A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED) (NCT01104545), a randomized phase 1 study. The primary outcome is Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants.

2. Clinical Question

The study is titled as a single-dose investigation of MK-3614 and names safety, tolerability, pharmacokinetics, and pharmacodynamics as its aims. The primary result available for interpretation is specifically the percentage with one or more adverse events among the eligible healthy participants. It does not summarize the pharmacokinetic or pharmacodynamic results, and it does not answer the primary endpoint question for the hypertensive participants.

The registry record describes a randomized, double-masked Phase 1 study and lists both MK-3614 and placebo. Its arm descriptions include repeated dosing periods with washout periods in the healthy panels, so the specific dosing arrangements are more complex than a simple one-time comparison between two groups. Further details about the allocation procedure and the analysis accounting for those arrangements are not reported in the registry record.

3. Trial Design

The registry record identifies NCT01104545 as a completed, randomized, double-masked, Phase 1 study with a parallel model. Its stated purpose was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-3614. The record lists an enrollment of 24 and the condition hypertension. It gives a study start of 2008-11-01 and a primary completion of 2009-05-01.

There are three described panels: healthy participants in Panels A and B, and hypertensive participants in Panel C. The healthy panels include several MK-3614 regimens and matching placebo. The arm descriptions mention multiple dosing periods and at least a 7-day washout between periods. Panel A includes a 0.25 mg dose with food; the record says other doses were administered after an 8-hour fast, although the food-administration description is truncated. Panel C lists MK-3614 and placebo regimens for hypertensive participants. The full dosing details for some arms are not reported in the registry record.

The primary endpoint is reported for healthy participants in Panels A and B who received at least one dose and had available endpoint data. Results are grouped by dose taken at the time of an adverse event, rather than presented as a single overall proportion for each person across all periods. The endpoint timeframe is up to 7 days for each dose level.

The record lists 28 outcome measures and 10 posted secondary results. Only two secondary continuous outcomes have numerical summaries and recalculated comparisons in the statistical information analyzed. A complete protocol, detailed randomization and masking procedures, and the full analysis plan are not reported in the registry record. Although the record labels the study parallel, the multi-period descriptions mean that the relationship between the model label and dosing periods cannot be clarified from the available 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: Each period of each panel (with exception of 0.25 mg fasted/fed periods) will be re-randomized to receive either study drug or placebo, i.e., a participant could be assigned to receive study drug in one period and placebo in another. The same participants will receive 0.25 mg MK-3614 in a fasted and fed state.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

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 Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants, measured over up to 7 days for each dose level.

The primary endpoint is the percentage of eligible healthy participants who reported one or more adverse events. The record defines an adverse event broadly as an unfavorable or unintended sign, symptom, disease, or abnormal laboratory finding temporally associated with use of a medicinal product, whether or not it was considered related to that product. Thus, this endpoint counts events reported during treatment without requiring investigators to judge that MK-3614 caused them.

The endpoint is summarized by dose taken at the time of the event and covers up to 7 days for each dose level. This gives a descriptive account of how often at least one event was reported in the dose groups. It does not describe the number, type, severity, or duration of events, nor does it distinguish events judged treatment-related from those not judged related in the posted primary result.

Adverse-event reporting is commonly used in early-phase studies to characterize tolerability and identify events that warrant closer attention in later research. In general, a percentage is easier to interpret when its denominator and follow-up period are clear; the registry identifies the endpoint population and per-dose timeframe. However, these small dose-group summaries are imprecise, and the record does not provide confidence intervals for the percentages or a formal comparison for this endpoint. The values should therefore be read as descriptions of the observed groups, not as precise estimates of event frequency in a broader population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary result is a binary percentage: for each reported dose group, it states the proportion of participants with at least one adverse event. In general, a binary outcome reduces each participant's experience to whether the defined event occurred at least once during the relevant observation period. This is useful for a straightforward frequency description, but it does not retain information about how many events a participant experienced or their clinical seriousness. The separate serious-event reporting addresses a different safety category.

The primary values are presented by dose level and panel, and the record says events are assigned to the dose being taken at the time. This matters because the healthy panel descriptions include multiple dosing periods. In general, repeated periods can create within-participant dependence: observations from the same person are not necessarily statistically independent. The registry record does not report how any such dependence was handled in an inferential analysis. No primary-endpoint hypothesis test or confidence interval is posted, so the percentage summaries should not be treated as adjusted comparisons.

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A wider interval indicates less precision, while a narrower interval indicates greater precision. For the recalculated augmentation-index comparison, the interval is reported as 95% and accompanies a mean difference; it describes uncertainty in that difference under the simple comparison used for the recalculation. It does not account for unreported design features or multiple testing. No confidence intervals are reported for the primary adverse-event percentages.

How should the recalculated comparisons be read?

The secondary comparisons are labelled recalculated because they use the posted summary statistics for an unadjusted comparison of group means. The augmentation-index comparison uses the 0.75 mg group and placebo, and the cyclic GMP comparison uses the same named dose and placebo. These calculations are not sponsor-reported analyses. They do not incorporate covariate adjustment, a repeated-measures model, or any other analysis method that is not specified in the registry record. The sponsor's own analysis takes precedence when a discrepancy is flagged; no discrepancy is flagged for the available comparisons, but sponsor-reported analyses are not listed.

For the augmentation-index comparison, the recalculated mean difference is -3.8, with a 95% confidence interval from -6.976 to -0.624 and an unadjusted p-value of 0.019. The sign indicates that the posted mean for the MK-3614 group is lower than the placebo mean under the subtraction used in the recalculation. A p-value measures how compatible the observed data are with a specified null hypothesis under the analysis assumptions; it is not the probability that the null hypothesis is true, nor does it quantify clinical importance. The result is unadjusted, and the registry's approach to multiplicity is not reported.

The cyclic GMP comparison has a recalculated mean difference of 0.0, a 95% confidence interval from -0.082 to 0.082, and an unadjusted p-value of 1.0. The summaries also show no posted participants for the 0.5 mg group for that outcome. This illustrates why the available results need to be read outcome by outcome: missing information in one dose group limits what can be compared, while a recalculated result based on the remaining group summaries does not resolve that missingness.

What do the planning illustrations mean?

A planning illustration is not observed power and does not describe what the study achieved. For the augmentation-index comparison, the record gives a calculation under a two-sided significance level of 0.05, equal allocation, and a normal approximation. It shows participants per arm for 80% power and participants per arm for 90% power when planning for 100%, 75%, or 50% of the observed effect. In general, planning calculations depend on assumptions about the effect to detect and the analysis; a value derived from an observed effect is not independent evidence that the effect is stable or reproducible. The illustration is not a sample-size justification for this trial, and its planning assumptions are not reported as the trial's design assumptions.

More broadly, the sample sizes in this study are small, and several estimates have no posted uncertainty measures. The registry record does not report a formal statistical analysis plan, a sample-size justification, interim analyses, or the handling of missing data for the primary endpoint. These omissions limit assessment of whether the posted summaries follow a prespecified analysis and how robust any comparison would be to alternative methods.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("0.25 mg MK-3614 Panel A", "1.25 mg MK-3614 Panel A", "0.25 mg w/ Food MK-3614 Panel A", "0.75 mg MK-3614 Panel A", "Placebo Panel A", "0.5 mg MK-3614 Panel B")
n      <- c(6, 6, 5, 6, 6, 6)
events <- c(6, 6, 4, 2, 4, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  0.25 mg MK-3614 Panel A  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  1.25 mg MK-3614 Panel A  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  0.25 mg w/ Food MK-3614 Panel A  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  0.75 mg MK-3614 Panel A  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Placebo Panel A  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1
ARM  0.5 mg MK-3614 Panel B  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy. It lists 28 outcome measures and 10 posted secondary results, while the numerical secondary analyses include unadjusted comparisons. When several endpoints, dose groups, and comparisons are examined, interpreting an isolated p-value without knowing the prespecified testing hierarchy or any adjustment can overstate how compelling that result is. It is not reported whether the trial designated a hierarchy among secondary outcomes or how multiplicity was addressed.

Missing-data handling is also not reported in sufficient detail to assess the analysis. The primary endpoint population is described as participants in Panels A and B who received at least one dose and had available endpoint data, but the registry does not explain how unavailable data were handled or whether exclusions occurred. The cyclic GMP summaries include a 0.5 mg group with no participants and no reported mean or standard deviation. The reason for the missing result is not reported in the registry record. The absence of a value should not be interpreted as a zero effect.

The primary outcome's analysis population is restricted to healthy participants in Panels A and B. Serious adverse events are reported for groups in all three panels, including the hypertensive panel. These populations answer different questions, and the primary percentages should not be generalized to the hypertensive group. The record does not report a formal analysis population definition for the secondary endpoints beyond the information in their outcome descriptions.

Finally, the registry does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses. It is therefore not possible to establish from the record whether the outcome definitions, comparisons, missing-data approach, and multiplicity handling were set in advance. These gaps do not invalidate the descriptive numbers, but they limit conclusions based on inferential comparisons.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event record lists 0 serious adverse events in each reported group and 0 deaths in each reported group. This includes the healthy dose groups and placebo groups in Panels A and B, as well as the MK-3614 and placebo groups in Panel C. The number at risk is reported separately for each group, with values ranging from 5 to 8 across the listed groups.

These entries mean that no serious adverse events or deaths were recorded in the posted group summaries during the reported study period. They do not establish that the risk of a serious event is zero. With small groups and limited observation, uncommon events may not occur in the study even if they could occur in a larger or longer study. The registry record does not provide confidence intervals for these serious-event figures or further detail on the observation period for them.

Serious adverse events are distinct from the primary endpoint, which includes any adverse event meeting the broad definition, whether or not it was considered related to study drug. The fact that serious-event counts are zero does not mean that no adverse events occurred. The primary endpoint summaries report nonzero percentages in every listed healthy dose and placebo group.

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

The posted results describe adverse-event reporting and selected secondary measurements during a small Phase 1 study of MK-3614. The primary endpoint is a per-dose percentage of healthy participants reporting at least one adverse event, with observation up to 7 days for each dose level. The values vary across dose groups and placebo groups, and the registry does not provide inferential comparisons or confidence intervals for those percentages. They are descriptive observations rather than precise estimates of risk.

The secondary information permits limited exploration of selected pharmacodynamic outcomes. The recalculated augmentation-index comparison is unadjusted and is not a sponsor-reported analysis. It should not be treated as definitive evidence, especially because the multiplicity strategy is not reported. Other listed outcomes do not all have numerical summaries available, and the posted secondary information does not provide a complete account of the study's pharmacokinetic or pharmacodynamic findings.

The results do not establish that MK-3614 does or does not improve a clinical outcome, and the registry does not report a clinical efficacy endpoint in the primary result. The adverse-event endpoint also does not establish causality: the record's definition includes events regardless of whether they were considered related to the medicinal product. Nor do zero serious adverse events or deaths establish the absence of risk.

The trial includes healthy participants and a hypertensive panel, but the primary endpoint is reported only for healthy participants. The primary percentages therefore cannot be applied directly to the hypertensive participants. Small group sizes, missing secondary results, unreported analysis details, and limited follow-up information constrain broader interpretation. The study is best understood as an early-phase description of selected safety and pharmacodynamic observations, not as a definitive assessment of clinical benefit or uncommon harms.

14. Why This Trial Matters Statistically

This study illustrates why early-phase results need to be interpreted at the level of the endpoint and population actually reported. The primary safety result is a set of percentages by dose group, rather than a single estimate for all participants or a formal comparison between MK-3614 and placebo. The panel structure and multiple dosing periods also make it important to distinguish the registry's model label from the details of the listed regimens.

It also shows how sparse data affect precision. The primary group sizes are small, and the registry provides no confidence intervals for those percentages. The pattern varies across the listed groups, so a simple dose-response narrative would not be supported by these summaries. Zero serious adverse events and deaths are useful descriptive details, but they cannot establish that uncommon events are absent.

For secondary results, recalculation from group summaries can offer a transparent exploratory comparison when sponsor analyses are not posted. Such calculations remain limited by the available data and assumptions. An unadjusted p-value does not address the multiplicity of outcomes, and a planning illustration based on an observed effect is not observed power or a justification for the original study size.

Finally, this record demonstrates the value of complete reporting. A formal analysis plan, fuller outcome results, an account of missing data, and clarification of how repeated periods were handled would make the results easier to evaluate. Without those details, the strongest conclusions are descriptive and bounded to the populations and measurements reported.

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 applies only to eligible healthy participants in Panels A and B. Although the trial includes a hypertensive panel, primary adverse-event percentages for that panel are not posted as part of this endpoint. The primary summaries are grouped by dose at the time of an event, and the registry does not describe how multiple dosing periods were handled statistically.

The groups are small, and the record gives no confidence intervals or formal comparisons for the primary percentages. It also does not provide adverse-event types, severity, duration, or the number of events per participant in the primary result. The broad endpoint definition includes events regardless of whether they were judged related to treatment, limiting causal interpretation.

Only selected secondary results have numerical summaries available. Some listed outcomes lack posted numerical results, and the cyclic GMP summary for the 0.5 mg group has no data. Reasons for missing results are not reported in the registry record. The secondary comparisons are unadjusted recalculations from posted summaries, with no sponsor-reported analyses listed and no multiplicity strategy reported.

The record does not report a detailed protocol or statistical analysis plan, a sample-size justification, interim analyses, or a full account of missing-data handling. The study model is labelled parallel, while healthy-panel descriptions refer to multiple dosing periods and washouts; the record does not explain the analysis implications of this arrangement. Follow-up for the primary endpoint is stated as up to 7 days per dose level, but this limited timeframe cannot characterize longer-term outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED) — NCT01104545.
• Registry record last updated 2019-08-08; status last verified 2019-06.
• Results first posted 2019-08-08.
• 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

NCT01104545 is a completed, randomized, double-masked Phase 1 study of single-dose MK-3614, with a parallel model listed in the registry. The record lists an enrollment of 24 and describes healthy participants in Panels A and B and hypertensive participants in Panel C. MK-3614 regimens and matching placebo are listed across the panels.

The primary endpoint is the percentage of healthy participants in Panels A and B reporting at least one adverse event, up to 7 days for each dose level. The posted percentages vary across dose and placebo groups; the registry does not provide a formal primary comparison or confidence intervals. The serious adverse-event summaries list 0 serious adverse events and 0 deaths in every reported group.

The record lists 28 outcome measures and 10 posted secondary results. Numerical summaries available for selected secondary outcomes support only limited, unadjusted recalculations. The multiplicity approach, detailed analysis plan, sample-size justification, and handling of missing data are not reported in the registry record.