Efficacy, Safety and Pharmacokinetics of Sugammadex (Org 25969; MK-8616) at 3 Different Time Points After 0.6 mg/kg Esmeron® in Male Participants (P05940; MK-8616-020).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety and Pharmacokinetics of Sugammadex (Org 25969; MK-8616) at 3 Different Time Points After 0.6 mg/kg Esmeron® in Male Participants (P05940; MK-8616-020). (NCT03519854), a randomized phase 2 study. The primary outcome is Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9.

2. Clinical Question

3. Trial Design

This was a randomized, placebo-controlled, phase II, parallel-group trial. The registry labels the masking as double, while the official trial description calls the study assessor-blinded. It enrolled 99 participants and is listed as completed. The trial description identifies the participants as male subjects with ASA class 1 or 2 who were receiving surgery.

The treatment structure crossed five sugammadex doses—1, 2, 4, 6, and 8 mg/kg—with three administration times: 3, 5, or 15 minutes after 0.6 mg/kg Esmeron®. Placebo groups were included at each administration time. Each study treatment was described as a single intravenous bolus. This arrangement supports descriptive consideration of dose within each timing group, while keeping the post-Esmeron® administration time distinct.

The reported primary endpoint population was per protocol. It included randomized participants who received treatment, had no major protocol violations, and had data for the outcome. The number of participants contributing to the primary endpoint differed by arm, with reported group sizes from 3 to 6. These are outcome-specific counts and should not be conflated with the enrollment of 99.

The record identifies seven secondary outcomes, including heart rate and corrected QT interval at baseline and after study treatment, as well as participants experiencing an adverse event. The registry record does not report details such as the randomization sequence, allocation concealment, site count, or the intended sample-size justification. Although the trial is identified as multicenter in its official description, further operational details 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: One participant originally randomized to receive 2 mg/kg Sugammadex, given 3 minutes after Esmeron® (Arm C), incorrectly received placebo. As a result, this participant is counted as Started/Treated in the "Arm A. Placebo; given 3 minutes after Esmeron®" arm.

Only the first 6 of 18 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol, includes all randomized participants receiving study treatment without major protocol violations, having data available for this outcome measure.

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: Includes all randomized participants receiving study treatment. One participant randomized to receive 2 mg/kg Sugammadex, given 3 minutes after Esmeron® (Arm C), incorrectly received placebo. This participant is counted in the "Arm A. Placebo; given 3 minutes after Esmeron®" arm.

Only the first 6 of 19 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Mean Time From Start of Study Treatment Administration to Recovery of the T4/T1 Ratio to 0.9, measured over Up to 70 minutes following administration of study treatment.

The primary endpoint is the mean time, in minutes, from the start of study treatment administration until the participant’s T4/T1 ratio reached 0.9. T4 and T1 refer to the fourth and first thumb-twitch responses elicited by electrical stimulation of the ulnar nerve. The trial assessed the twitch response of the adductor pollicis muscle, applying the stimulation protocol repeatedly every 15 seconds. The endpoint was assessed for up to 70 minutes after study treatment.

The T4/T1 ratio is a measure of the degree of neuromuscular blockade: a value of 0 indicates loss of the T4 twitch, while a value of 1 indicates no neuromuscular blockade. Reaching 0.9 is the specified recovery threshold. As a result, elapsed time to that threshold gives a clinically interpretable measure of the speed of measured recovery, rather than a single measurement at a fixed time. A lower mean recovery time indicates that the threshold was reached sooner on average.

The endpoint is reported as a mean with a standard deviation. Means describe average recovery time in each arm; standard deviations describe the spread of individual times around those averages. They are not confidence intervals and do not, on their own, show how precisely an arm mean has been estimated. The registry describes the original time summaries as minutes:seconds and notes that they were reformatted into minutes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant has a recovery time measured in minutes, and the registry reports the mean and standard deviation in each arm. A mean is the arithmetic average of measured values. It provides a concise description of the group’s central value, but may be influenced by unusually long or short observations, especially when a group is small. The standard deviation describes how dispersed individual observations are around the mean. A larger standard deviation indicates more variation in observed times; it does not measure uncertainty in the mean in the same way as a confidence interval.

What would a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, such as an arm mean or a contrast between arms. Its width depends on the variability in the data and the amount of information available. A narrow interval indicates greater precision than a wide interval, under the assumptions of the method used. No confidence intervals are reported for the primary outcome in the registry record, so the precision of the arm means and of any between-arm contrast cannot be read directly from interval estimates.

What does the arm structure allow?

The trial has placebo and five active doses within each of three administration-time strata. Descriptive comparisons of means can therefore be made within a common timing stratum. However, observed differences between means do not by themselves provide a formal test of a dose effect, a timing effect, or an interaction between dose and timing. Such tests require an analysis plan and model, including decisions about which observations and contrasts to use. Those details are not reported in the registry record. The posted results list no analyses.

General statistical explanation: random assignment can help make groups comparable on average, but it does not remove random variation, and it cannot guarantee balance in small groups. With only 3 to 6 participants contributing to each primary-outcome arm, individual observations can have substantial influence on a group mean. This is one reason to consider group size and variability alongside the mean, and to avoid treating the observed ordering as a precise estimate of a dose-response relationship.

Why is variability important?

General statistical explanation: when variability is larger than expected under a simple statistical model, the data are sometimes described as over-dispersed. Over-dispersion matters because a model that assumes too little variability can produce standard errors that are too small and confidence intervals that are too narrow. The reported standard deviations provide a direct description of observed spread, but the registry record does not report a model-based assessment of over-dispersion or a modeling approach for the primary endpoint.

The endpoint was recorded by repeated stimulation every 15 seconds until the T4/T1 ratio reached 0.9, subject to assessment up to 70 minutes after study treatment. The record summarizes the outcome as a mean time, but does not report how participants who did not reach the threshold within the assessment period were handled. It also does not describe a time-to-event analysis. General statistical explanation: when an event may not be observed during follow-up, the analysis can need to account for censoring rather than treating every recorded time as an ordinary complete observation. Whether and how this issue arose or was addressed is not reported in the registry record.

The sample-size assumptions describe a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a fraction of the observed effect. Such illustrations are not the trial’s own design justification and are not observed power. The registry record does not report the trial’s sample-size justification, or the effect size and assumptions used when the trial was designed. No numerical planning outputs for this primary endpoint are stated in the record.

General statistical explanation: power is a property of a planned analysis under specified assumptions, not a retrospective measure of whether a result is true. Planning calculations can show how a hypothetical future study might be sized for a chosen effect and analysis, but those calculations do not change the amount of information collected in the completed trial. The primary endpoint results should therefore be interpreted from the actual group sizes, means, and standard deviations, together with the limits of the registry’s reporting.

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("Arm A. Placebo; Given 3 Minutes After Esmeron®", "Arm B. 1 mg/kg Sugammadex; Given 3 Minutes After E", "Arm C. 2 mg/kg Sugammadex; Given 3 Minutes After E", "Arm D. 4 mg/kg Sugammadex; Given 3 Minutes After E", "Arm E. 6 mg/kg Sugammadex; Given 3 Minutes After E", "Arm F. 8 mg/kg Sugammadex; Given 3 Minutes After E")
n   <- c(3, 6, 3, 6, 5, 5)
m   <- c(52.05, 22.73, 4.93, 6.25, 1.85, 1.83)
sp  <- c(8.77, 11.58, 1.25, 9, 0.62, 0.87)
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  Arm A. Placebo; Given 3 Minutes After Esmeron®  3  52.050  8.770  30.264  73.836
CARM  Arm B. 1 mg/kg Sugammadex; Given 3 Minutes After E  6  22.730  11.580  10.578  34.882
CARM  Arm C. 2 mg/kg Sugammadex; Given 3 Minutes After E  3  4.930  1.250  1.825  8.035
CARM  Arm D. 4 mg/kg Sugammadex; Given 3 Minutes After E  6  6.250  9.000  -3.195  15.695
CARM  Arm E. 6 mg/kg Sugammadex; Given 3 Minutes After E  5  1.850  0.620  1.080  2.620
CARM  Arm F. 8 mg/kg Sugammadex; Given 3 Minutes After E  5  1.830  0.870  0.750  2.910

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and seven secondary outcomes. The secondary measures include mean heart rate and mean corrected QT interval at baseline, 2 minutes after study treatment, and 30 minutes after study treatment, as well as the number of participants experiencing an adverse event. The record does not report how these outcomes were prioritized or how multiple statistical comparisons were to be handled.

Multiplicity arises when several outcomes, time points, doses, or pairwise comparisons are examined. General statistical explanation: testing many hypotheses can increase the chance of at least one apparently unusual result, even if no true effect exists. A prespecified strategy may define a primary contrast, adjust significance thresholds, or describe secondary results as exploratory. The registry record does not report a multiplicity strategy, and no inferential analyses are posted. There are consequently no posted adjusted p-values or confidence intervals to interpret.

The primary endpoint population was per protocol and required available outcome data, treatment receipt, and no major protocol violations. The arm-level primary outcome counts range from 3 to 6. The registry record does not report how many participants lacked primary-outcome data, why data might be missing, or how missing values were handled. It also does not report an intention-to-treat analysis or a sensitivity analysis comparing analysis populations.

These omissions matter because analysis-population decisions and missing-data assumptions can influence estimates. General statistical explanation: a complete-case summary describes participants with observed measurements, but can be unrepresentative if the availability of measurements is related to outcome or treatment. The record does not provide enough information to assess whether such a concern affected these results. Safety group denominators are reported separately from the primary-outcome counts, so the two sets of group sizes should not be assumed to represent the same analysis population.

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 serious-adverse-event counts are zero in every listed group, and deaths are also listed as zero in every group. The number at risk for serious adverse events varies by arm, from 3 to 6 participants. These are small denominators; zero observed serious events in these groups does not establish that the underlying risk is zero.

Non-serious adverse events were reported in several groups. For example, 5 participants were affected in the 1 mg/kg group administered 3 minutes after Esmeron®, and 4 were affected in each of the 4 mg/kg and 6 mg/kg groups at that same time point. At 15 minutes, 4 participants were affected in each of the 1 mg/kg and 2 mg/kg groups. These counts are descriptive; they do not account for event type, duration, severity, or differences in follow-up unless such information is separately reported. The registry lists no top serious adverse-event terms.

General statistical explanation: a count of participants with an event is not the same as a count of all events, since one participant can experience more than one event. The registry outcome is framed as the number of participants experiencing an adverse event. No comparative safety analysis or uncertainty interval is reported, so the figures should not be used as precise estimates of relative risk between doses or placebo.

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

The results describe time to a measured recovery threshold among participants included in the per-protocol primary-outcome population. Within each administration-time group, the reported sugammadex means are lower than the placebo mean. The pattern across the tested doses is broadly compatible with shorter average recovery times at higher doses, but some adjacent dose means are not ordered in a strictly decreasing sequence. The results therefore show a descriptive pattern, not a perfectly regular dose-response curve.

The endpoint has a defined physiological measurement and threshold: recovery of the T4/T1 ratio to 0.9. A lower observed mean time means participants reached that threshold sooner on average. This is not the same as showing that every participant recovered at the same speed, or that a group mean precisely predicts the result for an individual. Standard deviations show that individual recovery times varied, and the small arm sizes limit how confidently the means can be generalized beyond the participants observed.

No formal statistical comparisons are posted. There are no confidence intervals or p-values with which to assess the precision of differences or their compatibility with chance variation. The registry record also does not describe a model for dose, timing, or their joint effects. Consequently, the results should not be characterized as statistically significant, nor should a specific dose or timing schedule be declared superior on the basis of these summaries alone.

The safety record lists no serious adverse events or deaths in the treatment groups, alongside non-serious adverse-event counts that vary by group. Because the groups are small and comparative safety analyses are not reported, these observations do not establish the absence of risk or a reliable safety ranking. They describe what was recorded in this trial, within its reported follow-up and sample.

Overall, the registry results are useful as early, exploratory evidence about measured recovery times across several doses and administration times. They do not establish a definitive effect estimate, support broad conclusions about other populations, or provide a complete account of how all outcomes and missing data were analyzed.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it varies both dose and the interval between Esmeron® and study treatment. Keeping those dimensions distinct is important: a comparison across doses within one timing group addresses a different question from a comparison across timing groups at one dose. The design produces a structured set of descriptive observations that can inform hypotheses about dose and timing, but the registry results do not report formal tests of either dimension or their interaction.

The endpoint also illustrates the difference between measuring a process repeatedly and summarizing it as a single group mean. T4/T1 recovery was assessed every 15 seconds, while the reported outcome is elapsed time to a specified threshold. That definition makes the outcome interpretable, but the summary alone does not disclose each participant’s trajectory, the distribution of times, or how a participant who did not reach the threshold during assessment was handled.

Small groups make descriptive precision especially important. The primary-outcome sample sizes range from 3 to 6 per arm, and the standard deviations differ across arms. A mean can convey the observed central value, but without interval estimates or an analysis model, readers cannot judge the precision of a contrast from the registry results alone. This is a useful setting for separating an apparent pattern from a formally estimated treatment effect.

The record also highlights the role of transparent reporting. The trial reports a primary endpoint and secondary outcomes, but does not report a multiplicity strategy, a missing-data approach, or inferential analyses. Those details are necessary to understand how conclusions would be drawn across multiple doses, timings, and outcomes. The findings are therefore most informative as exploratory, arm-level summaries, with their analytic limits kept visible.

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 endpoint population is per protocol rather than all enrolled participants. It excludes randomized participants who did not receive treatment, had major protocol violations, or lacked data for the endpoint. The registry record does not report the number or characteristics of any excluded participants, the reasons for missing outcome data, or whether exclusions differed by group. This limits assessment of selection into the analyzed population.

Primary-outcome group sizes are small, ranging from 3 to 6 participants, and differ across arms. Standard deviations also vary. These features make the reported means sensitive to individual observations and leave limited information for assessing the reliability of dose or timing patterns. No confidence intervals or formal comparisons are posted.

The endpoint is observed over a stated period of up to 70 minutes, but the registry record does not report how observations were treated if the threshold was not reached during that period. It does not describe an analysis for censored times, distributions of recovery times, or a model accounting for the treatment-time structure. The lack of those details prevents evaluation of the assumptions behind any possible effect estimate.

The record does not report a multiplicity approach for the primary and secondary outcomes or the numerous dose and timing groups. It also does not report interim analyses, a statistical analysis plan, or a trial sample-size justification. These items are not available to clarify which comparisons were prespecified or how uncertainty was intended to be assessed.

The findings apply to the reported male surgical population with ASA class 1 or 2 and should not be assumed to represent other populations. The safety counts are based on small group denominators and include no posted comparative analysis. Together, these limitations favor cautious, descriptive interpretation of the registry results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy, Safety and Pharmacokinetics of Sugammadex (Org 25969; MK-8616) at 3 Different Time Points After 0.6 mg/kg Esmeron® in Male Participants (P05940; MK-8616-020). — NCT03519854.
• Registry record last updated 2019-04-02; status last verified 2019-03.
• Results first posted 2019-02-01.
• 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

NCT03519854 is a completed randomized, placebo-controlled, phase II parallel-group trial in male surgical participants with ASA class 1 or 2. It enrolled 99 participants and evaluated single intravenous bolus doses of sugammadex administered 3, 5, or 15 minutes after 0.6 mg/kg Esmeron®, with placebo groups at each time point.

The primary outcome was mean time from study-treatment administration to recovery of the T4/T1 ratio to 0.9, assessed by repeated nerve stimulation. The registry reports arm-level means and standard deviations for per-protocol groups of 3 to 6 participants. The observed sugammadex means were lower than placebo means within each timing stratum, although dose means were not strictly ordered at every step. No inferential analyses are posted.

Serious adverse-event and death counts are listed as zero across groups; non-serious adverse-event counts vary. The registry record does not report the missing-data approach, multiplicity strategy, or trial sample-size justification. These results are best read as exploratory descriptive observations rather than precise comparative estimates.