registry record. The protocol’s statistical plan, including any multiplicity or missing-data procedures, is also not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperkalaemia (16.7%).

The registry separates serious adverse events from other adverse events and reports participants affected in each renal-function category. For serious adverse events, the record lists 0 affected among 6 at risk with normal renal function, 1 among 6 with severe renal impairment, and 0 among 6 with end-stage renal disease requiring hemodialysis. The overall serious-event figure is 1 affected among 18 at risk. These are descriptive counts; the record does not provide a comparative statistical analysis.

For other adverse events, the corresponding affected counts are 1, 1, and 2, with an overall figure of 4 among 18 at risk. The record lists hyperkalaemia as the top serious adverse-event term at 16.7%. The denominator used for that percentage, event details, timing, severity grading, and relationship to treatment are not reported in the registry record. The posted counts should not be treated as a complete account of event types or as evidence of a difference between categories. Death figures are not reported in the registry record; a missing death value should not be interpreted as a reported count of zero.

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

The study’s stated purpose was to assess evolocumab pharmacokinetics after a single subcutaneous dose in participants across three renal-function categories. The record defines maximum observed serum concentration as the primary endpoint, names the summary statistic, and describes the assay and sampling schedule. These details establish the intended measurement framework. However, the numerical primary endpoint results are not reported in the registry record, so the posted information does not show the observed Cmax in any category or the precision of an estimated contrast.

This absence limits what can be concluded statistically. It does not show that concentrations were the same across groups, that they differed, or that any observed difference was small or large. Without numerical estimates and uncertainty measures, the range of effects compatible with the data cannot be assessed. The record also does not report a statistical comparison or analysis plan for the endpoint.

The study is not a randomized comparison: it is listed as single group, allocation is not applicable, and the renal categories are not described as like-for-like control arms. Consequently, category contrasts would need to be interpreted cautiously even if estimates were available. The registry record does not provide the baseline information or adjustment methods needed to evaluate how participant characteristics may relate to any contrast.

The adverse-event counts are a separate descriptive part of the record and do not fill the gap in primary pharmacokinetic results. The reported serious and other adverse-event figures do not establish comparative safety, and the listed serious-event term lacks further denominator and event detail. The record also does not report the protocol’s statistical plan, missing-data approach, or sample-size justification. Overall, the posted information describes the study question and its measurement procedures, but does not provide enough numerical primary-endpoint evidence to quantify the pharmacokinetic findings.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a pharmacokinetic question framed around a measurable concentration endpoint and a defined sampling schedule. Maximum observed serum concentration is a direct summary of the highest measured concentration after dosing. Reporting its mean and standard deviation would describe both a group’s central level and variation among participants. The registry record specifies those measures but does not report their numerical results, which sharply limits interpretation of the primary question.

The renal-function categories also highlight a distinction between a planned group assessment and a randomized comparison. The record identifies a single-group model and no applicable allocation. Comparing categories can be useful descriptively, but it does not automatically isolate the effect of renal status from other characteristics that may differ among participants. Design, measured baseline information, and analysis methods all shape how a contrast should be interpreted; several of those details are not reported in the registry record.

The assay limit and sampling schedule are also relevant to interpretation. A concentration summary depends on when samples are collected and on how measurements near or below the quantification limit are handled. The registry reports the assay threshold and scheduled time points, but not the concentration data or the handling of below-limit values. That leaves key features of the observed data unavailable.

Finally, the record illustrates why a named endpoint is not equivalent to a reported result. A clear endpoint definition can explain what a study intended to estimate, while numerical estimates and uncertainty are needed to judge magnitude and precision. Here, the posted record supplies the design and measurement context and some adverse-event counts, but not the primary Cmax results or analysis-level statistics.

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 main limitation for statistical interpretation is that numerical results for the primary endpoint are not reported in the registry record. Group Cmax estimates, standard deviations, confidence intervals, and inferential comparisons are unavailable. The record also lists 0 analyses, so it does not provide a statistical analysis result from which to assess magnitude or precision.

The study is identified as open-label and single group, with allocation not applicable. The registry cautions that the renal categories are not a like-for-like control comparison. Any contrast among categories would therefore be descriptive unless supported by suitable analysis and context. Baseline characteristics, group comparability, and adjustment for potential confounding are not reported in the registry record.

The pharmacokinetic analysis set includes participants for whom at least 1 parameter could be adequately estimated, but the record does not state the number included in that set, exclusions, missing samples, or the reasons data may have been unavailable. The handling of measurements below the assay’s lower limit of quantification is also not reported. These omissions prevent assessment of how analytic inclusion and measurement limits may have affected the endpoint summaries.

Further limitations include the absence of a reported statistical analysis plan, multiplicity procedures, and sample-size justification. The record does not provide detailed results for the listed secondary outcomes. Adverse-event counts are descriptive, and the denominator and further details for the reported hyperkalaemia percentage are not given. These limitations restrict interpretation of both the pharmacokinetic question and the safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab — NCT02275156.
• Registry record last updated 2022-11-07; status last verified 2022-11.
• Results first posted 2016-01-29.
• 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 record describes a completed Phase 1, open-label, single-dose study of evolocumab in participants with normal renal function, severe renal impairment, or end-stage renal disease requiring hemodialysis. Participants received a single 140 mg subcutaneous dose on Day 1. The primary endpoint was maximum observed serum concentration, summarized as a mean with standard deviation. Serum samples were scheduled from predose through 57 days postdose and measured by a validated assay with a lower limit of quantification of 800 ng/mL.

Numerical primary-endpoint results and analysis-level statistics are not reported in the registry record. The record lists descriptive serious and other adverse-event counts, including hyperkalaemia at 16.7% as the top serious adverse-event term. Its single-group design does not support treating renal-category contrasts as randomized comparisons. Details of the statistical plan, missing-data handling, and sample-size justification are not reported in the registry record.