This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pharmacokinetics of Sugammadex (MK-8616) in Participants With Moderate and Severe Renal Insufficiency (MK-8616-105) (NCT02011490), a non-randomized phase 1 study. The primary outcome is Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02011490 |
| Phase | Phase 1 |
| Condition | Renal Insufficiency, Renal Impairment |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with moderate or severe renal insufficiency and healthy participants with normal renal function. The study enrolled 33 participants overall. The registry does not report the endpoint result values or provide the number analyzed for each pharmacokinetic group.
Intervention
A single 4 mg/kg intravenous dose of sugammadex. The study had two parts with different described administration setups: direct injection into a peripheral vein in Part 1, and administration through an IV catheter and tubing in Part 2.
Comparator
The pharmacokinetic question compares participants with moderate or severe renal insufficiency with participants who have normal renal function. This was a nonrandomized study, so the groups are not a like-for-like control comparison.
Primary question
How does the geometric least squares mean AUC from time zero to infinity for plasma sugammadex concentration differ across renal-function groups after a single intravenous dose? The registry describes the measure and method but does not report the group estimates or their confidence intervals.
The question is about pharmacokinetics: how plasma drug concentration changes over time and how much total exposure is represented by the area under that concentration-time curve. AUC from time zero to infinity combines the observed concentration profile with an estimate of the portion after the last measurable concentration. The registry describes measurement in the moderate and severe renal-insufficiency groups and in healthy controls.
The study is not a randomized trial of clinical outcomes. It does not establish that the groups were otherwise comparable, and it does not answer a treatment-benefit question. The reported primary endpoint is a continuous pharmacokinetic measure. Without the group estimates, confidence intervals, and analysis results, the direction and magnitude of any differences cannot be assessed from the registry record.
3. Trial Design
This was a Phase 1, open-label, nonrandomized, parallel study of sugammadex in participants with moderate or severe renal insufficiency and healthy controls. The registry lists total enrollment as 33 and the study status as completed. The recorded study dates are 2013-12-11 for start and 2014-06-06 for primary completion.
The brief description specifies a single 4 mg/kg intravenous dose and two study parts. In Part 1, the dose was described as an IV bolus into a peripheral vein. In Part 2, it was described as an IV bolus through an IV catheter connected to IV tubing with an injection port. The arm descriptions state that the bolus was administered over 10 seconds. Participants in Part 1 could also be enrolled in Part 2, which the registry says would reduce the overall number of participants enrolled.
The study included separate groups for severe renal insufficiency, moderate renal insufficiency, and healthy controls in each part. Because allocation was nonrandomized, renal-function status determined group membership rather than random assignment. The comparisons therefore describe pharmacokinetic measurements across these groups; they do not have the protection against confounding that random allocation can provide.
The primary pharmacokinetic analysis was conducted for Part 2 data. The registry states that Part 1 was not analyzed after review of drug-concentration data and dosing issues at investigative sites indicated that some participants may not have received the dose as intended. The specific completion of the registry’s explanation of the administration issue is not reported in the registry record. Consequently, the Part 1 groups should not be treated as contributing to the stated primary pharmacokinetic analysis.
The registry lists sugammadex as the intervention and describes no masking. Details of a formal sample-size justification, recruitment targets by renal-function group, or any interim analyses are not reported in the registry record. The stated planning illustration assumptions do not establish that those assumptions were used to design this study.
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: 33 subjects participated in study. 9 participated in both Part 1 and Part 2; for these, separate Part 2 baseline assessments were obtained. Due to differing Part 1 and Part 2 baseline renal function result, 1 participant was in severe renal insufficiency group in Part 1 and moderate renal insufficiency group in Part 2.
Part 1
| Stage | Severe Renal Insufficiency Participants: Part 1 | Moderate Renal Insufficiency Participants: Part 1 | Healthy Control Participants: Part 1 | Severe Renal Insufficiency Participants: Part 2 | Moderate Renal Insufficiency Participants: Part 2 | Healthy Control Participants: Part 2 |
|---|---|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 0 | 0 | 0 |
| COMPLETED | 8 | 8 | 8 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2
| Stage | Severe Renal Insufficiency Participants: Part 1 | Moderate Renal Insufficiency Participants: Part 1 | Healthy Control Participants: Part 1 | Severe Renal Insufficiency Participants: Part 2 | Moderate Renal Insufficiency Participants: Part 2 | Healthy Control Participants: Part 2 |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 6 | 6 | 6 |
| COMPLETED | 0 | 0 | 0 | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic analysis was performed only for Part 2 data for participants in Part 2. Analysis was not conducted for Part 1, as review of drug concentration data, and dosing issues noted at investigative sites, indicated that in some participants, doses may not have been administered directly into vein, and likely infiltrated surrounding tissue.
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: This table includes all 33 subjects who participated in study. Subjects who participated in both Part 1 and Part 2 are represented only once in this table. 1 participant was in severe renal insufficiency group in Part 1 and moderate renal insufficiency group in Part 2 and is allocated to severe renal insufficiency group in this table.
| Characteristic | Unit | Severe Renal Insufficiency Participants: Part 1 + Part 2 | Moderate Renal Insufficiency Participants: Part 1 + Part 2 | Healthy Control Participants: Part 1 + Part 2 | Total |
|---|---|---|---|---|---|
| Participants analysed | 10 | 11 | 12 | 33 | |
| Age, Continuous | Years | 62.3 (47 to 76) | 64.2 (47 to 76) | 58.3 (50 to 67) | 61.5 (47 to 76) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 5 | 8 |
| Sex: Female, Male: Male | Participants | 8 | 10 | 7 | 25 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Least Squares Mean Area Under the Plasma Drug Concentration-time Curve From Time Zero to Infinity (AUC0-∞) Following a Single IV Dose of Sugammadex, measured over For participants with: normal renal function - up to 48 hours post-dose (Part 1 + Part 2); moderate renal insufficiency - up to Day 28 (Part 1) or Day 10 (Part 2); severe renal insufficiency - up to Day 35 (Part 1) or Day 14 (Part 2).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ug*hr/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the geometric least squares mean area under the plasma drug concentration-time curve from time zero to infinity (AUC0-∞), following a single IV dose of sugammadex. It is a continuous pharmacokinetic measure, expressed in ug*hr/mL. AUC represents drug exposure across time: it uses the measured plasma concentration profile and includes an extrapolated contribution after the last measurable concentration.
The registry describes calculating the observed portion, AUC0-last, by the trapezoidal method. The extrapolated portion uses the estimated concentration at the last measurable time and the apparent first-order terminal elimination rate constant, λz. For each participant, λz was estimated by regression over the terminal log-linear portion of the plasma concentration-time profile. These steps are intended to account for both the observed measurements and the estimated terminal phase.
The reported group measure is a geometric least squares mean, obtained by back-transforming a least squares mean from an analysis of variance model applied to natural log-transformed AUC values. The associated 95% confidence interval describes uncertainty around that estimated group measure under the model. In general, confidence intervals help readers judge the precision of an estimate; they do not by themselves establish clinical importance.
AUC is used to characterize systemic exposure, not a clinical outcome. The registry record does not report the group estimates, confidence intervals, or a treatment-comparison result. Therefore, the endpoint definition can be explained, but the size and precision of any observed group differences cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies AUC0-∞ as the primary pharmacokinetic endpoint and specifies that its primary analysis used Part 2 data. However, it does not report the geometric least squares mean estimates for the renal-function groups or their 95% confidence intervals. Those result values are not reported in the registry record. It is therefore not possible to describe the direction, magnitude, or precision of the endpoint comparison from the registered information.
This absence matters for interpretation. A mean estimate would indicate the reported level of exposure in a group, while a confidence interval would show the uncertainty associated with that estimate under the stated model. Without either, readers cannot determine how close or far apart the group estimates were, how precise they were, or whether the data were compatible with a range of differences. No conclusion about the pattern of pharmacokinetic exposure across renal-function groups follows from the endpoint definition alone.
The design also limits how comparisons should be read. Participants were not randomized, and the comparison groups were defined by renal-function status. Any observed difference could reflect group characteristics in addition to renal function; the registry record does not describe adjustment for potential confounding beyond the stated model. The trial is thus a nonrandomized pharmacokinetic study, not a randomized efficacy comparison.
The study had two parts with different administration setups. The registry says that Part 1 was not included in the pharmacokinetic analysis after review of concentration data and site dosing issues raised concern that some doses may not have been administered directly as intended. The primary analysis is described as using Part 2 data only. This decision narrows the analysis population and means the Part 1 observations should not be combined with the stated primary analysis. Further details about the administration issue are not reported in the registry record.
Timeframes differed by group and part: normal renal function was followed up to 48 hours post-dose in Part 1 plus Part 2; moderate renal insufficiency up to Day 28 in Part 1 or Day 10 in Part 2; and severe renal insufficiency up to Day 35 in Part 1 or Day 14 in Part 2. Because the primary analysis used Part 2, the relevant endpoint timeframes for the renal-insufficiency groups were up to Day 10 and Day 14, respectively, while the normal-function timeframe was up to 48 hours. These are collection windows, not endpoint result values.
In general, interpretation of a pharmacokinetic comparison depends on the quality and completeness of concentration sampling, the appropriateness of the terminal-phase estimate, and the analysis model. The registry describes methods for calculating AUC and estimating group means, but it does not report diagnostics, sensitivity analyses, or enough outcome results to assess the robustness of the estimates. A statistical finding about exposure, even if reported, would not by itself establish a clinical benefit or harm. The registry record does not provide a clinical outcome comparison for that purpose.
The adverse-event counts are separate from the primary pharmacokinetic endpoint. The registry lists no serious adverse events in the reported groups, with group-specific numbers at risk, but it does not report death counts. Those safety entries do not supply evidence about the magnitude or precision of AUC differences. Overall, the registered design and methods identify what the investigators intended to measure, while the absence of endpoint estimates prevents a results-based interpretation of the central question.
9. Statistical Methods Explained
The registry describes a pharmacokinetic analysis of plasma sugammadex concentrations after one IV dose. A pharmacokinetic profile consists of concentration measurements collected at different times after dosing. The primary endpoint, AUC0-∞, uses those measurements to represent exposure over the interval from dosing through the estimated end of the concentration profile. It is a continuous outcome rather than a count or time-to-event outcome.
How is AUC0-∞ formed?
The registry says that the area from time zero to the last time point with a detectable plasma concentration, AUC0-last, was determined by the trapezoidal method. In general, the trapezoidal method approximates the area under a curve by joining successive observations and adding the areas between them. It uses the observed concentration-time data, so the result depends on when samples were collected and on the concentration measurements available.
The area after the last measurable concentration is extrapolated rather than directly observed. The registry describes that portion as the estimated concentration corresponding to the last measurable time divided by λz. The λz value is the apparent first-order terminal elimination rate constant, estimated for each participant by regression of the terminal log-linear portion of the concentration-time profile. In general, this extrapolation extends the observed profile using the estimated terminal decline. It adds an estimate, not a new observed concentration measurement. The registry does not report individual concentration profiles or enough results to assess how much of the total AUC was extrapolated.
Why use a geometric least squares mean?
The registry states that AUC values were natural log-transformed before analysis. In general, a log transformation can make a positively skewed continuous measure more suitable for a model that assumes a more regular residual distribution. It also changes the scale on which group differences are fitted. Back-transforming the least squares mean returns the reported estimate to the original AUC scale, producing the geometric least squares mean described in the registry.
The analysis used an analysis of variance model with fixed effects, according to the endpoint description. A least squares mean is a model-based estimate for a group, rather than necessarily the unadjusted arithmetic average of the observed values. A fixed-effect model estimates group means under its specified structure. The registry excerpt does not identify all model terms, covariates, or contrast definitions, so those details are not reported in the registry record.
What does the confidence interval convey?
The endpoint specifies a 95% confidence interval for the geometric least squares mean. In general, a confidence interval conveys statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates the range of values compatible with the data and model at the stated confidence level. It is not a probability statement that the true value lies within a particular realized interval.
The registry record does not report the actual intervals or group estimates. No precision judgment, group ranking, or comparison of effect size can therefore be made from the registered result information. A complete comparison would ordinarily require the estimated group values and the relevant contrast, with its uncertainty; those values are not reported in the registry record.
Why does the analysis population matter?
The registry says pharmacokinetic analysis was performed only for Part 2 data for participants in Part 2, and that Part 1 was not analyzed. The stated reason refers to review of drug-concentration data and dosing issues at investigative sites, with concern that some participants may not have received the dose directly into the intended route. The explanation is incomplete in the registry record, and additional details are not reported in the registry record. Excluding Part 1 means its measurements do not contribute to the stated primary analysis.
In general, an analysis population defines which participants contribute outcome information. This can affect how broadly a result applies and how much information supports an estimate. The registry does not report participant-level exclusions, the number with evaluable AUC data in each Part 2 group, or how missing concentration measurements were handled. These details are needed to understand the amount of information behind the analysis.
How should planning illustrations be read?
The stated planning assumptions describe a statistical illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect to detect is expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the calculated participant counts or the effect estimates needed to interpret those illustrations.
In general, a planning calculation estimates the sample size that would be required to detect a specified effect under stated assumptions. It does not show the probability that a completed study has established a finding, and it does not replace the observed estimate and its uncertainty. Since the endpoint result values are not reported in the registry record, the planning illustration cannot be interpreted as a substitute for the primary analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures and 6 analyses. The primary outcome is identified as geometric least squares mean AUC0-∞, but the registry does not report whether a multiplicity adjustment was used across outcomes, analyses, or comparisons. It also does not describe a hierarchy of hypotheses or a family-wise error approach. Those details are not reported in the registry record.
In general, when several statistical questions are tested, the chance of at least one false-positive finding can increase if each is interpreted without accounting for multiplicity. A prespecified hierarchy or adjustment can help control that risk. The existence of multiple listed outcomes alone does not establish that all were tested as confirmatory hypotheses, and the registry does not provide enough information to determine how they were treated.
The endpoint description says the primary pharmacokinetic analysis used Part 2 data only. Part 1 was not analyzed following review of drug-concentration data and dosing issues. The registry does not report a full analysis-population definition, participant flow by group, numbers with evaluable endpoint data, or the handling of missing concentration measurements. It also does not describe whether any imputation or sensitivity analysis was used. These analysis and missing-data details are not reported in the registry record.
In general, missing pharmacokinetic measurements can affect the area calculation, particularly when observations needed to characterize the terminal phase are unavailable. The registry explains how AUC was calculated when measurements were available, but it does not explain how incomplete profiles were handled or how many profiles were incomplete. Consequently, readers cannot assess the potential influence of missing data from the record alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Severe Renal Insufficiency Participants: Part 1 | 0 | 8 | 0.0% |
| Moderate Renal Insufficiency Participants: Part 1 | 0 | 8 | 0.0% |
| Healthy Control Participants: Part 1 | 0 | 8 | 0.0% |
| Severe Renal Insufficiency Participants: Part 2 | 0 | 6 | 0.0% |
| Moderate Renal Insufficiency Participants: Part 2 | 0 | 6 | 0.0% |
| Healthy Control Participants: Part 2 | 0 | 6 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Severe Renal Insufficiency Participants: Part 1 | 3 of 8 |
| Moderate Renal Insufficiency Participants: Part 1 | 2 of 8 |
| Healthy Control Participants: Part 1 | 2 of 8 |
| Severe Renal Insufficiency Participants: Part 2 | 1 of 6 |
| Moderate Renal Insufficiency Participants: Part 2 | 2 of 6 |
| Healthy Control Participants: Part 2 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Severe Renal Insufficiency Participants: Part 1 | Moderate Renal Insufficiency Participants: Part 1 | Healthy Control Participants: Part 1 | Severe Renal Insufficiency Participants: Part 2 | Moderate Renal Insufficiency Participants: Part 2 | Healthy Control Participants: Part 2 |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 1 of 8 | 0 of 8 | 0 of 8 | 1 of 6 | 1 of 6 | 0 of 6 |
| Paraesthesia oral | Gastrointestinal disorders | 1 of 8 | 0 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Injection site extravasation | General disorders | 0 of 8 | 1 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Injection site reaction | General disorders | 0 of 8 | 0 of 8 | 1 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Tooth infection | Infections and infestations | 0 of 8 | 1 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Contusion | Injury, poisoning and procedural complications | 0 of 8 | 0 of 8 | 1 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 0 of 8 | 0 of 8 | 0 of 8 | 0 of 6 | 1 of 6 | 0 of 6 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 1 of 8 | 0 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Dizziness | Nervous system disorders | 1 of 8 | 0 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
| Hypoaethesia | Nervous system disorders | 0 of 8 | 1 of 8 | 0 of 8 | 0 of 6 | 0 of 6 | 0 of 6 |
The registry reports serious adverse events separately for six groups: severe renal insufficiency, moderate renal insufficiency, and healthy controls in Part 1 and Part 2. It records 0 serious adverse events among 8 participants at risk in each of the three Part 1 groups, and 0 among 6 participants at risk in each of the three Part 2 groups. These are group-specific counts; they should not be added or converted into rates to interpret the primary pharmacokinetic endpoint.
The registry also lists other adverse events: 3 in the severe renal-insufficiency Part 1 group, 2 in the moderate renal-insufficiency Part 1 group, 2 in the healthy-control Part 1 group, 1 in the severe renal-insufficiency Part 2 group, 2 in the moderate renal-insufficiency Part 2 group, and 0 in the healthy-control Part 2 group. These counts are reported separately from serious adverse events and should not be mistaken for serious events.
Death counts are not reported in the registry record. The registry’s adverse-event entries are descriptive and do not provide a randomized comparison. In general, the absence of reported serious events in these groups does not establish that an event cannot occur, and the small group counts limit what can be inferred about uncommon events. These safety figures do not answer the primary question about AUC exposure.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study question, the stated endpoint, and the broad analysis method. It describes a single-dose pharmacokinetic comparison involving moderate and severe renal insufficiency and healthy controls, with the primary analysis limited to Part 2. It also identifies AUC0-∞ as a model-based measure of plasma exposure and explains how the endpoint was calculated.
What the registered information does not establish is the observed size or direction of any group difference. The geometric least squares mean estimates and 95% confidence intervals are not reported in the registry record. Without those values, it is not possible to say whether the groups had similar or different measured exposure, or how precisely any difference was estimated. The methods description cannot be used as a substitute for those results.
Even if the endpoint estimates were available, the design would still need to be considered. The study was nonrandomized and open-label, and renal-function groups were not assigned by randomization. The results would describe an association between group status and pharmacokinetic measurements in the analyzed participants, rather than an effect established by randomized allocation. Differences in participant characteristics or study conduct could also matter; the registry does not report enough detail to assess these possibilities.
The endpoint is pharmacokinetic, not a clinical outcome. AUC measures drug exposure over time and does not, by itself, establish a clinical benefit, harm, or treatment recommendation. The registry record does not provide a clinical-outcome comparison. The adverse-event counts are limited descriptive safety information and are not a substitute for a comparative clinical assessment.
The Part 1 analysis exclusion is also important: the primary pharmacokinetic analysis used Part 2 data only after concerns about concentration data and dosing issues. This means the stated endpoint analysis does not represent a combined analysis of both parts. The registry does not report sufficient detail to assess the consequences of that exclusion or the handling of missing endpoint data.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it illustrates the distinction between defining a pharmacokinetic endpoint and reporting evidence about that endpoint. The registry provides a detailed account of AUC0-∞, including the observed-area calculation, terminal-phase extrapolation, log transformation, model-based estimate, and confidence interval. Those methods clarify what the investigators intended to quantify. They do not, without the estimates and intervals, tell readers what the analysis found.
The study also highlights why analysis populations matter. Although the design included two parts and groups with different renal-function status, the stated primary pharmacokinetic analysis was restricted to Part 2. The registry gives a reason involving concentration-data review and dosing issues, but the details of the issue and its impact are not reported in the registry record. An analysis decision based on data quality can be important, but readers need clear reporting of who was included and what data contributed to each estimate to judge its consequences.
Nonrandomized comparisons are common in descriptive pharmacokinetic questions, but they require careful interpretation. Participants are grouped by renal-function status rather than randomly assigned to those categories. Statistical modeling can estimate group means, but it cannot by itself remove all differences between groups unless relevant factors are measured and appropriately addressed. The registry does not specify enough model detail to assess that issue.
Finally, the listed planning assumptions demonstrate the difference between a planning illustration and an observed result. A sample-size calculation is conditional on its assumed effect and analysis approach; it is not observed power and cannot replace estimates with uncertainty. Here, the registry record does not report the endpoint results or the numerical planning outputs, so neither can be used to characterize the evidence for a group difference.
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 most direct limitation for interpretation is that the primary endpoint estimates and confidence intervals are not reported in the registry record. The study’s central pharmacokinetic comparison therefore cannot be described in terms of magnitude, direction, or precision. The endpoint method is documented, but the result needed to answer the question is absent.
The study was nonrandomized and open-label. Group membership reflected renal-function status rather than random assignment, so the comparison does not have the balance that randomization is intended to create. The registry does not report sufficient participant characteristics or model details to assess whether other group differences were considered in the analysis.
The primary analysis used Part 2 data only. The registry says Part 1 was not analyzed following review of concentration data and site dosing issues, but its explanation of the administration concern is incomplete. The record does not report the number of participants with usable endpoint data by group, the participant-level reasons for exclusion, or sensitivity analyses that might show how the exclusion affected results.
The registry also does not report missing-data methods, detailed model terms, diagnostics for the terminal-phase regression, or the share of AUC based on extrapolation. Such information would help readers judge the reliability of the model-based endpoint. The follow-up windows differed across groups and parts, and the Part 2 windows were not identical across renal-insufficiency groups and healthy controls.
Finally, the safety counts are descriptive, and deaths are not reported in the registry record. The record does not describe a multiplicity strategy or provide numerical sample-size illustration outputs. These omissions limit assessment of the statistical plan and the breadth of evidence, in addition to the lack of endpoint results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of Sugammadex (MK-8616) in Participants With Moderate and Severe Renal Insufficiency (MK-8616-105) — NCT02011490.
- Registry record last updated 2018-10-02; status last verified 2018-09.
- Results first posted 2015-02-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed Phase 1, open-label, nonrandomized, parallel study of a single 4 mg/kg IV dose of sugammadex in participants with moderate or severe renal insufficiency and healthy controls. Enrollment was 33. The study had two parts with different administration setups, and participants in Part 1 could also enroll in Part 2.
The primary endpoint was geometric least squares mean AUC0-∞ for plasma sugammadex concentration. The registry describes calculation by trapezoidal integration plus terminal-phase extrapolation, followed by analysis of natural log-transformed values and back-transformation. The stated primary pharmacokinetic analysis used Part 2 data only; Part 1 was not analyzed after review raised concerns about concentration data and dosing.
Group estimates and confidence intervals for the primary endpoint are not reported in the registry record. Serious adverse events were recorded as 0 in each of the six reported groups; death counts are not reported in the registry record.